Integrative Therapies for Low Back Pain That Include Complementary and Alternative Medicine Care: A Systematic Review

PubMed Central

Rose, Kevin; Kadar, Gena E.

2014-01-01

Study Design: Systematic review of the literature. Objective: To evaluate whether an integrated approach that includes different Complementary and Alternative Medicine (CAM) therapies combined or CAM therapies combined with conventional medical care is more effective for the management of low back pain (LBP) than single modalities alone. Summary of Background Data: LBP is one of the leading causes of disability worldwide, yet its optimal management is still unresolved. Methods: The PRISMA Statement guidelines were followed. The Cochrane Back Review Group scale was used to rate the quality of the studies found. Results: Twenty-one studies were found that met the inclusion criteria. The CAM modalities used in the studies included spinal manipulative therapy, acupuncture, exercise therapy, physiotherapy, massage therapy, and a topical ointment. Twenty studies included acupuncture and/or spinal manipulative therapy. Nine high quality studies showed that integrative care was clinically effective for the management of LBP. Spinal manipulative therapy combined with exercise therapy and acupuncture combined with conventional medical care or with exercise therapy appears to be promising approaches to the management of chronic cases of LBP. Conclusions: There is support in the literature for integrated CAM and conventional medical therapy for the management of chronic LBP. Further research into the integrated management of LBP is clearly needed to provide better guidance for patients and clinicians. PMID:25568825

The FIND-CKD study--a randomized controlled trial of intravenous iron versus oral iron in non-dialysis chronic kidney disease patients: background and rationale.

PubMed

Macdougall, Iain C; Bock, Andreas; Carrera, Fernando; Eckardt, Kai-Uwe; Gaillard, Carlo; Van Wyck, David; Roubert, Bernard; Cushway, Timothy; Roger, Simon D

2014-04-01

Rigorous data are sparse concerning the optimal route of administration and dosing strategy for iron therapy with or without concomitant erythropoiesis-stimulating agent (ESA) therapy for the management of iron deficiency anaemia in patients with non-dialysis dependent chronic kidney disease (ND-CKD). FIND-CKD was a 56-week, open-label, multicentre, prospective, randomized three-arm study (NCT00994318) of 626 patients with ND-CKD and iron deficiency anaemia randomized to (i) intravenous (IV) ferric carboxymaltose (FCM) at an initial dose of 1000 mg iron with subsequent dosing as necessary to target a serum ferritin level of 400-600 µg/L (ii) IV FCM at an initial dose of 200 mg with subsequent dosing as necessary to target serum ferritin 100-200 µg/L or (iii) oral ferrous sulphate 200 mg iron/day. The primary end point was time to initiation of other anaemia management (ESA therapy, iron therapy other than study drug or blood transfusion) or a haemoglobin (Hb) trigger (two consecutive Hb values <10 g/dL without an increase of ≥ 0.5 g/dL). The background, rationale and study design of the trial are presented here. The study has been completed and results are expected in late 2013. FIND-CKD was the longest randomized trial of IV iron therapy to date. Its findings will address several unanswered questions regarding iron therapy to treat iron deficiency anaemia in patients with ND-CKD. It was also the first randomized trial to utilize both a high and low serum ferritin target range to adjust IV iron dosing, and the first not to employ Hb response as its primary end point.

Rifampicin versus streptomycin for brucellosis treatment in humans: A meta-analysis of randomized controlled trials.

PubMed

Meng, Fanjie; Pan, Xiangpo; Tong, Wenzhen

2018-01-01

Brucellosis is a zoonotic disease with a high morbidity in developing countries, but there the optimal treatment is not yet determined. Therefore, the development of a simple and effective treatment is important. The aim of this study was to summarize the available evidences and compare rifampicin with streptomycin in human brucellosis with doxycycline as background regimen. We systematically searched PubMed, EmBase, and the Cochrane Library from their inception up through December 2016. We included studies with a randomized controlled design that evaluated the effect of streptomycin compared with rifampicin in human brucellosis patients who received doxycycline therapy as background regimen. The overall failure and relapse were summarized using random-effects model. Our meta-analysis included 1,383 patients with brucellosis from 14 trials. We found that patients who received rifampicin therapy had a higher risk of overall failure (RR: 2.36; 95% CI: 1.72-3.23; P<0.001) and relapse (RR: 2.74; 95% CI: 1.80-4.19; P<0.001) compared with streptomycin. Results of the sensitivity analysis were consistent with the overall analysis. Subgroup analysis indicated that mean age of the patients and percentage of male participants might influence the treatment effects. Furthermore, no publication bias was detected. The findings of this study indicated that rifampicin therapy significantly increased the risk of overall failure and relapse compared with streptomycin. Hence, it can be recommended to patients with human brucellosis receiving streptomycin therapy.

Recurrent pericarditis: a case report and literature review

PubMed Central

Katinaitė, Justina; Petrauskienė, Birutė

2017-01-01

Background. Recurrence affects about 30% (20% to 50%) of patients within 18 months after the initial episode of acute pericarditis resulting in subsequent rehospitalizations. Bearing in mind high treatment costs of patients admitted to hospital with acute and recurrent pericarditis, there is a need to optimize the treatment of both of these conditions. Materials and methods. We present a case of recurrent pericarditis. The first episode of pericarditis was diagnosed in 2006. Three months later the patient was hospitalized due to clinical symptoms suggesting recurrence of a past condition. Ten years after the initial episode of acute pericarditis the patient was hospitalized for the treatment of recurrent pericarditis. The search for etiology of the disease was unsuccessful, the patient received treatment with nonsteroidal anti-inflammatory drugs; empiric antimicrobial therapy was also administered. Results and conclusions. Acute pericarditis is the most common disease of the pericardium encountered in clinical practice. Colchicine has been demonstrated as a first-line drug to be added to conventional anti-inflammatory therapies in patients with a first episode of pericarditis or its recurrences in order to improve the response to therapy and reduce recurrences. Despite a large amount of new data, there are still several issues that require additional research and clarification, including the search for new individualized therapies, the best duration of treatment for patients with pericardial diseases, and optimization of patient follow-up in order to collect data on long-term outcomes that would allow shortening the duration of in-patient treatment and reduction of recurrences. PMID:29217970

Antimicrobial Photodynamic Therapy Combined With Conventional Endodontic Treatment to Eliminate Root Canal Biofilm Infection

PubMed Central

Garcez, Aguinaldo S.; Ribeiro, Martha S.; Tegos, George P.; Núñez, Silvia C.; Jorge, Antonio O.C.; Hamblin, Michael R.

2011-01-01

Background and Objective To compare the effectiveness of antimicrobial photodynamic therapy (PDT), standard endodontic treatment and the combined treatment to eliminate bacterial biofilms present in infected root canals. Study Design/Materials and Methods Ten single-rooted freshly extracted human teeth were inoculated with stable bioluminescent Gram-negative bacteria, Proteus mirabilis and Pseudomonas aeruginosa to form 3-day biofilms in prepared root canals. Bioluminescence imaging was used to serially quantify bacterial burdens. PDT employed a conjugate between polyethylenimine and chlorin(e6) as the photosensitizer (PS) and 660-nm diode laser light delivered into the root canal via a 200-µ fiber, and this was compared and combined with standard endodontic treatment using mechanical debridement and antiseptic irrigation. Results Endodontic therapy alone reduced bacterial bioluminescence by 90% while PDT alone reduced bioluminescence by 95%. The combination reduced bioluminescence by >98%, and importantly the bacterial regrowth observed 24 hours after treatment was much less for the combination (P<0.0005) than for either single treatment. Conclusions Bioluminescence imaging is an efficient way to monitor endodontic therapy. Antimicrobial PDT may have a role to play in optimized endodontic therapy. PMID:17066481

Free terminal time optimal control problem of an HIV model based on a conjugate gradient method.

PubMed

Jang, Taesoo; Kwon, Hee-Dae; Lee, Jeehyun

2011-10-01

The minimum duration of treatment periods and the optimal multidrug therapy for human immunodeficiency virus (HIV) type 1 infection are considered. We formulate an optimal tracking problem, attempting to drive the states of the model to a "healthy" steady state in which the viral load is low and the immune response is strong. We study an optimal time frame as well as HIV therapeutic strategies by analyzing the free terminal time optimal tracking control problem. The minimum duration of treatment periods and the optimal multidrug therapy are found by solving the corresponding optimality systems with the additional transversality condition for the terminal time. We demonstrate by numerical simulations that the optimal dynamic multidrug therapy can lead to the long-term control of HIV by the strong immune response after discontinuation of therapy.

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

PubMed Central

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

2015-01-01

Background Bevacizumab is an exogenous inhibitor which inhibits the biological activity of human VEGF. Several studies have investigated the effectiveness of bevacizumab therapy according to different cancer types but these days there is an intense debate on its utility. We have investigated different methods to find the best tumor volume estimation since it creates the possibility for precise and effective drug administration with a much lower dose than in the protocol. Materials and Methods We have examined C38 mouse colon adenocarcinoma and HT-29 human colorectal adenocarcinoma. In both cases, three groups were compared in the experiments. The first group did not receive therapy, the second group received one 200 μg bevacizumab dose for a treatment period (protocol-based therapy), and the third group received 1.1 μg bevacizumab every day (quasi-continuous therapy). Tumor volume measurement was performed by digital caliper and small animal MRI. The mathematical relationship between MRI-measured tumor volume and mass was investigated to estimate accurate tumor volume using caliper-measured data. A two-dimensional mathematical model was applied for tumor volume evaluation, and tumor- and therapy-specific constants were calculated for the three different groups. The effectiveness of bevacizumab administration was examined by statistical analysis. Results In the case of C38 adenocarcinoma, protocol-based treatment did not result in significantly smaller tumor volume compared to the no treatment group; however, there was a significant difference between untreated mice and mice who received quasi-continuous therapy (p = 0.002). In the case of HT-29 adenocarcinoma, the daily treatment with one-twelfth total dose resulted in significantly smaller tumors than the protocol-based treatment (p = 0.038). When the tumor has a symmetrical, solid closed shape (typically without treatment), volume can be evaluated accurately from caliper-measured data with the applied two-dimensional mathematical model. Conclusion Our results provide a theoretical background for a much more effective bevacizumab treatment using optimized administration. PMID:26540189

Idiopathic Granulomatous Mastitis: Comparison of Wide Local Excision with or without Corticosteroid Therapy

PubMed Central

Akcan, Alper; Öz, A. Bahadir; Dogan, Serap; Akgün, Hülya; Akyüz, Muhammet; Ok, Engin; Gök, Mustafa; Talih, Tutkun

2014-01-01

Summary Background Idiopathic granulomatous mastitis (IGM) is an uncommon chronic inflammatory disease of the breast with uncertain optimal treatment regimen. In this study, our purpose was to report our clinical experience with 74 IGM patients who were treated wide local excision with or without steroid therapy. Patients and Method 74 cases diagnosed histologically as IGM were identified from surgical and pathological records between January 1995 and January 2012. Group 1 (surgery-only group) comprised 53 patients, and the 21 patients in group 2 were treated with corticosteroids prior to surgical treatment (steroid-and-surgery group). Results Follow-up data were complete for 67 (91.7%) of the 73 patients. Recurrence developed in 4 (7.5%) patients in the surgery-only group, while there was no recurrence in the steroid-and-surgery group; the difference was not statistically significant (p = 0.19). Conclusion Systemic steroid therapy with surgical resection is the recommended first-line treatment strategy for IGM. PMID:24944554

Allocation of Rehabilitation Services for Older Adults in the Ontario Home Care System.

PubMed

Armstrong, Joshua J; Sims-Gould, Joanie; Stolee, Paul

Background: Physiotherapy and occupational therapy services can play a critical role in maintaining or improving the physical functioning, quality of life, and overall independence of older home care clients. Despite their importance, however, there is limited understanding of the factors that influence how rehabilitation services are allocated to older home care clients. The aim of this pilot study was to develop a preliminary understanding of the factors that influence decisions to allocate rehabilitation therapy services to older clients in the Ontario home care system, as perceived by three stakeholder groups. Methods: Semi-structured interviews were conducted with 10 key informants from three stakeholder groups: case managers, service providers, and health system policymakers. Results: Drivers of the allocation of occupational therapy and physiotherapy for older adults included functional needs and postoperative care. Participants identified challenges in providing home care rehabilitation to older adults, including impaired cognition and limited capacity in the home care system. Conclusions: Considering the changing demands for home care services, knowledge of current practices across the home care system can inform efforts to optimize rehabilitation services for the growing number of older adults. Further research is needed to advance the understanding of, and optimize rehabilitation service allocation to, older frail clients with multiple morbidities. Developing novel decision-support mechanisms and standardized clinical care pathways for older client populations may be beneficial.

Exploratory Study of 4D Versus 3D Robust Optimization in Intensity-Modulated Proton Therapy for Lung Cancer

PubMed Central

Liu, Wei; Schild, Steven E.; Chang, Joe Y.; Liao, Zhongxing; Chang, Yu-Hui; Wen, Zhifei; Shen, Jiajian; Stoker, Joshua B.; Ding, Xiaoning; Hu, Yanle; Sahoo, Narayan; Herman, Michael G.; Vargas, Carlos; Keole, Sameer; Wong, William; Bues, Martin

2015-01-01

Background To compare the impact of uncertainties and interplay effect on 3D and 4D robustly optimized intensity-modulated proton therapy (IMPT) plans for lung cancer in an exploratory methodology study. Methods IMPT plans were created for 11 non-randomly selected non-small-cell lung cancer (NSCLC) cases: 3D robustly optimized plans on average CTs with internal gross tumor volume density overridden to irradiate internal target volume, and 4D robustly optimized plans on 4D CTs to irradiate clinical target volume (CTV). Regular fractionation (66 Gy[RBE] in 33 fractions) were considered. In 4D optimization, the CTV of individual phases received non-uniform doses to achieve a uniform cumulative dose. The root-mean-square-dose volume histograms (RVH) measured the sensitivity of the dose to uncertainties, and the areas under the RVH curve (AUCs) were used to evaluate plan robustness. Dose evaluation software modeled time-dependent spot delivery to incorporate interplay effect with randomized starting phases of each field per fraction. Dose-volume histogram indices comparing CTV coverage, homogeneity, and normal tissue sparing were evaluated using Wilcoxon signed-rank test. Results 4D robust optimization plans led to smaller AUC for CTV (14.26 vs. 18.61 (p=0.001), better CTV coverage (Gy[RBE]) [D95% CTV: 60.6 vs 55.2 (p=0.001)], and better CTV homogeneity [D5%–D95% CTV: 10.3 vs 17.7 (p=0.002)] in the face of uncertainties. With interplay effect considered, 4D robust optimization produced plans with better target coverage [D95% CTV: 64.5 vs 63.8 (p=0.0068)], comparable target homogeneity, and comparable normal tissue protection. The benefits from 4D robust optimization were most obvious for the 2 typical stage III lung cancer patients. Conclusions Our exploratory methodology study showed that, compared to 3D robust optimization, 4D robust optimization produced significantly more robust and interplay-effect-resistant plans for targets with comparable dose distributions for normal tissues. A further study with a larger and more realistic patient population is warranted to generalize the conclusions. PMID:26725727

Use of allopurinol with low-dose 6-mercaptopurine in inflammatory bowel disease to achieve optimal active metabolite levels: A review of four cases and the literature

PubMed Central

Witte, Todd N; Ginsberg, Allen L

2008-01-01

BACKGROUND: At least one-third of patients with inflammatory bowel disease do not respond or are intolerant to therapy with 6-mercaptopurine (6-MP). A subgroup fails to attain optimal levels of 6-thioguanine nucleotide (6-TGN) and instead shunts to 6-methylmercaptopurine nucleotide (6-MMPN). PATIENTS AND METHODS: A retrospective chart review was conducted, and four patients are described who had been previously unable to achieve optimal 6-TGN metabolite levels until allopurinol was added to their treatment. RESULTS: All four patients achieved optimal 6-TGN levels and undetectable 6-MMPN with a mean 6-MP dose of 0.49 mg/kg. Three achieved steroid-free clinical remission. Two of those three patients had normalization of liver enzymes; one patient had baseline normal liver enzymes despite an initial 6-MMPN level of 27,369 pmol/8×108 red blood cells. Two patients experienced reversible leukopenia. CONCLUSIONS: Combination allopurinol and low-dose 6-MP is an effective means to achieve optimal metabolite levels and steroid-free clinical remission in previously refractory patients. Caution is advised. PMID:18299738

Accuracy of Rhenium-188 SPECT/CT activity quantification for applications in radionuclide therapy using clinical reconstruction methods.

PubMed

Esquinas, Pedro L; Uribe, Carlos F; Gonzalez, M; Rodríguez-Rodríguez, Cristina; Häfeli, Urs O; Celler, Anna

2017-07-20

The main applications of 188 Re in radionuclide therapies include trans-arterial liver radioembolization and palliation of painful bone-metastases. In order to optimize 188 Re therapies, the accurate determination of radiation dose delivered to tumors and organs at risk is required. Single photon emission computed tomography (SPECT) can be used to perform such dosimetry calculations. However, the accuracy of dosimetry estimates strongly depends on the accuracy of activity quantification in 188 Re images. In this study, we performed a series of phantom experiments aiming to investigate the accuracy of activity quantification for 188 Re SPECT using high-energy and medium-energy collimators. Objects of different shapes and sizes were scanned in Air, non-radioactive water (Cold-water) and water with activity (Hot-water). The ordered subset expectation maximization algorithm with clinically available corrections (CT-based attenuation, triple-energy window (TEW) scatter and resolution recovery was used). For high activities, the dead-time corrections were applied. The accuracy of activity quantification was evaluated using the ratio of the reconstructed activity in each object to this object's true activity. Each object's activity was determined with three segmentation methods: a 1% fixed threshold (for cold background), a 40% fixed threshold and a CT-based segmentation. Additionally, the activity recovered in the entire phantom, as well as the average activity concentration of the phantom background were compared to their true values. Finally, Monte-Carlo simulations of a commercial [Formula: see text]-camera were performed to investigate the accuracy of the TEW method. Good quantification accuracy (errors  <10%) was achieved for the entire phantom, the hot-background activity concentration and for objects in cold background segmented with a 1% threshold. However, the accuracy of activity quantification for objects segmented with 40% threshold or CT-based methods decreased (errors  >15%), mostly due to partial-volume effects. The Monte-Carlo simulations confirmed that TEW-scatter correction applied to 188 Re, although practical, yields only approximate estimates of the true scatter.

Optimizing catecholaminergic polymorphic ventricular tachycardia therapy in calsequestrin-mutant mice

PubMed Central

Katz, Guy; Khoury, Assad; Kurtzwald, Efrat; Hochhauser, Edith; Porat, Eyal; Shainberg, Asher; Seidman, Jonathan G.; Seidman, Christine E.; Lorber, Abraham; Eldar, Michael; Arad, Michael

2014-01-01

BACKGROUND Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a lethal arrhythmia provoked by physical or emotional stress and mediated by spontaneous Ca2+ release and delayed after-depolarizations. Beta-adrenergic blockers are the therapy of choice but fail to control arrhythmia in up to 50% of patients. OBJECTIVE To optimize antiarrhythmic therapy in recessively inherited CPVT caused by calsequestrin (CASQ2) mutations. METHODS Murine heart rhythm telemetry was obtained at rest, during treadmill exercise, and after injection of epinephrine. The protocol was repeated after injection of different antiarrhythmic drugs. Results were then validated in human patients. RESULTS Adult CASQ2 mutant mice had complex ventricular arrhythmia at rest and developed bidirectional and polymorphic ventricular tachycardia on exertion. Class I antiarrhythmic agents (procainamide, lidocaine, flecainide) were ineffective in controlling arrhythmia. Propranolol and sotalol attenuated arrhythmia at rest but failed to prevent VT during sympathetic stimulation. The calcium channel blocker verapamil showed a dose-dependent protection against CPVT. Verapamil was more effective than the dihydropyridine L-type Ca2+ channel blocker nifedipine, and its activity was markedly enhanced when combined with propranolol. Human patients homozygous for CASQ2D307H mutation, remaining symptomatic despite chronic β-blocker therapy, underwent exercise testing according to the Bruce protocol with continuous electrocardiogram recording. Verapamil was combined with propranolol at maximum tolerated doses. Adding verapamil attenuated ventricular arrhythmia and prolonged exercise duration in five of 11 patients. CONCLUSION Verapamil is highly effective against catecholamine-induced arrhythmia in mice with CASQ2 mutations and may potentiate the antiarrhythmic activity of β-blockers in humans with CPVT2. PMID:20620233

What is the Optimal Strategy for Adaptive Servo-Ventilation Therapy?

PubMed

Imamura, Teruhiko; Kinugawa, Koichiro

2018-05-23

Clinical advantages in the adaptive servo-ventilation (ASV) therapy have been reported in selected heart failure patients with/without sleep-disorder breathing, whereas multicenter randomized control trials could not demonstrate such advantages. Considering this discrepancy, optimal patient selection and device setting may be a key for the successful ASV therapy. Hemodynamic and echocardiographic parameters indicating pulmonary congestion such as elevated pulmonary capillary wedge pressure were reported as predictors of good response to ASV therapy. Recently, parameters indicating right ventricular dysfunction also have been reported as good predictors. Optimal device setting with appropriate pressure setting during appropriate time may also be a key. Large-scale prospective trial with optimal patient selection and optimal device setting is warranted.

Coronary Intervention for Persistent Occlusion after Myocardial Infarction

PubMed Central

Hochman, Judith S.; Lamas, Gervasio A.; Buller, Christopher E.; Dzavik, Vladimir; Reynolds, Harmony R.; Abramsky, Staci J.; Forman, Sandra; Ruzyllo, Witold; Maggioni, Aldo P.; White, Harvey; Sadowski, Zygmunt; Carvalho, Antonio C.; Rankin, Jamie M.; Renkin, Jean P.; Steg, P. Gabriel; Mascette, Alice M.; Sopko, George; Pfisterer, Matthias E.; Leor, Jonathan; Fridrich, Viliam; Mark, Daniel B.; Knatterud, Genell L.

2007-01-01

BACKGROUND It is unclear whether stable, high-risk patients with persistent total occlusion of the infarct-related coronary artery identified after the currently accepted period for myocardial salvage has passed should undergo percutaneous coronary intervention (PCI) in addition to receiving optimal medical therapy to reduce the risk of subsequent events. METHODS We conducted a randomized study involving 2166 stable patients who had total occlusion of the infarct-related artery 3 to 28 days after myocardial infarction and who met a high-risk criterion (an ejection fraction of <50% or proximal occlusion). Of these patients, 1082 were assigned to routine PCI and stenting with optimal medical therapy, and 1084 were assigned to optimal medical therapy alone. The primary end point was a composite of death, myocardial reinfarction, or New York Heart Association (NYHA) class IV heart failure. RESULTS The 4-year cumulative primary event rate was 17.2% in the PCI group and 15.6% in the medical therapy group (hazard ratio for death, reinfarction, or heart failure in the PCI group as compared with the medical therapy group, 1.16; 95% confidence interval [CI], 0.92 to 1.45; P = 0.20). Rates of myocardial reinfarction (fatal and nonfatal) were 7.0% and 5.3% in the two groups, respectively (hazard ratio, 1.36; 95% CI, 0.92 to 2.00; P = 0.13). Rates of nonfatal reinfarction were 6.9% and 5.0%, respectively (hazard ratio, 1.44; 95% CI, 0.96 to 2.16; P = 0.08); only six reinfarctions (0.6%) were related to assigned PCI procedures. Rates of NYHA class IV heart failure (4.4% vs. 4.5%) and death (9.1% vs. 9.4%) were similar. There was no interaction between treatment effect and any subgroup variable (age, sex, race or ethnic group, infarct-related artery, ejection fraction, diabetes, Killip class, and the time from myocardial infarction to randomization). CONCLUSIONS PCI did not reduce the occurrence of death, reinfarction, or heart failure, and there was a trend toward excess reinfarction during 4 years of follow-up in stable patients with occlusion of the infarct-related artery 3 to 28 days after myocardial infarction. (ClinicalTrials.gov number, NCT00004562.) PMID:17105759

Adverse prognostic value of peritumoral vascular invasion: is it abrogated by adequate endocrine adjuvant therapy? Results from two International Breast Cancer Study Group randomized trials of chemoendocrine adjuvant therapy for early breast cancer

PubMed Central

Viale, G.; Giobbie-Hurder, A.; Gusterson, B. A.; Maiorano, E.; Mastropasqua, M. G.; Sonzogni, A.; Mallon, E.; Colleoni, M.; Castiglione-Gertsch, M.; Regan, M. M.; Brown, R. W.; Golouh, R.; Crivellari, D.; Karlsson, P.; Öhlschlegel, C.; Gelber, R. D.; Goldhirsch, A.; Coates, A. S.

2010-01-01

Background: Peritumoral vascular invasion (PVI) may assist in assigning optimal adjuvant systemic therapy for women with early breast cancer. Patients and methods: Patients participated in two International Breast Cancer Study Group randomized trials testing chemoendocrine adjuvant therapies in premenopausal (trial VIII) or postmenopausal (trial IX) node-negative breast cancer. PVI was assessed by institutional pathologists and/or central review on hematoxylin–eosin-stained slides in 99% of patients (analysis cohort 2754 patients, median follow-up >9 years). Results: PVI, present in 23% of the tumors, was associated with higher grade tumors and larger tumor size (trial IX only). Presence of PVI increased locoregional and distant recurrence and was significantly associated with poorer disease-free survival. The adverse prognostic impact of PVI in trial VIII was limited to premenopausal patients with endocrine-responsive tumors randomized to therapies not containing goserelin, and conversely the beneficial effect of goserelin was limited to patients whose tumors showed PVI. In trial IX, all patients received tamoxifen: the adverse prognostic impact of PVI was limited to patients with receptor-negative tumors regardless of chemotherapy. Conclusion: Adequate endocrine adjuvant therapy appears to abrogate the adverse impact of PVI in node-negative disease, while PVI may identify patients who will benefit particularly from adjuvant therapy. PMID:19633051

Observation of combined/optimized therapy of Lamivudine and Adefovir Dipivoxyl for hepatitis B-induced decompensated cirrhosis with baseline HBV DNA>1,000 IU/mL.

PubMed

Zhang, D; Zhao, G; Li, L; Li, Z

2017-01-01

This study aimed to observe and compare the efficacy and safety of the combined therapy and two different optimized therapies of lamivudine (LAM) and adefovir dipivoxil (ADV), as well as entecavir (ETV) monotherapy in patients with hepatitis B-induced decompensated cirrhosis. Method : A total of 127 patients with decompensated cirrhosis were divided into four groups, and each group received different doses of regimens: initial combination of LAM and ADV, ADV add-on therapies with previous 12-week LAM, ADV add-on therapies with previous 24-week LAM, and ETV monotherapy. At the end of the treatment, the level of alanine amino-transferase (ALT), albumin (ALB) and total bilirubin (TBIL) in the combination therapy group and 12-week optimized therapy group were significantly improved. For the 24-week optimized therapy group, only ALT levels revealed a significant improvement. There were no obvious differences in the normalization rate of ALT, negative conversion rate of HBV DNA and HBeAg, as well as improvement in Child-Pugh scores among the combination therapy group, 12-week optimized therapy group, and ETV monotherapy group. However, the difference among these three groups and the 24-week optimized therapy group were significant. Differences were not observed in the HBeAg seroconversion between each group. Differences in blood urea nitrogen, serum creatinine, creatine kinase, or other serious adverse effects were not observed in each group at the end of the 96-week treatment. Combination therapy and early ADV addition were the preferred approaches in the antiviral strategy for the treatment of hepatitis B-induced decompensated cirrhosis.

Therapy optimization in multiple sclerosis: a prospective observational study of therapy compliance and outcomes

PubMed Central

2014-01-01

Background Data sources for MS research are numerous but rarely provide an objective measure of drug therapy compliance coupled with patient-reported health outcomes. The objective of this paper is to describe the methods and baseline characteristics of the Therapy Optimization in MS (TOP MS) study designed to investigate the relationship between disease-modifying therapy compliance and health outcomes. Methods TOP MS was designed as a prospective, observational, nationwide patient-focused study using an internet portal for data entry. The protocol was reviewed and approved by Sterling IRB. The study was registered with ClinicalTrials.gov. It captured structured survey data monthly from MS patients recruited by specialty pharmacies. Data collection included the clinical characteristics of MS such as MS relapses. Disability, quality of life and work productivity and activity impairment were assessed quarterly with well-validated scales. When events like severe fatigue or new or worsening depression were reported, feedback was provided to treating physicians. The therapy compliance measure was derived from pharmacy drug shipment records uploaded to the study database. The data presented in this paper use descriptive statistics. Results The TOP MS Study enrolled 2966 participants receiving their disease-modifying therapy (DMT) from specialty pharmacies. The mean age of the sample was 49 years, 80.4% were female, 89.9% were Caucasian and 55.7% were employed full or part time. Mean time since first symptoms was 11.5 years; mean duration since diagnosis was 9.5 years. Patient-reported EDSS was 3.5; 72.2% had a relapsing-remitting disease course. The most commonly reported symptoms at the time of enrollment were fatigue (74.7%), impaired coordination or balance (61.8%) and numbness and tingling (61.2%). Half of the sample was using glatiramer acetate and half was using beta-interferons. Conclusion Demographic and clinical characteristics of the TOP MS sample at enrollment are consistent with other community-based MS samples, and the sample appears to be representative of DMT users in the US. TOP MS data can be used to explore the associations between disease-modifying therapy compliance and health outcomes. Trial registration ClinicalTrials.gov (NCT00819000) PMID:24624979

Antithrombotic Therapy for Atrial Fibrillation

PubMed Central

You, John J.; Singer, Daniel E.; Howard, Patricia A.; Lane, Deirdre A.; Eckman, Mark H.; Fang, Margaret C.; Hylek, Elaine M.; Schulman, Sam; Go, Alan S.; Hughes, Michael; Spencer, Frederick A.; Manning, Warren J.; Halperin, Jonathan L.

2012-01-01

Background: The risk of stroke varies considerably across different groups of patients with atrial fibrillation (AF). Antithrombotic prophylaxis for stroke is associated with an increased risk of bleeding. We provide recommendations for antithrombotic treatment based on net clinical benefit for patients with AF at varying levels of stroke risk and in a number of common clinical scenarios. Methods: We used the methods described in the Methodology for the Development of Antithrombotic Therapy and Prevention of Thrombosis Guidelines: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines article of this supplement. Results: For patients with nonrheumatic AF, including those with paroxysmal AF, who are (1) at low risk of stroke (eg, CHADS2 [congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus, prior stroke or transient ischemic attack] score of 0), we suggest no therapy rather than antithrombotic therapy, and for patients choosing antithrombotic therapy, we suggest aspirin rather than oral anticoagulation or combination therapy with aspirin and clopidogrel; (2) at intermediate risk of stroke (eg, CHADS2 score of 1), we recommend oral anticoagulation rather than no therapy, and we suggest oral anticoagulation rather than aspirin or combination therapy with aspirin and clopidogrel; and (3) at high risk of stroke (eg, CHADS2 score of ≥ 2), we recommend oral anticoagulation rather than no therapy, aspirin, or combination therapy with aspirin and clopidogrel. Where we recommend or suggest in favor of oral anticoagulation, we suggest dabigatran 150 mg bid rather than adjusted-dose vitamin K antagonist therapy. Conclusions: Oral anticoagulation is the optimal choice of antithrombotic therapy for patients with AF at high risk of stroke (CHADS2 score of ≥ 2). At lower levels of stroke risk, antithrombotic treatment decisions will require a more individualized approach. PMID:22315271

Noninvasive, automatic optimization strategy in cardiac resynchronization therapy.

PubMed

Reumann, Matthias; Osswald, Brigitte; Doessel, Olaf

2007-07-01

Optimization of cardiac resynchronization therapy (CRT) is still unsolved. It has been shown that optimal electrode position,atrioventricular (AV) and interventricular (VV) delays improve the success of CRT and reduce the number of non-responders. However, no automatic, noninvasive optimization strategy exists to date. Cardiac resynchronization therapy was simulated on the Visible Man and a patient data-set including fiber orientation and ventricular heterogeneity. A cellular automaton was used for fast computation of ventricular excitation. An AV block and a left bundle branch block were simulated with 100%, 80% and 60% interventricular conduction velocity. A right apical and 12 left ventricular lead positions were set. Sequential optimization and optimization with the downhill simplex algorithm (DSA) were carried out. The minimal error between isochrones of the physiologic excitation and the therapy was computed automatically and leads to an optimal lead position and timing. Up to 1512 simulations were carried out per pathology per patient. One simulation took 4 minutes on an Apple Macintosh 2 GHz PowerPC G5. For each electrode pair an optimal pacemaker delay was found. The DSA reduced the number of simulations by an order of magnitude and the AV-delay and VV - delay were determined with a much higher resolution. The findings are well comparable with clinical studies. The presented computer model of CRT automatically evaluates an optimal lead position and AV-delay and VV-delay, which can be used to noninvasively plan an optimal therapy for an individual patient. The application of the DSA reduces the simulation time so that the strategy is suitable for pre-operative planning in clinical routine. Future work will focus on clinical evaluation of the computer models and integration of patient data for individualized therapy planning and optimization.

Wound Care Centers: Critical Thinking and Treatment Strategies for Wounds

PubMed

de Leon, Jean; Bohn, Gregory A; DiDomenico, Lawrence; Fearmonti, Regina; Gottlieb, H David; Lincoln, Katherine; Shah, Jayesh B; Shaw, Mark; Taveau, Horatio S; Thibodeaux, Kerry; Thomas, John D; Treadwell, Terry A

2016-10-01

Many wound care centers (WCCs) provide a specialized level of care using various wound care therapies and are managed by quali ed healthcare professionals (QHPs) from di erent specialty backgrounds such as family medicine, podiatry, and plastic surgery. However, these QHPs are sometimes challenged by reimbursement issues, limited therapy and dressing options, reduced access to multidisciplinary team members, and cost-driven factors unique to WCCs. To help address these issues, a meeting was convened by an expert panel of WCC physicians to discuss best practices for treating complex patients in a WCC. This publication presents an overview of WCC chal- lenges, describes a holistic approach to treating WCC patients, and provides clinical guidance on the decision-mak- ing process for selecting optimal treatment plans for the WCC patient. Clinical cases of atypical, surgical and chronic wounds seen in a WCC are also presented.

An evaluation of recruitment methods utilized for a clinical trial with periodontal and diabetes enrollment criteria: the Diabetes and Periodontal Therapy Trial

PubMed Central

Schoenfeld, Elinor R; Hyman, Leslie; Simpson, Leslie Long; Michalowicz, Bryan; Reddy, Michael; Gelato, Marie; Hou, Wei; Engebretson, Steven P; Hytner, Catherine; Lenton, Pat

2014-01-01

Background Diabetes and its complications are a major United States public health concern. Methods The Diabetes and Periodontal Therapy Trial (DPTT) evaluated whether non-surgical treatment of periodontal disease influenced diabetes management among persons with Type 2 diabetes and periodontitis. The aim of this study was to evaluate DPTT’s many recruitment strategies in terms of enrollment success. Results/Conclusion Targeted recruitment strategies were more effective in identifying individuals who met periodontal and diabetes eligibility criteria. Individuals eligible for a baseline visit/enrollment were more often male, had a younger age at diabetes diagnosis, a longer diabetes duration, more often Hispanic and less often African–American. Tracking and evaluating recruitment sources during study enrollment optimized recruitment methods to enroll a diverse participant population based upon gender, race and ethnicity. PMID:25574373

Dispositional optimism as predictor of outcome in short- and long-term psychotherapy.

PubMed

Heinonen, Erkki; Heiskanen, Tiia; Lindfors, Olavi; Härkäpää, Kristiina; Knekt, Paul

2017-09-01

Dispositional optimism predicts various beneficial outcomes in somatic health and treatment, but has been little studied in psychotherapy. This study investigated whether an optimistic disposition differentially predicts patients' ability to benefit from short-term versus long-term psychotherapy. A total of 326 adult outpatients with mood and/or anxiety disorder were randomized into short-term (solution-focused or short-term psychodynamic) or long-term psychodynamic therapy and followed up for 3 years. Dispositional optimism was assessed by patients at baseline with the self-rated Life Orientation Test (LOT) questionnaire. Outcome was assessed at baseline and seven times during the follow-up, in terms of depressive (BDI, HDRS), anxiety (SCL-90-ANX, HARS), and general psychiatric symptoms (SCL-90-GSI), all seven follow-up points including patients' self-reports and three including interview-based measures. Lower dispositional optimism predicted faster symptom reduction in short-term than in long-term psychotherapy. Higher optimism predicted equally rapid and eventually greater benefits in long-term, as compared to short-term, psychotherapy. Weaker optimism appeared to predict sustenance of problems early in long-term therapy. Stronger optimism seems to best facilitate engaging in and benefiting from a long-term therapy process. Closer research might clarify the psychological processes responsible for these effects and help fine-tune both briefer and longer interventions to optimize treatment effectiveness for particular patients and their psychological qualities. Weaker dispositional optimism does not appear to inhibit brief therapy from effecting symptomatic recovery. Patients with weaker optimism do not seem to gain added benefits from long-term therapy, but instead may be susceptible to prolonged psychiatric symptoms in the early stages of long-term therapy. © 2016 The British Psychological Society.

Exogenous surfactant therapy in 2013: what is next? who, when and how should we treat newborn infants in the future?

PubMed Central

2013-01-01

Background Surfactant therapy is one of the few treatments that have dramatically changed clinical practice in neonatology. In addition to respiratory distress syndrome (RDS), surfactant deficiency is observed in many other clinical situations in term and preterm infants, raising several questions regarding the use of surfactant therapy. Objectives This review focuses on several points of interest, including some controversial or confusing topics being faced by clinicians together with emerging or innovative concepts and techniques, according to the state of the art and the published literature as of 2013. Surfactant therapy has primarily focused on RDS in the preterm newborn. However, whether this treatment would be of benefit to a more heterogeneous population of infants with lung diseases other than RDS needs to be determined. Early trials have highlighted the benefits of prophylactic surfactant administration to newborns judged to be at risk of developing RDS. In preterm newborns that have undergone prenatal lung maturation with steroids and early treatment with continuous positive airway pressure (CPAP), the criteria for surfactant administration, including the optimal time and the severity of RDS, are still under discussion. Tracheal intubation is no longer systematically done for surfactant administration to newborns. Alternative modes of surfactant administration, including minimally-invasive and aerosolized delivery, could thus allow this treatment to be used in cases of RDS in unstable preterm newborns, in whom the tracheal intubation procedure still poses an ethical and medical challenge. Conclusion The optimization of the uses and methods of surfactant administration will be one of the most important challenges in neonatal intensive care in the years to come. PMID:24112693

DOE Office of Scientific and Technical Information (OSTI.GOV)

Beltran, C; Kamal, H

Purpose: To provide a multicriteria optimization algorithm for intensity modulated radiation therapy using pencil proton beam scanning. Methods: Intensity modulated radiation therapy using pencil proton beam scanning requires efficient optimization algorithms to overcome the uncertainties in the Bragg peaks locations. This work is focused on optimization algorithms that are based on Monte Carlo simulation of the treatment planning and use the weights and the dose volume histogram (DVH) control points to steer toward desired plans. The proton beam treatment planning process based on single objective optimization (representing a weighted sum of multiple objectives) usually leads to time-consuming iterations involving treatmentmore » planning team members. We proved a time efficient multicriteria optimization algorithm that is developed to run on NVIDIA GPU (Graphical Processing Units) cluster. The multicriteria optimization algorithm running time benefits from up-sampling of the CT voxel size of the calculations without loss of fidelity. Results: We will present preliminary results of Multicriteria optimization for intensity modulated proton therapy based on DVH control points. The results will show optimization results of a phantom case and a brain tumor case. Conclusion: The multicriteria optimization of the intensity modulated radiation therapy using pencil proton beam scanning provides a novel tool for treatment planning. Work support by a grant from Varian Inc.« less

Rationale and Design of the Randomized Evaluation of an Ambulatory Care Pharmacist-Led Intervention to Optimize Urate Lowering Pathways (RAmP-UP) Study

PubMed Central

Coburn, Brian W; Cheetham, T Craig; Rashid, Nazia; Chang, John M; Levy, Gerald D; Kerimian, Artak; Low, Kimberly J; Redden, David T; Bridges, S Louis; Saag, Kenneth G; Curtis, Jeffrey R; Mikuls, Ted R

2016-01-01

Background Despite the availability of effective therapies, most gout patients achieve suboptimal treatment outcomes. Current best practices suggest gradual dose-escalation of urate lowering therapy and serial serum urate (sUA) measurement to achieve sUA < 6.0 mg/dl. However, this strategy is not routinely used. Here we present the study design rationale and development for a pharmacist-led intervention to promote sUA goal attainment. Methods To overcome barriers in achieving optimal outcomes, we planned and implemented the Randomized Evaluation of an Ambulatory Care Pharmacist-Led Intervention to Optimize Urate Lowering Pathways (RAmP-UP) study. This is a large pragmatic cluster-randomized trial designed to assess a highly automated, pharmacist-led intervention to optimize allopurinol treatment in gout. Ambulatory clinics (n=101) from a large health system were randomized to deliver either the pharmacist-led intervention or usual care to gout patients over the age of 18 years newly initiating allopurinol. All participants received educational materials and could opt-out of the study. For intervention sites, pharmacists conducted outreach primarily via an automated telephone interactive voice recognition system. The outreach, guided by a gout care algorithm developed for this study, systematically promoted adherence assessment, facilitated sUA testing, provided education, and adjusted allopurinol dosing. The primary study outcomes are achievement of sUA < 6.0 mg/dl and treatment adherence determined after one year. With follow-up ongoing, study results will be reported subsequently. Conclusion Ambulatory care pharmacists and automated calling technology represent potentially important, underutilized resources for improving health outcomes for gout patients. PMID:27449546

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

NASA Astrophysics Data System (ADS)

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 can help improve dose conformity, homogeneity, and organ sparing simultaneously using the same beam trajectory length and delivery time as a coplanar VMAT plan.

EUD-based biological optimization for carbon ion therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brüningk, Sarah C., E-mail: sarah.brueningk@icr.ac.uk; Kamp, Florian; Wilkens, Jan J.

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 equivalentmore » 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 therapy, the optimization by biological objective functions resulted in slightly superior treatment plans in terms of final EUD for the organs at risk (OARs) compared to voxel-based optimization approaches. This observation was made independent of the underlying objective function metric. An absolute gain in OAR sparing was observed for quadratic objective functions, whereas intersecting DVHs were found for logistic approaches. Even for considerable under- or overestimations of the used effect- or dose–volume parameters during the optimization, treatment plans were obtained that were of similar quality as the results of a voxel-based optimization. Conclusions: EUD-based optimization with either of the presented concepts can successfully be applied to treatment plan optimization. This makes EUE-based optimization for carbon ion therapy a useful tool to optimize more specifically in the sense of biological outcome while voxel-to-voxel variations of the biological effectiveness are still properly accounted for. This may be advantageous in terms of computational cost during treatment plan optimization but also enables a straight forward comparison of different fractionation schemes or treatment modalities.« less

Development and optimization of a diode laser for photodynamic therapy

PubMed Central

Lim, Hyun Soo

2011-01-01

Background and Aims: This study demonstrated the development of a laser system for cancer treatment with photodynamic therapy (PDT) based on a 635 nm laser diode. In order to optimize efficacy in PDT, the ideal laser system should deliver a homogeneous nondivergent light energy with a variable spot size and specific wavelength at a stable output power. Materials and Methods: We developed a digital laser beam controller using the constant current method to protect the laser diode resonator from the current spikes and other fluctuations, and electrical faults. To improve the PDT effects, the laser system should deliver stable laser energy in continuous wave (CW), burst mode and super burst mode, with variable irradiation times depending on the tumor type and condition. Results and Comments: The experimental results showed the diode laser system described herein was eminently suitable for PDT. The laser beam was homogeneous without diverging and the output power increased stably and in a linear manner from 10 mW to 1500 mW according to the increasing input current. Variation between the set and delivered output was less than 7%. Conclusions: The diode laser system developed by the author for use in PDT was compact, user-friendly, and delivered a stable and easily adjustable output power at a specific wavelength and user-set emission modes. PMID:24155529

Optimization of pressure settings during adaptive servo-ventilation support using real-time heart rate variability assessment: initial case report.

PubMed

Imamura, Teruhiko; Nitta, Daisuke; Kinugawa, Koichiro

2017-01-05

Adaptive servo-ventilation (ASV) therapy is a recent non-invasive positive pressure ventilation therapy that was developed for patients with heart failure (HF) refractory to optimal medical therapy. However, it is likely that ASV therapy at relatively higher pressure setting worsens some of the patients' prognosis compared with optimal medical therapy. Therefore, identification of optimal pressure settings of ASV therapy is warranted. We present the case of a 42-year-old male with HF, which was caused by dilated cardiomyopathy, who was admitted to our institution for evaluating his eligibility for heart transplantation. To identify the optimal pressure setting [peak end-expiratory pressure (PEEP) ramp test], we performed an ASV support test, during which the PEEP settings were set at levels ranging from 4 to 8 mmHg, and a heart rate variability (HRV) analysis using the MemCalc power spectral density method. Clinical parameters varied dramatically during the PEEP ramp test. Over incremental PEEP levels, pulmonary capillary wedge pressure, cardiac index and high-frequency level (reflecting parasympathetic activity) decreased; however, the low-frequency level increased along with increase in plasma noradrenaline concentrations. An inappropriately high PEEP setting may stimulate sympathetic nerve activity accompanied by decreased cardiac output. This was the first report on the PEEP ramp test during ASV therapy. Further research is warranted to determine whether use of optimal pressure settings using HRV analyses may improve the long-term prognosis of such patients.

Open-loop-feedback control of serum drug concentrations: pharmacokinetic approaches to drug therapy.

PubMed

Jelliffe, R W

1983-01-01

Recent developments to optimize open-loop-feedback control of drug dosage regimens, generally applicable to pharmacokinetically oriented therapy with many drugs, involve computation of patient-individualized strategies for obtaining desired serum drug concentrations. Analyses of past therapy are performed by least squares, extended least squares, and maximum a posteriori probability Bayesian methods of fitting pharmacokinetic models to serum level data. Future possibilities for truly optimal open-loop-feedback therapy with full Bayesian methods, and conceivably for optimal closed-loop therapy in such data-poor clinical situations, are also discussed. Implementation of these various therapeutic strategies, using automated, locally controlled infusion devices, has also been achieved in prototype form.

Improvement of LOD in Fluorescence Detection with Spectrally Nonuniform Background by Optimization of Emission Filtering.

PubMed

Galievsky, Victor A; Stasheuski, Alexander S; Krylov, Sergey N

2017-10-17

The limit-of-detection (LOD) in analytical instruments with fluorescence detection can be improved by reducing noise of optical background. Efficiently reducing optical background noise in systems with spectrally nonuniform background requires complex optimization of an emission filter-the main element of spectral filtration. Here, we introduce a filter-optimization method, which utilizes an expression for the signal-to-noise ratio (SNR) as a function of (i) all noise components (dark, shot, and flicker), (ii) emission spectrum of the analyte, (iii) emission spectrum of the optical background, and (iv) transmittance spectrum of the emission filter. In essence, the noise components and the emission spectra are determined experimentally and substituted into the expression. This leaves a single variable-the transmittance spectrum of the filter-which is optimized numerically by maximizing SNR. Maximizing SNR provides an accurate way of filter optimization, while a previously used approach based on maximizing a signal-to-background ratio (SBR) is the approximation that can lead to much poorer LOD specifically in detection of fluorescently labeled biomolecules. The proposed filter-optimization method will be an indispensable tool for developing new and improving existing fluorescence-detection systems aiming at ultimately low LOD.

Approaches to enhancing the quality of drug therapy. A joint statement by the CMA and the Canadian Pharmaceutical Association. Canadian Medical Association.

PubMed Central

1996-01-01

This joint statement was developed by the CMA and the Canadian Pharmaceutical Association, a national association of pharmacists, and includes the goal of drug therapy, strategies for collaboration to optimize drug therapy and physicians' and pharmacists' responsibilities in drug therapy. The statement recognizes the importance of patients, physicians and pharmacists working in close collaboration and partnership to achieve optimal outcomes from drug therapy. PMID:8823225

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

PubMed

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.

Impact of the HIV-1 genetic background and HIV-1 population size on the evolution of raltegravir resistance.

PubMed

Fun, Axel; Leitner, Thomas; Vandekerckhove, Linos; Däumer, Martin; Thielen, Alexander; Buchholz, Bernd; Hoepelman, Andy I M; Gisolf, Elizabeth H; Schipper, Pauline J; Wensing, Annemarie M J; Nijhuis, Monique

2018-01-05

Emergence of resistance against integrase inhibitor raltegravir in human immunodeficiency virus type 1 (HIV-1) patients is generally associated with selection of one of three signature mutations: Y143C/R, Q148K/H/R or N155H, representing three distinct resistance pathways. The mechanisms that drive selection of a specific pathway are still poorly understood. We investigated the impact of the HIV-1 genetic background and population dynamics on the emergence of raltegravir resistance. Using deep sequencing we analyzed the integrase coding sequence (CDS) in longitudinal samples from five patients who initiated raltegravir plus optimized background therapy at viral loads > 5000 copies/ml. To investigate the role of the HIV-1 genetic background we created recombinant viruses containing the viral integrase coding region from pre-raltegravir samples from two patients in whom raltegravir resistance developed through different pathways. The in vitro selections performed with these recombinant viruses were designed to mimic natural population bottlenecks. Deep sequencing analysis of the viral integrase CDS revealed that the virological response to raltegravir containing therapy inversely correlated with the relative amount of unique sequence variants that emerged suggesting diversifying selection during drug pressure. In 4/5 patients multiple signature mutations representing different resistance pathways were observed. Interestingly, the resistant population can consist of a single resistant variant that completely dominates the population but also of multiple variants from different resistance pathways that coexist in the viral population. We also found evidence for increased diversification after stronger bottlenecks. In vitro selections with low viral titers, mimicking population bottlenecks, revealed that both recombinant viruses and HXB2 reference virus were able to select mutations from different resistance pathways, although typically only one resistance pathway emerged in each individual culture. The generation of a specific raltegravir resistant variant is not predisposed in the genetic background of the viral integrase CDS. Typically, in the early phases of therapy failure the sequence space is explored and multiple resistance pathways emerge and then compete for dominance which frequently results in a switch of the dominant population over time towards the fittest variant or even multiple variants of similar fitness that can coexist in the viral population.

Incorporating geometric ray tracing to generate initial conditions for intensity modulated arc therapy optimization

DOE Office of Scientific and Technical Information (OSTI.GOV)

Oliver, Mike; Gladwish, Adam; Craig, Jeff

2008-07-15

Purpose and background: Intensity modulated arc therapy (IMAT) is a rotational variant of Intensity modulated radiation therapy (IMRT) that is achieved by allowing the multileaf collimator (MLC) positions to vary as the gantry rotates around the patient. This work describes a method to generate an IMAT plan through the use of a fast ray tracing technique based on dosimetric and geometric information for setting initial MLC leaf positions prior to final IMAT optimization. Methods and materials: Three steps were used to generate an IMAT plan. The first step was to generate arcs based on anatomical contours. The second step wasmore » to generate ray importance factor (RIF) maps by ray tracing the dose distribution inside the planning target volume (PTV) to modify the MLC leaf positions of the anatomical arcs to reduce the maximum dose inside the PTV. The RIF maps were also segmented to create a new set of arcs to improve the dose to low dose voxels within the PTV. In the third step, the MLC leaf positions from all arcs were put through a leaf position optimization (LPO) algorithm and brought into a fast Monte Carlo dose calculation engine for a final dose calculation. The method was applied to two phantom cases, a clinical prostate case and the Radiological Physics Center (RPC)'s head and neck phantom. The authors assessed the plan improvements achieved by each step and compared plans with and without using RIF. They also compared the IMAT plan with an IMRT plan for the RPC phantom. Results: All plans that incorporated RIF and LPO had lower objective function values than those that incorporated LPO only. The objective function value was reduced by about 15% after the generation of RIF arcs and 52% after generation of RIF arcs and leaf position optimization. The IMAT plan for the RPC phantom had similar dose coverage for PTV1 and PTV2 (the same dose volume histogram curves), however, slightly lower dose to the normal tissues compared to a six-field IMRT plan. Conclusion: The use of a ray importance factor can generate initial IMAT arcs efficiently for further MLC leaf position optimization to obtain more favorable IMAT plan.« less

Anaplerotic Treatment of Long-Chain Fat Oxidation Disorders with Triheptanoin: Review of 15 years Experience

PubMed Central

Roe, Charles R.; Brunengraber, Henri

2015-01-01

Background The treatment of long-chain mitochondrial β-oxidation disorders (LC-FOD) with a low fat-high carbohydrate diet, a diet rich in medium-even-chain triglycerides (MCT), or a combination of both has been associated with high morbidity and mortality for decades. The pathological tableau appears to be caused by energy deficiency resulting from reduced availability of citric acid cycle (CAC) intermediates required for optimal oxidation of acetyl-CoA. This hypothesis was investigated by diet therapy with carnitine and anaplerotic triheptanoin (TH). Methods Fifty-two documented LC-FOD patients were studied in this investigation (age range: birth to 51 years). Safety monitoring included serial quantitative measurements of routine blood chemistries, blood levels of carnitine and acylcarnitines, and urinary organic acids. Results The average frequency of serious clinical complications were reduced from ~ 60 % with conventional diet therapy to 10 % with TH and carnitine treatment and mortality decreased from ~ 65 % with conventional diet therapy to 3.8 %. Carnitine supplementation was uncomplicated. Conclusion The energy deficiency in LC-FOD patients was corrected safely and more effectively with the triheptanoin diet and carnitine supplement than with conventional diet therapy. Safe intervention in neonates and infants will permit earlier intervention following pre-natal diagnosis or diagnosis by expanded newborn screening. PMID:26547562

[Changes of twenty-four-hour profile blood pressure and its correction of patients with arterial hypertension on the background of combined antihypertensive therapy application].

PubMed

Solomennchuk, T M; Slaba, N A; Prots'ko, V V; Bedzaĭ, A O

2014-01-01

The aim of this research was the study of efficiency and endurance antihypertensive therapy on the basis of fixed combination of enalapril and hydrochlorothiazide (HCTZ) and enalapril and HCTZ in combination with amlodipine according to the twenty-four-hour (? day-and-night) monitoring of blood pressure (? 24H BPM) of patients with arterial hypertension (AH) 2-3 severity. The study included 33 patients with 2-3 grade of hypertension (average age--54,40 ± 3.45 years). All patients performed ? 24H BPM before treatment and after 12 weeks of therapy. The combination of enalapril and HCTZ allowed to achieve target levels of blood pressure in 79% of patients, amlodipine additional purpose--in 86% of patients. We found that this therapy has a corrective effect on daily blood pressure profile, significantly reducing the load pressure and blood pressure variability. During treatment with the combination of enalapril and HCTZ combination of enalapril, HCTZ with amlodipine optimal daily profile of blood pressure after 12 weeks of reaching respectively 63.1% and 71.4% of patients. The treatment with combination of enalapril and HCTZ and adding of amlodipine is characterized by good endurance and high adherence to treatment.

Managing diverse occupational therapy resources in a creative, corporate model.

PubMed

Baptiste, S

1993-10-01

Two occupational therapy departments were amalgamated into a corporate whole and charged with the development of a workable, corporate structure. The departmental model which was developed served to enhance the concepts of quality of working life, employee autonomy, management team and quality circle theory. This paper provides a background from business and organizational literature, and outlines the development of the departmental model, in concert with the adoption of the client-centred model of occupational performance as a department basis for practice. This development was taking place concurrently with larger, institutional changes into a decentralized clinical programme management model. Discussion highlights the level of staff satisfaction with the changes, areas of concern during the development of the system and plans for the future growth. During this period of massive and critical change in the delivery of health care services, there has been a trend in restructuring health care institutions towards decentralized models. This paper will describe the experience of one occupational therapy department in developing an innovative departmental structure involving participatory management amalgamation. It is believed that the experience of the past occupational therapy work units with one viable option for a renewed management model. Staff skill sets can be maximized and optimal potential realized while faced with inevitable resource shrinkage and service reorganization.

The use of lipid-lowering therapy for secondary prevention in patients undergoing percutaneous coronary intervention

PubMed Central

Ma, Jessica M; Jackevicius, Cynthia A; Genus, Uchenwa; Dzavik, Vladimir

2006-01-01

BACKGROUND Recent literature suggests that lipid-lowering therapy may have an early beneficial effect among patients undergoing percutaneous coronary intervention (PCI) because the therapy decreases cardiac mortality, morbidity and possibly restenosis. OBJECTIVE The primary objective of the present study was to determine the proportion of PCI patients receiving lipid-lowering therapy at a large, tertiary-care referral centre. METHODS Patients undergoing a first PCI between August 2000 and August 2002 with corresponding inpatient medication information were included in the study. Patient demographics, procedural variables, and lipid-lowering and other evidence-based cardiac medication data were collected. A multiple logistical regression model was constructed to evaluate the factors associated with the use of lipid-lowering therapy. RESULTS Of the 3254 cases included in the analyses, 52% were elective, 44% were urgent or salvage, and 4% were emergent. The mean patient age was 63 years, and 73% of patients were male. Over 76% of patients were receiving lipid-lowering therapy at the time of PCI. Patient use of other medications was as follows: acetylsalicylic acid in 96%, beta-blocker in 80% and angiotensin-converting enzyme inhibitor in 59%. In the multiple regression analysis, variables significantly associated with lipid-lowering therapy use included hypercholesterolemia, beta-blocker use, angiotensin-converting enzyme inhibitor use, case urgency, prior coronary artery bypass graft surgery, age and sex. CONCLUSION Lipid-lowering therapy use rates exceeded those previously reported in the literature. Women and patients undergoing elective procedures appear to be treated less often with lipid-lowering therapy. There remains an opportunity to further optimize use in this high-risk cohort at time of PCI. PMID:16639478

Advanced typical and atypical carcinoid tumours of the lung: management recommendations

PubMed Central

Melosky, B.

2018-01-01

Background Neuroendocrine tumours (nets) are classified by site of origin, with lung being the second most common primary site after the gastrointestinal tract. Lung nets are rare and heterogeneous, with varied pathologic and clinical features. Typical and atypical carcinoid tumours are low-grade lung nets which, compared with the more common high-grade nets, are associated with a more favourable prognosis. Still, optimal treatment strategies are lacking. Methods This review concentrates on classification and treatment strategies for metastatic low-grade lung nets, considering both typical and atypical carcinoids. The terminology can be confusing, and an attempt is made to simplify it. Promising results from recent trials that included lung nets are presented and discussed. Finally, guidelines from Europe and North America are discussed, and differences are noted. Results Even within the group of patients with low-grade nets, the presentation, the locations of metastasis, and the speed of progression can be very different. The initial work-up and an understanding of the tumour’s biology are key in making management decisions. Various treatment options—including somatostatin analogs, peptide receptor radioligand therapy, and biologic systemic therapy, specifically with the mtor (mechanistic target of rapamycin) inhibitor everolimus—are now available and are presented in a treatment algorithm. Summary Although lung nets are rare and evidence supporting optimal treatment strategies is lacking, the recent publication of trials that have included patients with lung nets advances evidence-based therapy for these tumours. Many variables have to be considered in managing these tumours that have received little attention. Education for treating physicians is needed.

Guideline-Concordant Cancer Care and Survival Among American Indian/Alaskan Native Patients

PubMed Central

Javid, Sara H.; Varghese, Thomas K.; Morris, Arden M.; Porter, Michael P.; He, Hao; Buchwald, Dedra; Flum, David R.

2014-01-01

BACKGROUND American Indians/Alaskan Natives (AI/ANs) have the worst 5-year cancer survival of all racial/ethnic groups in the United States. Causes for this disparity are unknown. The authors of this report examined the receipt of cancer treatment among AI/AN patients compared with white patients. METHODS This was a retrospective cohort study of 338,204 patients who were diagnosed at age ≥65 years with breast, colon, lung, or prostate cancer between 1996 and 2005 in the Surveillance, Epidemiology, and End Results-Medicare database. Nationally accepted guidelines for surgical and adjuvant therapy and surveillance were selected as metrics of optimal, guideline-concordant care. Treatment analyses compared AI/ANs with matched whites. RESULTS Across cancer types, AI/ANs were less likely to receive optimal cancer treatment and were less likely to undergo surgery (P ≤ .025 for all cancers). Adjuvant therapy rates were significantly lower for AI/AN patients with breast cancer (P <.001) and colon cancer (P = .001). Rates of post-treatment surveillance also were lower among AI/ANs and were statistically significantly lower for AI/AN patients with breast cancer (P = .002) and prostate cancer (P <.001). Nonreceipt of optimal cancer treatment was associated with significantly worse survival across cancer types. Disease-specific survival for those who did not undergo surgery was significantly lower for patients with breast cancer (hazard ratio [HR], 0.62), colon cancer (HR, 0.74), prostate cancer (HR, 0.52), and lung cancer (HR, 0.36). Survival rates also were significantly lower for those patients who did not receive adjuvant therapy for breast cancer (HR, 0.56), colon cancer (HR, 0.59), or prostate cancer (HR, 0.81; all 95% confidence intervals were <1.0). CONCLUSIONS Fewer AI/AN patients than white patients received guideline-concordant cancer treatment across the 4 most common cancers. Efforts to explain these differences are critical to improving cancer care and survival for AI/AN patients. PMID:24711210

Predictors of Long-Term Mortality and Frequent Re-Hospitalization in Patients with Acute Decompensated Heart Failure and Kidney Dysfunction Treated with Renin-Angiotensin System Blockers.

PubMed

Baydemir, Canan; Ural, Dilek; Karaüzüm, Kurtuluş; Balci, Sibel; Argan, Onur; Karaüzüm, Irem; Kozdağ, Güliz; Ağır, Ayşen A

2017-07-10

BACKGROUND Assessment of risk for all-cause mortality and re-hospitalization is an important task during discharge of acute heart failure (AHF) patients, as they warrant different management strategies. Treatment with optimal medical therapy may change predictors for these 2 end-points in AHF patients with renal dysfunction. The aim of this study was to evaluate the predictors for long-term outcome in AHF patients with kidney dysfunction who were discharged on optimal medical therapy. MATERIAL AND METHODS The study was conducted retrospectively. The study group consisted of 225 AHF patients with moderate-to-severe kidney dysfunction, who were hospitalized at Kocaeli University Hospital Cardiology Clinic and who were prescribed beta-blockers and ACE-inhibitors or angiotensin II receptor blockers at discharge. Clinical, echocardiographic, and biochemical predictors of the composite of total mortality and frequent re-hospitalization (≥3 hospitalizations during the follow-up) were assessed using Cox regression and the predictors for each end-point were assessed by competing risk regression analysis. RESULTS Incidence of all-cause mortality was 45.3% and frequent readmissions were 49.8% in a median follow-up of 54 months. The associates of the composite end-point were age, NYHA class, respiration rate on admission, eGFR, hypoalbuminemia, mitral valve E/E' ratio, and ejection fraction. In competing risk regression analysis, right-sided HF, hypoalbuminemia, age, and uric acid appeared as independent associates of all-cause mortality, whereas NYHA class, NT-proBNP, mitral valve E/E' ratio, and uric acid were predictors for re-hospitalization. CONCLUSIONS Predictors for all-cause mortality in AHF with kidney dysfunction treated with optimal therapy are mainly related to advanced HF with right-sided dysfunction, whereas frequent re-hospitalization is associated with volume overload manifested by increased mitral E/E' ratio and NT-proBNP levels.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Frank, Steven J., E-mail: sjfrank@mdanderson.org; Cox, James D.; Gillin, Michael

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 effectmore » 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.« less

Adaptive non-linear control for cancer therapy through a Fokker-Planck observer.

PubMed

Shakeri, Ehsan; Latif-Shabgahi, Gholamreza; Esmaeili Abharian, Amir

2018-04-01

In recent years, many efforts have been made to present optimal strategies for cancer therapy through the mathematical modelling of tumour-cell population dynamics and optimal control theory. In many cases, therapy effect is included in the drift term of the stochastic Gompertz model. By fitting the model with empirical data, the parameters of therapy function are estimated. The reported research works have not presented any algorithm to determine the optimal parameters of therapy function. In this study, a logarithmic therapy function is entered in the drift term of the Gompertz model. Using the proposed control algorithm, the therapy function parameters are predicted and adaptively adjusted. To control the growth of tumour-cell population, its moments must be manipulated. This study employs the probability density function (PDF) control approach because of its ability to control all the process moments. A Fokker-Planck-based non-linear stochastic observer will be used to determine the PDF of the process. A cost function based on the difference between a predefined desired PDF and PDF of tumour-cell population is defined. Using the proposed algorithm, the therapy function parameters are adjusted in such a manner that the cost function is minimised. The existence of an optimal therapy function is also proved. The numerical results are finally given to demonstrate the effectiveness of the proposed method.

Optimal use of novel agents in chronic lymphocytic leukemia.

PubMed

Smith, Mitchell R; Weiss, Robert F

2018-05-07

Novel agents are changing therapy for patients with CLL, but their optimal use remains unclear. We model the clinical situation in which CLL responds to therapy, but resistant clones, generally carrying del17p, progress and lead to relapse. Sub-clones of varying growth rates and treatment sensitivity affect predicted therapy outcomes. We explore effects of different approaches to starting novel agent in relation to bendamustine-rituximab induction therapy: at initiation of therapy, at the end of chemo-immunotherapy, at molecular relapse, or at clinical detection of relapse. The outcomes differ depending on the underlying clonal architecture, raising the concept that personalized approaches based on clinical evaluation of each patient's clonal architecture might optimize outcomes while minimizing toxicity and cost. Copyright © 2018 Elsevier Ltd. All rights reserved.

Real-Time Dosimetry and Optimization of Prostate Photodynamic Therapy

DTIC Science & Technology

2006-09-01

photodynamic therapy in patients with prostate cancer,” IPA 9th World Congress of Photodynamic Medicine, (2003). 2. Zhu TC, Diana S, Dimofte A...photodynamic therapy,” IPA 9th World Congress of Photodynamic Medicine, (2003). 3. Zhu TC, Altschuler M, Xiao Y, Finlay J, Dimofte A, Hahn SM, “Light...Optimization of treatment plan using Cimmino algorithm in prostate photodynamic therapy,” IPA 10th World Congress of Photodynamic Medicine, Munich

I-SWOT as instrument to individually optimize therapy of thoracoabdominal aortic aneurysms: Effective, norm-compliant and meeting the needs.

PubMed

Sachweh, A; von Kodolitsch, Y; Kölbel, T; Larena-Avellaneda, A; Wipper, S; Bernhardt, A M; Girdauskas, E; Detter, C; Reichenspurner, H; Blankart, C R; Debus, E S

2017-01-01

Guidelines summarize medical evidence, they identify the most efficient therapy under study conditions and recommend this therapy for use. The physician now has the challenge to translate a therapy that is efficient under laboratory conditions to a patient who is an individual person. To accomplish this task the physician has to make sure that (I) the ideal typical therapy is applicable and effective in this individual patient taking the special features into consideration, that (II) therapy is compliant with the norm including guidelines, laws and ethical requirements (conformity) and that (III) the therapy meets the patient's needs. How can physicians together with the patients translate the medical evidence into an individually optimized therapy? At the German Aortic Center in Hamburg we use I‑SWOT as an instrument to identify such individually optimized therapy. With I‑SWOT, we present an instrument with which we have developed an (I) efficient, (II) conform and (III) needs-oriented therapeutic strategy for individual patients. I-SWOT cross-tabulates strengths (S) and weaknesses (W) related to therapy with opportunities (O) and threats (T) related to individual patients. This I‑SWOT matrix identifies four fundamental types of strategy, which comprise "SO" maximizing strengths and opportunities, "WT" minimizing weaknesses and threats, "WO" minimizing weaknesses and maximizing opportunities and "ST" maximizing strengths and minimizing threats. We discuss the case of a patient with asymptomatic thoracoabdominal aneurysm to show how I‑SWOT is used to identify an individually optimized therapy strategy.

Long range personalized cancer treatment strategies incorporating evolutionary dynamics.

PubMed

Yeang, Chen-Hsiang; Beckman, Robert A

2016-10-22

Current cancer precision medicine strategies match therapies to static consensus molecular properties of an individual's cancer, thus determining the next therapeutic maneuver. These strategies typically maintain a constant treatment while the cancer is not worsening. However, cancers feature complicated sub-clonal structure and dynamic evolution. We have recently shown, in a comprehensive simulation of two non-cross resistant therapies across a broad parameter space representing realistic tumors, that substantial improvement in cure rates and median survival can be obtained utilizing dynamic precision medicine strategies. These dynamic strategies explicitly consider intratumoral heterogeneity and evolutionary dynamics, including predicted future drug resistance states, and reevaluate optimal therapy every 45 days. However, the optimization is performed in single 45 day steps ("single-step optimization"). Herein we evaluate analogous strategies that think multiple therapeutic maneuvers ahead, considering potential outcomes at 5 steps ahead ("multi-step optimization") or 40 steps ahead ("adaptive long term optimization (ALTO)") when recommending the optimal therapy in each 45 day block, in simulations involving both 2 and 3 non-cross resistant therapies. We also evaluate an ALTO approach for situations where simultaneous combination therapy is not feasible ("Adaptive long term optimization: serial monotherapy only (ALTO-SMO)"). Simulations utilize populations of 764,000 and 1,700,000 virtual patients for 2 and 3 drug cases, respectively. Each virtual patient represents a unique clinical presentation including sizes of major and minor tumor subclones, growth rates, evolution rates, and drug sensitivities. While multi-step optimization and ALTO provide no significant average survival benefit, cure rates are significantly increased by ALTO. Furthermore, in the subset of individual virtual patients demonstrating clinically significant difference in outcome between approaches, by far the majority show an advantage of multi-step or ALTO over single-step optimization. ALTO-SMO delivers cure rates superior or equal to those of single- or multi-step optimization, in 2 and 3 drug cases respectively. In selected virtual patients incurable by dynamic precision medicine using single-step optimization, analogous strategies that "think ahead" can deliver long-term survival and cure without any disadvantage for non-responders. When therapies require dose reduction in combination (due to toxicity), optimal strategies feature complex patterns involving rapidly interleaved pulses of combinations and high dose monotherapy. This article was reviewed by Wendy Cornell, Marek Kimmel, and Andrzej Swierniak. Wendy Cornell and Andrzej Swierniak are external reviewers (not members of the Biology Direct editorial board). Andrzej Swierniak was nominated by Marek Kimmel.

The clinical benefit of cardiac resynchronization therapy optimization using a device-based hemodynamic sensor in a patient with dilated cardiomyopathy: a case report.

PubMed

Volpicelli, Mario; Covino, Gregorio; Capogrosso, Paolo

2015-12-19

Results on the evolution of the clinical status of patients undergoing cardiac resynchronization therapy with a defibrillator after automatic optimization of their cardiac resynchronization therapy are scarce. We observed a rapid and important change in the clinical status of our non-responding patient following activation of a sensor capable of weekly atrioventricular and interventricular delays' optimization. A 78-year-old Caucasian man presented with dilated cardiomyopathy, left bundle branch block, a left ventricular ejection fraction of 35 %, New York Heart Association class III/IV heart failure, and paroxysmal atrial fibrillation. Our patient was implanted with a cardiac resynchronization device with a defibrillator and the SonRtip atrial lead. Right ventricular and left ventricular leads were also implanted. Because of the recurrence of atrial fibrillation, the automatic optimization was set off at discharge. Consequently, the device did not optimize atrioventricular and interventricular delays (programming at discharge: 125 ms for the atrioventricular delay and 0 ms for the interventriculardelay). Our patient was treated with an anti-arrhythmic drug. Five months after implantation, his clinical status remained impaired (left ventricular ejection fraction = 30 %). The SonR signal amplitude had also decreased from 0.52 g to 0.29 g. Nevertheless, because our patient was no longer presenting with atrial fibrillation, the anti-arrhythmic treatment was stopped and the SonR optimization system was activated. After 2 months of automatic cardiac resynchronization therapy with defibrillator optimization, our patient's clinical status had significantly improved (left ventricular ejection fraction = 60 %, New York Heart Association class II) and the SonR signal amplitude had doubled shortly after the first weekly automatic optimization. In this non-responding patient, device-based automatic cardiac resynchronization therapy optimization was shown to significantly improve his clinical status.

Falcon: automated optimization method for arbitrary assessment criteria

DOEpatents

Yang, Tser-Yuan; Moses, Edward I.; Hartmann-Siantar, Christine

2001-01-01

FALCON is a method for automatic multivariable optimization for arbitrary assessment criteria that can be applied to numerous fields where outcome simulation is combined with optimization and assessment criteria. A specific implementation of FALCON is for automatic radiation therapy treatment planning. In this application, FALCON implements dose calculations into the planning process and optimizes available beam delivery modifier parameters to determine the treatment plan that best meets clinical decision-making criteria. FALCON is described in the context of the optimization of external-beam radiation therapy and intensity modulated radiation therapy (IMRT), but the concepts could also be applied to internal (brachytherapy) radiotherapy. The radiation beams could consist of photons or any charged or uncharged particles. The concept of optimizing source distributions can be applied to complex radiography (e.g. flash x-ray or proton) to improve the imaging capabilities of facilities proposed for science-based stockpile stewardship.

Once-daily fosamprenavir with ritonavir in the treatment of HIV infection in therapy-naïve patients.

PubMed

Flamholc, Leo; Gisslén, Magnus

2008-12-01

Treatment options for HIV patients have dramatically improved since the introduction of efficacious antiretroviral combination therapy more than a decade ago. Treatment regimens have been simplified with fewer pills and fewer daily dosages. Fosamprenavir is a protease inhibitor with a rather long half-life which makes it a candidate for once-daily use. Once-daily dosage of ritonavir-boosted fosamprenavir is approved in the US, but not in Europe, for treatment in patients without prior antiretroviral treatment. Here we review the background and rationale for once-daily dosage of ritonavir-boosted fosamprenavir. The rather limited studies that have been published so far indicate that fosamprenavir 1400 mg may be used once daily boosted with ritonavir. The optimal ritonavir dose to be given together with fosamprenavir is still to be defined, though available results indicate that a dose of 100 mg may be adequate provided that no protease inhibitor resistance is present.

Oral Anticoagulant Therapy

PubMed Central

Gallus, Alexander S.; Wittkowsky, Ann; Crowther, Mark; Hylek, Elaine M.; Palareti, Gualtiero

2012-01-01

Background: The objective of this article is to summarize the published literature concerning the pharmacokinetics and pharmacodynamics of oral anticoagulant drugs that are currently available for clinical use and other aspects related to their management. Methods: We carried out a standard review of published articles focusing on the laboratory and clinical characteristics of the vitamin K antagonists; the direct thrombin inhibitor, dabigatran etexilate; and the direct factor Xa inhibitor, rivaroxaban Results: The antithrombotic effect of each oral anticoagulant drug, the interactions, and the monitoring of anticoagulation intensity are described in detail and discussed without providing specific recommendations. Moreover, we describe and discuss the clinical applications and optimal dosages of oral anticoagulant therapies, practical issues related to their initiation and monitoring, adverse events such as bleeding and other potential side effects, and available strategies for reversal. Conclusions: There is a large amount of evidence on laboratory and clinical characteristics of vitamin K antagonists. A growing body of evidence is becoming available on the first new oral anticoagulant drugs available for clinical use, dabigatran and rivaroxaban. PMID:22315269

Drug Concentration Thresholds Predictive of Therapy Failure and Death in Children With Tuberculosis: Bread Crumb Trails in Random Forests

PubMed Central

Swaminathan, Soumya; Pasipanodya, Jotam G.; Ramachandran, Geetha; Hemanth Kumar, A. K.; Srivastava, Shashikant; Deshpande, Devyani; Nuermberger, Eric; Gumbo, Tawanda

2016-01-01

Background. The role of drug concentrations in clinical outcomes in children with tuberculosis is unclear. Target concentrations for dose optimization are unknown. Methods. Plasma drug concentrations measured in Indian children with tuberculosis were modeled using compartmental pharmacokinetic analyses. The children were followed until end of therapy to ascertain therapy failure or death. An ensemble of artificial intelligence algorithms, including random forests, was used to identify predictors of clinical outcome from among 30 clinical, laboratory, and pharmacokinetic variables. Results. Among the 143 children with known outcomes, there was high between-child variability of isoniazid, rifampin, and pyrazinamide concentrations: 110 (77%) completed therapy, 24 (17%) failed therapy, and 9 (6%) died. The main predictors of therapy failure or death were a pyrazinamide peak concentration <38.10 mg/L and rifampin peak concentration <3.01 mg/L. The relative risk of these poor outcomes below these peak concentration thresholds was 3.64 (95% confidence interval [CI], 2.28–5.83). Isoniazid had concentration-dependent antagonism with rifampin and pyrazinamide, with an adjusted odds ratio for therapy failure of 3.00 (95% CI, 2.08–4.33) in antagonism concentration range. In regard to death alone as an outcome, the same drug concentrations, plus z scores (indicators of malnutrition), and age <3 years, were highly ranked predictors. In children <3 years old, isoniazid 0- to 24-hour area under the concentration-time curve <11.95 mg/L × hour and/or rifampin peak <3.10 mg/L were the best predictors of therapy failure, with relative risk of 3.43 (95% CI, .99–11.82). Conclusions. We have identified new antibiotic target concentrations, which are potential biomarkers associated with treatment failure and death in children with tuberculosis. PMID:27742636

Pharmacokinetics and Pharmacodynamics of Piperacillin-Tazobactam in 42 Patients Treated with Concomitant CRRT

PubMed Central

Bauer, Seth R.; Salem, Charbel; Connor, Michael J.; Groszek, Joseph; Taylor, Maria E.; Wei, Peilin; Tolwani, Ashita J.

2012-01-01

Summary Background and objectives Current recommendations for piperacillin-tazobactam dosing in patients receiving continuous renal replacement therapy originate from studies with relatively few patients and lower continuous renal replacement therapy doses than commonly used today. This study measured the pharmacokinetic and pharmacodynamic characteristics of piperacillin-tazobactam in patients treated with continuous renal replacement therapy using contemporary equipment and prescriptions. Design, setting, participants, & measurements A multicenter prospective observational study in the intensive care units of two academic medical centers was performed, enrolling patients with AKI or ESRD receiving piperacillin-tazobactam while being treated with continuous renal replacement therapy. Pregnant women, children, and patients with end stage liver disease were excluded from enrollment. Plasma and continuous renal replacement therapy effluent samples were analyzed for piperacillin and tazobactam levels using HPLC. Pharmacokinetic and pharmacodynamic parameters were calculated using standard equations. Multivariate analyses were used to examine the association of patient and continuous renal replacement therapy characteristics with piperacillin pharmacokinetic parameters. Results Forty-two of fifty-five subjects enrolled had complete sampling. Volume of distribution (median=0.38 L/kg, intraquartile range=0.20 L/kg) and elimination rate constants (median=0.104 h−1, intraquartile range=0.052 h−1) were highly variable, and clinical parameters could explain only a small fraction of the large variability in pharmacokinetic parameters. Probability of target attainment for piperacillin was 83% for total drug but only 77% when the unbound fraction was considered. Conclusions There is significant patient to patient variability in pharmacokinetic/pharmacodynamic parameters in patients receiving continuous renal replacement therapy. Many patients did not achieve pharmacodynamic targets, suggesting that therapeutic drug monitoring might optimize therapy. PMID:22282479

Method for estimating optimal spectral and energy parameters of laser irradiation in photodynamic therapy of biological tissue

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lisenko, S A; Kugeiko, M M

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 ofmore » 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)« less

Stem cell gene therapy for fanconi anemia: report from the 1st international Fanconi anemia gene therapy working group meeting.

PubMed

Tolar, Jakub; Adair, Jennifer E; Antoniou, Michael; Bartholomae, Cynthia C; Becker, Pamela S; Blazar, Bruce R; Bueren, Juan; Carroll, Thomas; Cavazzana-Calvo, Marina; Clapp, D Wade; Dalgleish, Robert; Galy, Anne; Gaspar, H Bobby; Hanenberg, Helmut; Von Kalle, Christof; Kiem, Hans-Peter; Lindeman, Dirk; Naldini, Luigi; Navarro, Susana; Renella, Raffaele; Rio, Paula; Sevilla, Julián; Schmidt, Manfred; Verhoeyen, Els; Wagner, John E; Williams, David A; Thrasher, Adrian J

2011-07-01

Survival rates after allogeneic hematopoietic cell transplantation (HCT) for Fanconi anemia (FA) have increased dramatically since 2000. However, the use of autologous stem cell gene therapy, whereby the patient's own blood stem cells are modified to express the wild-type gene product, could potentially avoid the early and late complications of allogeneic HCT. Over the last decades, gene therapy has experienced a high degree of optimism interrupted by periods of diminished expectation. Optimism stems from recent examples of successful gene correction in several congenital immunodeficiencies, whereas diminished expectations come from the realization that gene therapy will not be free of side effects. The goal of the 1st International Fanconi Anemia Gene Therapy Working Group Meeting was to determine the optimal strategy for moving stem cell gene therapy into clinical trials for individuals with FA. To this end, key investigators examined vector design, transduction method, criteria for large-scale clinical-grade vector manufacture, hematopoietic cell preparation, and eligibility criteria for FA patients most likely to benefit. The report summarizes the roadmap for the development of gene therapy for FA.

Optimized signal detection and analysis methods for in vivo photoacoustic flow cytometry

NASA Astrophysics Data System (ADS)

Wang, Qiyan; Zhou, Quanyu; Yang, Ping; Wang, Xiaoling; Niu, Zhenyu; Suo, Yuanzhen; He, Hao; Gao, Wenyuan; Tang, Shuo; Wei, Xunbin

2017-02-01

Melanoma is known as a malignant tumor of melanocytes, which usually appear in the blood circulation at the metastasis stage of cancer. Thus the detection of circulating melanoma cells is useful for early diagnosis and therapy of cancer. Here we have developed an in vivo photoacoustic flow cytometry (PAFC) based on the photoacoustic effect to detect melanoma cells. However, the raw signals we obtain from the target cells contain noises such as environmental sonic noises and electronic noises. Therefore we apply correlation comparison and feature separation methods to the detection and verification of the in vivo signals. Due to similar shape and structure of cells, the photoacoustic signals usually have similar vibration mode. By analyzing the correlations and the signal features in time domain and frequency domain, we are able to provide a method for separating photoacoustic signals generated by target cells from background noises. The method introduced here has proved to optimize the signal acquisition and signal processing, which can improve the detection accuracy in PAFC.

Optimal medical treatment versus carotid endarterectomy: the rationale and design of the Aggressive Medical Treatment Evaluation for Asymptomatic Carotid Artery Stenosis (AMTEC) study.

PubMed

Kolos, Igor; Loukianov, Mikhail; Dupik, Nikolay; Boytsov, Sergey; Deev, Alexandr

2015-02-01

Carotid endarterectomy and medical therapy (aspirin) were shown superior to medical therapy alone for asymptomatic (≥ 60%) carotid stenosis. The role of modern medical therapy (statins, antihypertensive treatment, and aspirin) in the treatment of such patients is undefined. Establishing the safety, efficacy, and durability of optimal medical therapy and lifestyle modification requires rigorous comparison with carotid endarterectomy in asymptomatic patients. The objective is to compare the efficacy of carotid endarterectomy + optimal medical therapy versus optimal medical therapy alone in patients with asymptomatic (70-79%) extracranial carotid stenosis. The Aggressive Medical Treatment Evaluation for Asymptomatic Carotid Artery Stenosis study is a prospective, randomized, parallel, two-arm, multicenter trial. Primary end-points will be analyzed using standard time-to-event statistical modeling with adjustment for major baseline covariates. The primary analysis is on an intent-to-treat basis. The primary outcome is nonfatal stroke, nonfatal myocardial infarction, and death during follow-up of up to five-years, and the secondary outcome includes death from any cause and stroke. © 2013 The Authors. International Journal of Stroke © 2013 World Stroke Organization.

Dynamics of hepatitis C under optimal therapy and sampling based analysis

NASA Astrophysics Data System (ADS)

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.

The "COLD-PCR approach" for early and cost-effective detection of tyrosine kinase inhibitor resistance mutations in EGFR-positive non-small cell lung cancer.

PubMed

Mairinger, Fabian D; Vollbrecht, Claudia; Streubel, Anna; Roth, Andreas; Landt, Olfert; Walter, Henry F R; Kollmeier, Jens; Mairinger, Thomas

2014-01-01

Activating epidermal growth factor receptor (EGFR) gene mutations can be successfully treated by EGFR tyrosine kinase inhibitors (EGFR-TKIs), but nearly 50% of all patients' exhibit progression of the disease until treatment because of T790M mutations. It is proposed that this is mostly caused by therapy-resistant tumor clones harboring a T790M mutation. Until now no cost-effective routine-diagnostic method for EGFR-resistance mutation status analysis is available leaving long-time response to TKI treatment to chance. Unambiguous identification of T790M EGFR mutations is mandatory to optimize initial treatment strategies. Artificial EGFR T790M mutations and human wild-type gDNA were prepared in several dilution series. Preferential amplification using coamplification at lower denaturation temperature-PCR (COLD-PCR) of the mutant sequence and subsequent HybProbe melting curve detection or pyrosequencing were performed in comparison to normal processing. COLD-PCR-based amplification allowed the detection of 0.125% T790M mutant DNA in a background of wild-type DNA in comparison to 5% while normal processing. These results were reproducible. COLD-PCR is a powerful and cost-effective tool for routine diagnostic to detect underrepresented tumor clones in clinical samples. A diagnostic tool for unambiguous identification of T790M-mutated minor tumor clones is now available enabling optimized therapy.

Beyond immune checkpoint blockade: new approaches to targeting host-tumor interactions in prostate cancer: report from the 2014 Coffey-Holden prostate cancer academy meeting.

PubMed

Miyahira, Andrea K; Kissick, Haydn T; Bishop, Jennifer L; Takeda, David Y; Barbieri, Christopher E; Simons, Jonathan W; Pienta, Kenneth J; Soule, Howard R

2015-03-01

The 2014 Coffey-Holden Prostate Cancer Academy Meeting, held in La Jolla, CA from June 26 to 29, 2014, was themed: "Beyond Immune Checkpoint Blockade: New Approaches to Targeting Host-Tumor Interactions in Prostate Cancer." Sponsored by the Prostate Cancer Foundation (PCF), this annual, invitation-only meeting is structured as an action-tank, and brought together 72 investigators with diverse academic backgrounds to discuss the most relevant topics in the fields of prostate cancer immunotherapy and the tumor microenvironment. The questions addressed at the meeting included: mechanisms underlying the successes and failures of prostate cancer immunotherapies, how to trigger an effective immune response against prostate cancer, the tumor microenvironment and its role in therapy resistance and tumor metastasis, clinically relevant prostate cancer mouse models, how host-tumor interactions affect current therapies and tumor phenotypes, application of principles of precision medicine to prostate cancer immunotherapy, optimizing immunotherapy clinical trial design, and complex multi-system interactions that affect prostate cancer and immune responses including the effects of obesity and the potential role of the host microbiome. This article highlights the most significant recent progress and unmet needs that were discussed at the meeting toward the goal of speeding the development of optimal immunotherapies for the treatment of prostate cancer. © 2014 Wiley Periodicals, Inc.

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

NASA Astrophysics Data System (ADS)

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, beamlet weight, the number of delivered beamlets, and the number of delivery angles. These methods are evaluated via treatment planning studies including left-sided whole breast irradiation, lung stereotactic body radiotherapy, nasopharyngeal carcinoma, and whole brain radiotherapy with hippocampal avoidance. Improvements in efficiency and efficacy relative to traditional proton therapy and intensity modulated photon radiation therapy are discussed.

Modern concepts in facial nerve reconstruction

PubMed Central

2010-01-01

Background Reconstructive surgery of the facial nerve is not daily routine for most head and neck surgeons. The published experience on strategies to ensure optimal functional results for the patients are based on small case series with a large variety of surgical techniques. On this background it is worthwhile to develop a standardized approach for diagnosis and treatment of patients asking for facial rehabilitation. Conclusion A standardized approach is feasible: Patients with chronic facial palsy first need an exact classification of the palsy's aetiology. A step-by-step clinical examination, if necessary MRI imaging and electromyographic examination allow a classification of the palsy's aetiology as well as the determination of the severity of the palsy and the functional deficits. Considering the patient's desire, age and life expectancy, an individual surgical concept is applicable using three main approaches: a) early extratemporal reconstruction, b) early reconstruction of proximal lesions if extratemporal reconstruction is not possible, c) late reconstruction or in cases of congenital palsy. Twelve to 24 months after the last step of surgical reconstruction a standardized evaluation of the therapeutic results is recommended to evaluate the necessity for adjuvant surgical procedures or other adjuvant procedures, e.g. botulinum toxin application. Up to now controlled trials on the value of physiotherapy and other adjuvant measures are missing to give recommendation for optimal application of adjuvant therapies. PMID:21040532

The Impact of Reporting a Prior Penicillin Allergy on the Treatment of Methicillin-Sensitive Staphylococcus aureus Bacteremia

PubMed Central

Shenoy, Erica S.; Huang, Mingshu; Kuhlen, James L.; Ware, Winston A.; Parker, Robert A.; Walensky, Rochelle P.

2016-01-01

Background Methicillin-sensitive Staphylococcus aureus (MSSA) bacteremia is a morbid infection with mortality benefit from receipt of parenteral β-lactam therapy. A substantial portion of MSSA bacteremia patients report penicillin allergy, but infrequently have true allergy. Objective To determine the frequency and predictors of optimal and adequate therapy in patients with MSSA bacteremia. Design Retrospective cohort. Participants Adult inpatients with MSSA bacteremia, January 2009 through October 2013. Main Measures The primary measure was a trial of optimal therapy (OT), defined as ≥3 inpatient days or discharge on any first-line agents (nafcillin, oxacillin, cefazolin, or penicillin G, if susceptible). The secondary measure was completion of adequate therapy (AT), defined as ≥10 inpatient days or discharge on an agent appropriate for MSSA bacteremia. Data were electronically gathered with key variables manually validated through chart review. Log-binomial regression models were used to determine the frequency and predictors of outcomes. Key Results Of 456 patients, 346 (76%) received a trial of OT. Patients reporting penicillin allergy (13%) were less likely to receive OT trial than those without penicillin allergy (47% vs. 80%, p <0.001). Adjusting for other factors, penicillin allergy was the largest negative predictor of OT trial (RR 0.64 [0.49, 0.83]). Infectious Disease (ID) consultation was the largest positive predictor of OT trial across all patients (RR 1.34 [1.14, 1.57]). Allergy/Immunology consultation was the single most important predictor of OT trial among patients reporting penicillin allergy (RR 2.33 [1.44, 3.77]). Of 440 patients, 391 (89%) completed AT, with ID consultation the largest positive predictor of the outcome (RR 1.28 [1.15, 1.43]). Conclusions Nearly 25% of patients with MSSA bacteremia did not receive OT trial and about 10% did not receive AT completion. Reported penicillin allergy reduced, and ID consult increased, the likelihood of OT. Allergy evaluation, coupled with ID consultation, may improve outcomes in MSSA bacteremic patients. PMID:27438379

The 'Harmonizing Optimal Strategy for Treatment of coronary artery stenosis - sAfety & effectiveneSS of drug-elUting stents & antiplatelet REgimen' (HOST-ASSURE) trial: study protocol for a randomized controlled trial

PubMed Central

2012-01-01

Background Second-generation drug-eluting stents (DES) have raised the bar of clinical performance. These stents are mostly made from cobalt chromium alloy. A newer generation DES has been developed from platinum chromium alloy, but clinical data regarding the efficacy and safety of the platinum chromium-based everolimus-eluting stent (PtCr-EES) is limited, with no comparison data against the cobalt chromium-based zotarolimus-eluting stent (CoCr-ZES). In addition, an antiplatelet regimen is an integral component of medical therapy after percutaneous coronary intervention (PCI). A 1-week duration of doubling the dose of clopidogrel (double-dose antiplatelet therapy (DDAT)) was shown to improve outcome at 1 month compared with conventional dose in acute coronary syndrome (ACS) patients undergoing PCI. However in Asia, including Korea, the addition of cilostazol (triplet antiplatelet therapy (TAT)) is used more commonly than doubling the dose of clopidogrel in high-risk patients. Methods In the 'Harmonizing Optimal Strategy for Treatment of coronary artery stenosis - sAfety & effectiveneSS of drug-elUting stents & antiplatelet REgimen' (HOST-ASSURE) trial, approximately 3,750 patients are being prospectively and randomly assigned in a 2 × 2 factorial design according to the type of stent (PtCr-EES vs CoCr-ZES) and antiplatelet regimen (TAT vs DDAT). The first primary endpoint is target lesion failure at 1 year for the stent comparison, and the second primary endpoint is net clinical outcome at 1 month for comparison of antiplatelet therapy regimen. Discussion The HOST-ASSURE trial is the largest study yet performed to directly compare the efficacy and safety of the PtCr-EES versus CoCr-ZES in an 'all-comers' population. In addition, this study will also compare the clinical outcome of TAT versus DDAT for 1-month post PCI. Trial registration ClincalTrials.gov number NCT01267734. PMID:22463698

Is Dosing of Therapeutic Immunoglobulins Optimal? A Review of a Three-Decade Long Debate in Europe

PubMed Central

Kerr, Jacqueline; Quinti, Isabella; Eibl, Martha; Chapel, Helen; Späth, Peter J.; Sewell, W. A. Carrock; Salama, Abdulgabar; van Schaik, Ivo N.; Kuijpers, Taco W.; Peter, Hans-Hartmut

2014-01-01

The consumption of immunoglobulins (Ig) is increasing due to better recognition of antibody deficiencies, an aging population, and new indications. This review aims to examine the various dosing regimens and research developments in the established and in some of the relevant off-label indications in Europe. The background to the current regulatory settings in Europe is provided as a backdrop for the latest developments in primary and secondary immunodeficiencies and in immunomodulatory indications. In these heterogeneous areas, clinical trials encompassing different routes of administration, varying intervals, and infusion rates are paving the way toward more individualized therapy regimens. In primary antibody deficiencies, adjustments in dosing and intervals will depend on the clinical presentation, effective IgG trough levels and IgG metabolism. Ideally, individual pharmacokinetic profiles in conjunction with the clinical phenotype could lead to highly tailored treatment. In practice, incremental dosage increases are necessary to titrate the optimal dose for more severely ill patients. Higher intravenous doses in these patients also have beneficial immunomodulatory effects beyond mere IgG replacement. Better understanding of the pharmacokinetics of Ig therapy is leading to a move away from simplistic “per kg” dosing. Defective antibody production is common in many secondary immunodeficiencies irrespective of whether the causative factor was lymphoid malignancies (established indications), certain autoimmune disorders, immunosuppressive agents, or biologics. This antibody failure, as shown by test immunization, may be amenable to treatment with replacement Ig therapy. In certain immunomodulatory settings [e.g., idiopathic thrombocytopenic purpura (ITP)], selection of patients for Ig therapy may be enhanced by relevant biomarkers in order to exclude non-responders and thus obtain higher response rates. In this review, the developments in dosing of therapeutic immunoglobulins have been limited to high and some medium priority indications such as ITP, Kawasaki’ disease, Guillain–Barré syndrome, chronic inflammatory demyelinating polyradiculoneuropathy, myasthenia gravis, multifocal motor neuropathy, fetal alloimmune thrombocytopenia, fetal hemolytic anemia, and dermatological diseases. PMID:25566244

Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 Clinical Guidelines for the Management of Adults with Major Depressive Disorder

PubMed Central

Quilty, Lena C.; Ravitz, Paula; Rosenbluth, Michael; Pavlova, Barbara; Grigoriadis, Sophie; Velyvis, Vytas; Kennedy, Sidney H.; Lam, Raymond W.; MacQueen, Glenda M.; Milev, Roumen V.; Ravindran, Arun V.; Uher, Rudolf

2016-01-01

Background: The Canadian Network for Mood and Anxiety Treatments (CANMAT) has revised its 2009 guidelines for the management of major depressive disorder (MDD) in adults by updating the evidence and recommendations. The target audiences for these 2016 guidelines are psychiatrists and other mental health professionals. Methods: Using the question-answer format, we conducted a systematic literature search focusing on systematic reviews and meta-analyses. Evidence was graded using CANMAT-defined criteria for level of evidence. Recommendations for lines of treatment were based on the quality of evidence and clinical expert consensus. “Psychological Treatments” is the second of six sections of the 2016 guidelines. Results: Evidence-informed responses were developed for 25 questions under 5 broad categories: 1) patient characteristics relevant to using psychological interventions; 2) therapist and health system characteristics associated with optimizing outcomes; 3) descriptions of major psychotherapies and their efficacy; 4) additional psychological interventions, such as peer interventions and computer- and technology-delivered interventions; and 5) combining and/or sequencing psychological and pharmacological interventions. Conclusions: First-line psychological treatment recommendations for acute MDD include cognitive-behavioural therapy (CBT), interpersonal therapy (IPT), and behavioural activation (BA). Second-line recommendations include computer-based and telephone-delivered psychotherapy. Where feasible, combining psychological treatment (CBT or IPT) with antidepressant treatment is recommended because combined treatment is superior to either treatment alone. First-line psychological treatments for maintenance include CBT and mindfulness-based cognitive therapy (MBCT). Patient preference, in combination with evidence-based treatments and clinician/system capacity, will yield the optimal treatment strategies for improving individual outcomes in MDD. PMID:27486150

Spinal Cord Stimulation in Chronic Pain: Mode of Action.

PubMed

Vallejo, Ricardo; Bradley, Kerry; Kapural, Leonardo

2017-07-15

Literature review. A review of the literature that presents a perspective on mechanisms of actions behind spinal cord stimulation (SCS) therapy for chronic pain. SCS is an effective therapeutic alternative for the treatment of intractable chronic pain. Its application has been mostly based on the gate control theory of pain. Computational models have been fundamental on the understanding of clinical observations and the design of therapies that provide optimal neuromodulation. Research has provided insight into the involvement of specific neurotransmitters that support segmental and supraspinal mechanisms of action. A literature review was performed with emphasis on mechanisms of action for SCS including the effects of electrical fields on spinal cord structures based on computational models and preclinical and clinical explorations. This review provides background on the development of SCS, which has been driven around a paresthesia-based paradigm as a result of the gate control theory. A review of computational models emphasizes their importance on our current understanding of the mechanism of action and clinical optimization of therapy. Electrophysiology and molecular biology have provided a closer, yet narrow, view of the effect of SCS on neurotransmitters and their receptors, which have led to the formulation of segmental and supraspinal mechanisms. Literature supporting the involvement of glial cells in chronic pain and their characteristic response to electrical fields should motivate further investigation of mechanisms involving neuroglia. Finally, a review of recent results paresthesia-free strategies should encourage research on mechanisms of action. The mechanisms of SCS have been extensively studied and several consistent phenomena have emerged. The activation of A-beta fibers to induce paresthesia also involve neurotransmitter release via segmental and supraspinal pathways. Despite advancements, much remains to be understood, particularly as new stimulation strategies are developed. N /A.

Management of ceritinib therapy and adverse events in patients with ALK-rearranged non-small cell lung cancer.

PubMed

Califano, Raffaele; Greystoke, Alastair; Lal, Rohit; Thompson, Joyce; Popat, Sanjay

2017-09-01

Anaplastic lymphoma kinase rearrangement (ALK+) occurs in approximately 2-7% of patients with non-small cell lung cancer (NSCLC), contributing to a considerable number of patients with ALK+ NSCLC worldwide. Ceritinib is a next generation ALK inhibitor (ALKi), approved by the European Medicines Agency in 2015. In the first-in-human, phase I study, ceritinib demonstrated rapid and durable responses in ALK patients previously treated with a different ALKi and in those who were ALKi-naive. As ceritinib is starting to be used routinely for the treatment of patients with ALK+ NSCLC, experience is growing with regard to ideal therapy management. In this review we provide a brief background to the development of ceritinib. The optimal treatment management and adverse events associated with ceritinib in clinical trials and in clinical practice are then discussed in detail, and where applicable, an expert consensus on specific recommendations are made. In clinical trials, the most common adverse events related to ceritinib are nausea, vomiting, and diarrhea. However, the majority of these are mild and, in the opinion of the authors, can be effectively managed with dose modifications. Based on clinical data, ceritinib has demonstrated efficacy as a first-line therapy and in patients who have relapsed on crizotinib, including those with brain metastases at baseline. Unfortunately, at some point, all patients experience progressive disease, with the central nervous system being a common site of metastases. Recommendations are made for continuing treatment beyond disease progression as long as a clinical benefit to patients is observed. Here, we review management of ceritinib treatment and adverse events and make recommendations on optimal management of patients. Copyright © 2017. Published by Elsevier B.V.

Practice Patterns and Trends in the Use of Medical Therapy in Patients Undergoing Percutaneous Coronary Intervention in Ontario

PubMed Central

Garg, Pallav; Wijeysundera, Harindra C.; Yun, Lingsong; Cantor, Warren J.; Ko, Dennis T.

2014-01-01

Background Clinical guidelines emphasize medical therapy as the initial approach to the management of patients with stable coronary artery disease (CAD). However, the extent to which medical therapy is applied before and after percutaneous coronary intervention (PCI) in contemporary clinical practice is uncertain. We evaluated medication use for patients with stable CAD undergoing PCI, and assessed whether the COURAGE study altered medication use in the Canadian healthcare system. Methods and Results A population‐based cohort of 23 680 older patients >65 years old) with stable CAD undergoing PCI in Ontario between 2003 and 2010 was assembled. Optimal medical therapy (OMT) was defined as prescription for a β‐blocker, statin, and either angiotensin‐converting enzyme inhibitor or angiotensin II receptor blocker in the 90 days before PCI, and the same medications plus thienopyridine 90 days following PCI. Prior to PCI, 8023 (33.9%) patients were receiving OMT, 11 891 (50.2%) were on suboptimal therapy, and 3766 (15.9%) were not prescribed any medications of interest. There was significant improvement in medical therapy following PCI (OMT: 11 149 [47.1%], suboptimal therapy: 11 591 [48.9%], and none: 940 [4.0%], P<0.001). Utilization rate of OMT reduced significantly after the publication of COURAGE (34.9% before versus 32.8% after, P<0.001). Similarly, the rate of OMT following PCI was lower in the period after publication of COURAGE (47.3% before versus 46.9% after, P<0.001). Conclusions OMT was prescribed in about 1 in 3 patients prior to PCI and less than half after PCI. In contrast to the anticipated impact of COURAGE, we found lower rates of medication use in PCI patients after its publication. PMID:25122664

Stroke Treatment Academic Industry Roundtable

PubMed Central

Jovin, Tudor G.; Albers, Gregory W.; Liebeskind, David S.

2017-01-01

Background and Purpose The STAIR (Stroke Treatment Academic Industry Roundtable) meeting aims to advance acute stroke therapy development through collaboration between academia, industry, and regulatory institutions. In pursuit of this goal and building on recently available level I evidence of benefit from endovascular therapy (ET) in large vessel occlusion stroke, STAIR IX consensus recommendations were developed that outline priorities for future research in ET. Methods Three key directions for advancing the field were identified: (1) development of systems of care for ET in large vessel occlusion stroke, (2) development of therapeutic approaches adjunctive to ET, and (3) exploring clinical benefit of ET in patient population insufficiently studied in recent trials. Methodological issues such as optimal trial design and outcome measures have also been addressed. Results Development of systems of care strategies should be geared both toward ensuring broad access to ET for eligible patients and toward shortening time to reperfusion to the minimum possible. Adjunctive therapy development includes neuroprotective approaches, adjuvant microcirculatory/collateral enhancing strategies, and periprocedural management. Future research priorities seeking to expand the eligible patient population are to determine benefit of ET in patients presenting beyond conventional time windows, in patients with large baseline ischemic core lesions, and in other important subgroups. Conclusions Research priorities in ET for large vessel occlusion stroke are to improve systems of care, investigate effective adjuvant therapies, and explore whether patient eligibility could be expanded. PMID:27586682

Targeting EGFR with photodynamic therapy in combination with Erbitux enhances in vivo bladder tumor response

PubMed Central

Bhuvaneswari, Ramaswamy; Gan, Yik Yuen; Soo, Khee Chee; Olivo, Malini

2009-01-01

Background Photodynamic therapy (PDT) is a promising cancer treatment modality that involves the interaction of the photosensitizer, molecular oxygen and light of specific wavelength to destroy tumor cells. Treatment induced hypoxia is one of the main side effects of PDT and efforts are underway to optimize PDT protocols for improved efficacy. The aim of this study was to investigate the anti-tumor effects of PDT plus Erbitux, an angiogenesis inhibitor that targets epidermal growth factor receptor (EGFR), on human bladder cancer model. Tumor-bearing nude mice were assigned to four groups that included control, PDT, Erbitux and PDT plus Erbitux and tumor volume was charted over 90-day period. Results Our results demonstrate that combination of Erbitux with PDT strongly inhibits tumor growth in the bladder tumor xenograft model when compared to the other groups. Downregulation of EGFR was detected using immunohistochemistry, immunofluorescence and western blotting. Increased apoptosis was associated with tumor inhibition in the combination therapy group. In addition, we identified the dephosphorylation of ErbB4 at tyrosine 1284 site to play a major role in tumor inhibition. Also, at the RNA level downregulation of EGFR target genes cyclin D1 and c-myc was observed in tumors treated with PDT plus Erbitux. Conclusion The combination therapy of PDT and Erbitux effectively inhibits tumor growth and is a promising therapeutic approach in the treatment of bladder tumors. PMID:19878607

The proton therapy nozzles at Samsung Medical Center: A Monte Carlo simulation study using TOPAS

NASA Astrophysics Data System (ADS)

Chung, Kwangzoo; Kim, Jinsung; Kim, Dae-Hyun; Ahn, Sunghwan; Han, Youngyih

2015-07-01

To expedite the commissioning process of the proton therapy system at Samsung Medical Center (SMC), we have developed a Monte Carlo simulation model of the proton therapy nozzles by using TOol for PArticle Simulation (TOPAS). At SMC proton therapy center, we have two gantry rooms with different types of nozzles: a multi-purpose nozzle and a dedicated scanning nozzle. Each nozzle has been modeled in detail following the geometry information provided by the manufacturer, Sumitomo Heavy Industries, Ltd. For this purpose, the novel features of TOPAS, such as the time feature or the ridge filter class, have been used, and the appropriate physics models for proton nozzle simulation have been defined. Dosimetric properties, like percent depth dose curve, spreadout Bragg peak (SOBP), and beam spot size, have been simulated and verified against measured beam data. Beyond the Monte Carlo nozzle modeling, we have developed an interface between TOPAS and the treatment planning system (TPS), RayStation. An exported radiotherapy (RT) plan from the TPS is interpreted by using an interface and is then translated into the TOPAS input text. The developed Monte Carlo nozzle model can be used to estimate the non-beam performance, such as the neutron background, of the nozzles. Furthermore, the nozzle model can be used to study the mechanical optimization of the design of the nozzle.

[Generalized tendomyopathy (fibromyalgia): differential diagnosis, therapy and prognosis].

PubMed

Schmidt, K L

1991-08-01

The generalised tendomyopathy is one of the most variegated and fascinating disease of man. The unusual constellation and combination of symptoms constrain to the differential-diagnostic demarcation of a great number of rheumatic and non-rheumatic diseases. While the rheumatic polymyalgia and myositis are easily to be demarcated, the decision between a primary and secondary generalised tendomyopathy can be difficult. In individual cases a classical tendomyopathy can be accompanied by antinuclear factors and then it is at the earliest a "collagenosis the state of waiting". The therapy of tendomyopathy is altogether unsatisfactory. All forms of therapy (medicamentous, physical, psychotherapy) help at the utmost in 50%. Surprisingly, on the part of the medicaments the non-steroidal antiphlogistic drugs and the glucocorticoids in most cases completely fail, and also the physical therapy is frequently not tolerated and/or has only a short duration of effect. The more important are the influence on possible evoking factors, the optimization of the social background and the utilization of the possibilities of the "secondary prevention" (balneotherapy in a health resort, sauna bath, Kneipp's applications, change of the living and working conditions, easy sports activities). Since the disease is frequent, but not yet known in general, it should be made better acquainted among the physicians. The generalised tendomyopathy is and remains a cardinal problem not only of rheumatology, but of the physician's working-day in general.

Subspace-based optimization method for inverse scattering problems with an inhomogeneous background medium

NASA Astrophysics Data System (ADS)

Chen, Xudong

2010-07-01

This paper proposes a version of the subspace-based optimization method to solve the inverse scattering problem with an inhomogeneous background medium where the known inhomogeneities are bounded in a finite domain. Although the background Green's function at each discrete point in the computational domain is not directly available in an inhomogeneous background scenario, the paper uses the finite element method to simultaneously obtain the Green's function at all discrete points. The essence of the subspace-based optimization method is that part of the contrast source is determined from the spectrum analysis without using any optimization, whereas the orthogonally complementary part is determined by solving a lower dimension optimization problem. This feature significantly speeds up the convergence of the algorithm and at the same time makes it robust against noise. Numerical simulations illustrate the efficacy of the proposed algorithm. The algorithm presented in this paper finds wide applications in nondestructive evaluation, such as through-wall imaging.

[Utilization of Occupational Therapy in Children - Results from the KiGGS Basis Survey].

PubMed

Weber, A; Karch, D; Thyen, U; Rommel, A; Schlack, R; Hölling, H; von Kries, R

2016-03-01

A population-based analysis on use of occupational therapy by child's parentally reported health restrictions and socio-demographic determinants is missing. The basis KiGGS survey (2003 to 2006) reports on health in 17 641 children aged 0 to 17 years. The use of occupational therapy in the last 12 months could be ticked as other therapies with a free text field to name occupational therapy or others. Health restrictions potentially relevant for the use of occupational therapy and sociodemographic factors were assessed. The proportion of use of occupational therapy explained by the health restrictions was estimated by the population attributable risk fraction. The average use of occupational therapy for 3 to 13-year-olds was 2.4%. There was no association with the socioeconomic status; Children with immigration background used occupational therapy less often (e. g. age group 3 to 6 years: ORadjusted 0.2 [95-% KI: 0.1-1.0]). The proportion of occupational therapy explainable by the health restrictions considered ranged from 45% (3 to 6 years) to 65% (11 to 13 years). The lower use of occupational therapy in the KiGGS survey compared to health insurance reports may be explained by the ascertainment method. A lower use of occupational therapy related to immigration background matches lower use for physician visits. The causes for the low proportion of explained occupational therapy in young children and the lower use in children with immigration background warrant further research. © Georg Thieme Verlag KG Stuttgart · New York.

Stem Cell Gene Therapy for Fanconi Anemia: Report from the 1st International Fanconi Anemia Gene Therapy Working Group Meeting

PubMed Central

Tolar, Jakub; Adair, Jennifer E; Antoniou, Michael; Bartholomae, Cynthia C; Becker, Pamela S; Blazar, Bruce R; Bueren, Juan; Carroll, Thomas; Cavazzana-Calvo, Marina; Clapp, D Wade; Dalgleish, Robert; Galy, Anne; Gaspar, H Bobby; Hanenberg, Helmut; Von Kalle, Christof; Kiem, Hans-Peter; Lindeman, Dirk; Naldini, Luigi; Navarro, Susana; Renella, Raffaele; Rio, Paula; Sevilla, Julián; Schmidt, Manfred; Verhoeyen, Els; Wagner, John E; Williams, David A; Thrasher, Adrian J

2011-01-01

Survival rates after allogeneic hematopoietic cell transplantation (HCT) for Fanconi anemia (FA) have increased dramatically since 2000. However, the use of autologous stem cell gene therapy, whereby the patient's own blood stem cells are modified to express the wild-type gene product, could potentially avoid the early and late complications of allogeneic HCT. Over the last decades, gene therapy has experienced a high degree of optimism interrupted by periods of diminished expectation. Optimism stems from recent examples of successful gene correction in several congenital immunodeficiencies, whereas diminished expectations come from the realization that gene therapy will not be free of side effects. The goal of the 1st International Fanconi Anemia Gene Therapy Working Group Meeting was to determine the optimal strategy for moving stem cell gene therapy into clinical trials for individuals with FA. To this end, key investigators examined vector design, transduction method, criteria for large-scale clinical-grade vector manufacture, hematopoietic cell preparation, and eligibility criteria for FA patients most likely to benefit. The report summarizes the roadmap for the development of gene therapy for FA. PMID:21540837

Evaluation of the theory-based Quality Improvement in Physical Therapy (QUIP) programme: a one-group, pre-test post-test pilot study

PubMed Central

2013-01-01

Background Guideline adherence in physical therapy is far from optimal, which has consequences for the effectiveness and efficiency of physical therapy care. Programmes to enhance guideline adherence have, so far, been relatively ineffective. We systematically developed a theory-based Quality Improvement in Physical Therapy (QUIP) programme aimed at the individual performance level (practicing physiotherapists; PTs) and the practice organization level (practice quality manager; PQM). The aim of the study was to pilot test the multilevel QUIP programme’s effectiveness and the fidelity, acceptability and feasibility of its implementation. Methods A one-group, pre-test, post-test pilot study (N = 8 practices; N = 32 PTs, 8 of whom were also PQMs) done between September and December 2009. Guideline adherence was measured using clinical vignettes that addressed 12 quality indicators reflecting the guidelines’ main recommendations. Determinants of adherence were measured using quantitative methods (questionnaires). Delivery of the programme and management changes were assessed using qualitative methods (observations, group interviews, and document analyses). Changes in adherence and determinants were tested in the paired samples T-tests and expressed in effect sizes (Cohen’s d). Results Overall adherence did not change (3.1%; p = .138). Adherence to three quality indicators improved (8%, 24%, 43%; .000 ≤ p ≤ .023). Adherence to one quality indicator decreased (−15.7%; p = .004). Scores on various determinants of individual performance improved and favourable changes at practice organizational level were observed. Improvements were associated with the programme’s multilevel approach, collective goal setting, and the application of self-regulation; unfavourable findings with programme deficits. The one-group pre-test post-test design limits the internal validity of the study, the self-selected sample its external validity. Conclusions The QUIP programme has the potential to change physical therapy practice but needs considerable revision to induce the ongoing quality improvement process that is required to optimize overall guideline adherence. To assess its value, the programme needs to be tested in a randomized controlled trial. PMID:23705912

Poster — Thur Eve — 61: A new framework for MPERT plan optimization using MC-DAO

DOE Office of Scientific and Technical Information (OSTI.GOV)

Baker, M; Lloyd, S AM; Townson, R

2014-08-15

This work combines the inverse planning technique known as Direct Aperture Optimization (DAO) with Intensity Modulated Radiation Therapy (IMRT) and combined electron and photon therapy plans. In particular, determining conditions under which Modulated Photon/Electron Radiation Therapy (MPERT) produces better dose conformality and sparing of organs at risk than traditional IMRT plans is central to the project. Presented here are the materials and methods used to generate and manipulate the DAO procedure. Included is the introduction of a powerful Java-based toolkit, the Aperture-based Monte Carlo (MC) MPERT Optimizer (AMMO), that serves as a framework for optimization and provides streamlined access tomore » underlying particle transport packages. Comparison of the toolkit's dose calculations to those produced by the Eclipse TPS and the demonstration of a preliminary optimization are presented as first benchmarks. Excellent agreement is illustrated between the Eclipse TPS and AMMO for a 6MV photon field. The results of a simple optimization shows the functioning of the optimization framework, while significant research remains to characterize appropriate constraints.« less

Multifaceted antibiotic treatment analysis of methicillin-sensitive Staphylococcus aureus bloodstream infections.

PubMed

Weber, Zhanni; Ariano, Robert; Lagacé-Wiens, Philippe; Zelenitsky, Sheryl

2016-12-01

Given the overall prevalence and poor prognosis of Staphylococcus aureus bloodstream infections (BSIs), the study of treatment strategies to improve patient outcomes is important. The aim of this study was to conduct a multifaceted antibiotic treatment analysis of methicillin-sensitive S. aureus (MSSA) BSI and to characterise optimal early antibiotic therapy (within the first 7 days of drawing the index blood culture) for this serious infection. Antibiotic selection was categorised as optimal targeted (intravenous cloxacillin or cefazolin), optimal broad (piperacillin/tazobactam or meropenem), adequate (vancomycin) or inadequate (other antibiotics or oral therapy). A TSE (timing, selection, exposure) score was developed to comprehensively characterise early antibiotic therapy, where higher points corresponded to prompt initiation, optimal antibiotic selection and longer exposure (duration). Amongst 71 cases of complicated MSSA-BSI, end-of-treatment (EOT) response (i.e. clinical cure) was improved when at least adequate antibiotic therapy was initiated within 24 h [71.7% (33/46) vs. 48.0% (12/25); P = 0.047]. Clinical cure was also more likely when therapy included ≥4 days of optimal targeted antibiotics within the first 7 days [74.4% (29/39) vs. 50.0% (16/32); P = 0.03]. The TSE score was an informative index of early antibiotic therapy, with EOT cure documented in 72.0% (36/50) compared with 42.9% (9/21) of cases with scores above and below 15.2, respectively (P = 0.02). In multivariable analysis, lower Charlson comorbidity index, presence of BSI on admission, and optimising early antibiotic therapy, as described above, were associated with clinical cure in patients with MSSA-BSI. Copyright © 2016 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

Predicting optimal response to B-cell depletion with rituximab in multiple sclerosis using CXCL13 index, magnetic resonance imaging and clinical measures

PubMed Central

Alvarez, Enrique; Piccio, Laura; Mikesell, Robert J; Trinkaus, Kathryn; Parks, Becky J; Naismith, Robert T

2015-01-01

Background B-cell depleting drugs show promise for treating multiple sclerosis. Objective We sought predictors of optimal response to rituximab, a B-cell depleting antibody, to help guide therapy selection. Methods We performed a post hoc study of 30 relapsing multiple sclerosis patients with breakthrough disease while on beta-interferon or glatiramer acetate who were treated with add-on rituximab. Standardized neurologic examinations, brain magnetic resonance imaging, and cerebrospinal fluid were obtained before and after rituximab. Tissue biomarkers were measured. Optimal responders were defined as having no evidence of disease activity. Results At baseline, optimal responders with no evidence of disease activity had higher IgG indices (P = 0.041), and higher CXCL13 indices ((cerebrospinal fluid CXCL13/serum CXCL13)/albumin index; P = 0.024), more contrast enhancing lesions (P = 0.002), better 25 foot timed walk (P = 0.001), and Expanded Disability Status Scale (P = 0.002). Rituximab treatment led to reduced cerebrospinal fluid biomarkers of tissue destruction: myelin basic protein (P = 0.046), neurofilament light chain (P < 0.001), and of inflammation (CXCL13 index; P = 0.042). Conclusions Multiple sclerosis patients with optimal response to rituximab had higher cerebrospinal fluid IgG and CXCL13 indices, more gadolinium-enhancing lesions, and less disability at baseline. Rituximab treatment led to decreased markers of inflammation and tissue damage. If validated, these results will help identify multiple sclerosis patients who will respond optimally to B-cell depletion. PMID:28607711

Impact of Pharmacy Practice Model Expansion on Pharmacokinetic Services: Optimization of Vancomycin Dosing and Improved Patient Safety.

PubMed

Han, Zhe; Pettit, Natasha N; Landon, Emily M; Brielmaier, Benjamin D

2017-04-01

Background: The impact of pharmacy interventions on optimizing vancomycin therapy has been described, however interventions vary among studies and the most optimal pharmacy practice model (PPM) for pharmacokinetic (PK) services has not been established. Objective: The purpose of this study is to demonstrate the value of 24 hours a day, 7 days a week (24/7) PK services. Methods: New PK services were implemented in 2 phases with institutional PPM expansion. Phase 1 included universal monitoring by pharmacists with recommendations made to prescribers during business hours. Phase 2 expanded clinical pharmacists' coverage to 24/7 and provided an optional 24/7 pharmacist-managed PK consult service. We compared vancomycin therapeutic trough attainment, dosing, and clinical and safety outcomes between phases 1 and 2 in adult inpatients receiving therapeutic intravenous vancomycin. Results. One hundred and fifty patients were included in each phase. Phase 2 had a greater proportion of vancomycin courses with therapeutic initial trough concentrations (27.5% vs 46.1%; p = 0.002), higher initial trough concentrations (10.9 mcg/mL vs 16.4 mcg/mL; p < 0.001), and optimized initial vancomycin dosing (13.5 mg/kg vs 16.2 mg/kg; p < 0.001). Phase 2 also saw significant reduction in the incidence of vancomycin-associated nephrotoxicity (21.1% vs 11.7%; p = 0.038). Dose optimization and improvement in initial target trough attainment were most notable among intensive care unit (ICU) patients. Conclusions. Our study demonstrated that 24/7 PK services implemented with institutional PPM expansion optimized vancomycin target trough attainment and improved patient safety.

Optimal control of malaria: combining vector interventions and drug therapies.

PubMed

Khamis, Doran; El Mouden, Claire; Kura, Klodeta; Bonsall, Michael B

2018-04-24

The sterile insect technique and transgenic equivalents are considered promising tools for controlling vector-borne disease in an age of increasing insecticide and drug-resistance. Combining vector interventions with artemisinin-based therapies may achieve the twin goals of suppressing malaria endemicity while managing artemisinin resistance. While the cost-effectiveness of these controls has been investigated independently, their combined usage has not been dynamically optimized in response to ecological and epidemiological processes. An optimal control framework based on coupled models of mosquito population dynamics and malaria epidemiology is used to investigate the cost-effectiveness of combining vector control with drug therapies in homogeneous environments with and without vector migration. The costs of endemic malaria are weighed against the costs of administering artemisinin therapies and releasing modified mosquitoes using various cost structures. Larval density dependence is shown to reduce the cost-effectiveness of conventional sterile insect releases compared with transgenic mosquitoes with a late-acting lethal gene. Using drug treatments can reduce the critical vector control release ratio necessary to cause disease fadeout. Combining vector control and drug therapies is the most effective and efficient use of resources, and using optimized implementation strategies can substantially reduce costs.

Optimization of HAART with genetic algorithms and agent-based models of HIV infection.

PubMed

Castiglione, F; Pappalardo, F; Bernaschi, M; Motta, S

2007-12-15

Highly Active AntiRetroviral Therapies (HAART) can prolong life significantly to people infected by HIV since, although unable to eradicate the virus, they are quite effective in maintaining control of the infection. However, since HAART have several undesirable side effects, it is considered useful to suspend the therapy according to a suitable schedule of Structured Therapeutic Interruptions (STI). In the present article we describe an application of genetic algorithms (GA) aimed at finding the optimal schedule for a HAART simulated with an agent-based model (ABM) of the immune system that reproduces the most significant features of the response of an organism to the HIV-1 infection. The genetic algorithm helps in finding an optimal therapeutic schedule that maximizes immune restoration, minimizes the viral count and, through appropriate interruptions of the therapy, minimizes the dose of drug administered to the simulated patient. To validate the efficacy of the therapy that the genetic algorithm indicates as optimal, we ran simulations of opportunistic diseases and found that the selected therapy shows the best survival curve among the different simulated control groups. A version of the C-ImmSim simulator is available at http://www.iac.cnr.it/~filippo/c-ImmSim.html

Pharmacodynamics of nicotine: implications for rational treatment of nicotine addiction.

PubMed

Benowitz, N L

1991-05-01

Rational treatment of the pharmacologic aspects of tobacco addiction includes nicotine substitution therapy. Understanding the pharmacodynamics of nicotine and its role in the addiction process provides a basis for rational therapeutic intervention. Pharmacodynamic considerations are discussed in relation to the elements of smoking cessation therapy: setting objectives, selecting appropriate medication and dosing form, selecting the optimal doses and dosage regimens, assessing therapeutic outcome, and adjusting therapy to optimize benefits and minimize risks.

Economic evaluation of strategies for restarting anticoagulation therapy after a first event of unprovoked venous thromboembolism.

PubMed

Monahan, M; Ensor, J; Moore, D; Fitzmaurice, D; Jowett, S

2017-08-01

Essentials Correct duration of treatment after a first unprovoked venous thromboembolism (VTE) is unknown. We assessed when restarting anticoagulation was worthwhile based on patient risk of recurrent VTE. When the risk over a one-year period is 17.5%, restarting is cost-effective. However, sensitivity analyses indicate large uncertainty in the estimates. Background Following at least 3 months of anticoagulation therapy after a first unprovoked venous thromboembolism (VTE), there is uncertainty about the duration of therapy. Further anticoagulation therapy reduces the risk of having a potentially fatal recurrent VTE but at the expense of a higher risk of bleeding, which can also be fatal. Objective An economic evaluation sought to estimate the long-term cost-effectiveness of using a decision rule for restarting anticoagulation therapy vs. no extension of therapy in patients based on their risk of a further unprovoked VTE. Methods A Markov patient-level simulation model was developed, which adopted a lifetime time horizon with monthly time cycles and was from a UK National Health Service (NHS)/Personal Social Services (PSS) perspective. Results Base-case model results suggest that treating patients with a predicted 1 year VTE risk of 17.5% or higher may be cost-effective if decision makers are willing to pay up to £20 000 per quality adjusted life year (QALY) gained. However, probabilistic sensitivity analysis shows that the model was highly sensitive to overall parameter uncertainty and caution is warranted in selecting the optimal decision rule on cost-effectiveness grounds. Univariate sensitivity analyses indicate variables such as anticoagulation therapy disutility and mortality risks were very influential in driving model results. Conclusion This represents the first economic model to consider the use of a decision rule for restarting therapy for unprovoked VTE patients. Better data are required to predict long-term bleeding risks during therapy in this patient group. © 2017 International Society on Thrombosis and Haemostasis.

Why Neck Pain Patients Are Not Referred to Manual Therapy: A Qualitative Study among Dutch Primary Care Stakeholders

PubMed Central

Dikkers, Marije F.; Westerman, Marjan J.; Rubinstein, Sidney M.; van Tulder, Maurits W.; Anema, Johannes R.

2016-01-01

Background Treatment of neck pain with manual therapy demonstrated to be more effective and cost-effective than general practitioner (GP) care or physiotherapy in a high quality RCT in the Netherlands in 2002. However, referral to manual therapy for neck pain is still relatively low. This study aims to explore the barriers and facilitators affecting the implementation of manual therapy in neck pain management in primary care. Methods An explorative study was conducted comprising semi-structured interviews with GPs (n = 13), physiotherapists (n = 10), manual therapists (n = 7) and their patients with neck pain (n = 27), and three focus groups with additional stakeholders (n = 10–12 per group). A thematic analysis approach was used. Results Different barriers and facilitators for referral were found for patients, GPs and physiotherapists on the individual level, but also in the interaction between stakeholders and their context. Individual perceptions such as knowledge and beliefs about manual therapy for neck pain either impeded or facilitated referral. Fear for complications associated with cervical manipulation was an important barrier for patients as well as GPs. For GPs and physiotherapists it was important whether they perceived it was part of their professional role to refer for manual therapy. Existing relations formed referral behavior, and the trust in a particular practitioner was a recurrent theme among GPs and physiotherapist as well as patients. The contextual factor availability of manual therapy played a role for all stakeholders. Conclusions Barriers and facilitators were found especially in individual perceptions on manual therapy for neck pain (e.g. knowledge and beliefs), the interaction between stakeholders (e.g. collaboration and trust) and the organizational context. Implementation strategies that focus on these different aspects seem to be likely to optimize referral rates and the use of manual therapy in primary care management of neck pain. PMID:27311067

Outcomes of Optimized over Standard Protocol of Rabbit Antithymocyte Globulin for Severe Aplastic Anemia: A Single-Center Experience

PubMed Central

Ge, Meili; Shao, Yingqi; Huang, Jinbo; Huang, Zhendong; Zhang, Jing; Nie, Neng; Zheng, Yizhou

2013-01-01

Background Previous reports showed that outcome of rabbit antithymocyte globulin (rATG) was not satisfactory as the first-line therapy for severe aplastic anemia (SAA). We explored a modifying schedule of administration of rATG. Design and Methods Outcomes of a cohort of 175 SAA patients, including 51 patients administered with standard protocol (3.55 mg/kg/d for 5 days) and 124 cases with optimized protocol (1.97 mg/kg/d for 9 days) of rATG plus cyclosporine (CSA), were analyzed retrospectively. Results Of all 175 patients, response rates at 3 and 6 months were 36.6% and 56.0%, respectively. 51 cases received standard protocol had poor responses at 3 (25.5%) and 6 months (41.2%). However, 124 patients received optimized protocol had better responses at 3 (41.1%, P = 0.14) and 6 (62.1%, P = 0.01). Higher incidences of infection (57.1% versus 37.9%, P = 0.02) and early mortality (17.9% versus 0.8%, P<0.001) occurred in patients received standard protocol compared with optimized protocol. The 5-year overall survival in favor of the optimized over standard rATG protocol (76.0% versus. 50.3%, P<0.001) was observed. By multivariate analysis, optimized protocol (RR = 2.21, P = 0.04), response at 3 months (RR = 10.31, P = 0.03) and shorter interval (<23 days) between diagnosis and initial dose of rATG (RR = 5.35, P = 0.002) were independent favorable predictors of overall survival. Conclusions Optimized instead of standard rATG protocol in combination with CSA remained efficacious as a first-line immunosuppressive regimen for SAA. PMID:23554855

The development of targeted new agents to improve the outcome for children with leukemia.

PubMed

Bautista, Francisco; Van der Lugt, Jasper; Kearns, Pamela R; Mussai, Francis J; Zwaan, C Michel; Moreno, Lucas

2016-11-01

Survival rates in pediatric leukemia have greatly improved in the last decades but still a substantial number of patients will relapse and die. New agents are necessary to overcome the limitations of conventional chemotherapy and hematopoietic stem cell transplantation and to reduce their undesirable long-term toxicities. The identification of driving molecular alterations of leukemogenesis in subsets of patients will allow the incorporation of new-targeted therapies. Areas covered: In this article the authors present a detailed review of the most recent advances in targeted therapies for pediatric leukemias. A comprehensive description of the biological background, adult data and early clinical trials in pediatrics is provided. Expert opinion: Clinical trials are the way to evaluate new agents in pediatric cancer. The development of new drugs in pediatric leukemia must be preceded by a solid biological rationale. Agents in development exploit all possible vulnerabilities of leukemic cells. Drugs targeting cell surface antigens, intracellular signaling pathways and cell cycle inhibitors or epigenetic regulators are most prominent. Major advances have occurred thanks to new developments in engineering leading to optimized molecules such as anti-CD19 bi-specific T-cell engagers (e.g. blinatumomab) and antibody-drug conjugates. The integration of new-targeted therapies in pediatric chemotherapy-based regimens will lead to improved outcomes.

New Receptor Targets for Medical Therapy in Irritable Bowel Syndrome

PubMed Central

Camilleri, Michael

2010-01-01

Background Despite setbacks to the approval of new medications for the treatment of irritable bowel syndrome, interim guidelines on endpoints for IBS trials have enhanced interest as new targets for medical therapy are proposed based on novel mechanisms or chemical entities. Aim To review the approved lubiprostone, two targets that are not meeting expectations (tachykinins and corticotrophin-releasing hormone), the efficacy and safety of new 5-HT4 agonists, intestinal secretagogues (chloride channel activators, and guanylate cyclase-C agonists), bile acid modulation, anti-inflammatory agents and visceral analgesics. Methods Review of selected articles based on PubMed search and clinically relevant information on mechanism of action, safety, pharmacodynamics, and efficacy Conclusions The spectrum of peripheral targets of medical therapy address chiefly the bowel dysfunction of IBS, and these effects are associated with pain relief. There are less clear targets related to the abdominal pain or visceral sensation in IBS. The new 5-HT4 agonists are more specific than older agents, and show cardiovascular safety to date. Secretory agents have high specificity, low bioavailability, and efficacy. The potential risks of agents “borrowed” from other indications (like hyperlipidemia, inflammatory bowel disease or somatic pain) deserve further study. There is reason for optimism in medical treatment of IBS. PMID:19785622

Development of Sendai Virus Vectors and their Potential Applications in Gene Therapy and Regenerative Medicine

PubMed Central

Nakanishi, Mahito; Otsu, Makoto

2012-01-01

Gene delivery/expression vectors have been used as fundamental technologies in gene therapy since the 1980s. These technologies are also being applied in regenerative medicine as tools to reprogram cell genomes to a pluripotent state and to other cell lineages. Rapid progress in these new research areas and expectations for their translation into clinical applications have facilitated the development of more sophisticated gene delivery/expression technologies. Since its isolation in 1953 in Japan, Sendai virus (SeV) has been widely used as a research tool in cell biology and in industry, but the application of SeV as a recombinant viral vector has been investigated only recently. Recombinant SeV vectors have various unique characteristics, such as low pathogenicity, powerful capacity for gene expression and a wide host range. In addition, the cytoplasmic gene expression mediated by this vector is advantageous for applications, in that chromosomal integration of exogenous genes can be undesirable. In this review, we introduce a brief historical background on the development of recombinant SeV vectors and describe their current applications in gene therapy. We also describe the application of SeV vectors in advanced nuclear reprogramming and introduce a defective and persistent SeV vector (SeVdp) optimized for such reprogramming. PMID:22920683

Evaluation and management of patients with heart disease and cancer: cardio-oncology.

PubMed

Herrmann, Joerg; Lerman, Amir; Sandhu, Nicole P; Villarraga, Hector R; Mulvagh, Sharon L; Kohli, Manish

2014-09-01

The care for patients with cancer has advanced greatly over the past decades. A combination of earlier cancer diagnosis and greater use of traditional and new systemic treatments has decreased cancer-related mortality. Effective cancer therapies, however, can result in short- and long-term comorbidities that can decrease the net clinical gain by affecting quality of life and survival. In particular, cardiovascular complications of cancer treatments can have a profound effect on the health of patients with cancer and are more common among those with recognized or unrecognized underlying cardiovascular diseases. A new discipline termed cardio-oncology has thus evolved to address the cardiovascular needs of patients with cancer and optimize their care in a multidisciplinary approach. This review provides a brief introduction and background on this emerging field and then focuses on its practical aspects including cardiovascular risk assessment and prevention before cancer treatment, cardiovascular surveillance and therapy during cancer treatment, and cardiovascular monitoring and management after cancer therapy. The content of this review is based on a literature search of PubMed between January 1, 1960, and February 1, 2014, using the search terms cancer, cardiomyopathy, cardiotoxicity, cardio-oncology, chemotherapy, heart failure, and radiation. Copyright © 2014 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

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

PubMed

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

2017-01-07

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.

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

NASA Astrophysics Data System (ADS)

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.

A New Approach to Integrate GPU-based Monte Carlo Simulation into Inverse Treatment Plan Optimization for Proton Therapy

PubMed Central

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

2016-01-01

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. PMID:27991456

Experiences of international students from Asian backgrounds studying occupational therapy in Australia.

PubMed

Lim, Jung Wook; Honey, Anne; Du Toit, Sanet; Chen, Yu-Wei; Mackenzie, Lynette

2016-10-01

International students from culturally and linguistically diverse backgrounds experience personal and academic challenges when studying health sciences in Australia. Given recent discussions about cultural specificity in occupational therapy and its status as an emerging profession in most Asian countries, this study aimed to explore and describe the experiences of international students from Asian backgrounds studying occupational therapy in Australia. A phenomenological approach was used to understand the experiences of participants. In-depth interviews were conducted with eight international occupational therapy students from Asian countries studying in Australia. Data were analysed using hermeneutic methods. Participants described three interlinked and ongoing experiences: (1) Discovering and engaging with occupational therapy; (2) Fitting into my new role; and (3) Anticipating my role at home. Whilst theoretical aspects of occupational therapy were seen as compatible with participants' home cultures, application was seen as problematic due to the differences in structure and institutional culture of the healthcare systems. Although students made adaptations to fit in as occupational therapy students in Australia, they continued to see themselves as different, and their adaptation also influenced how they saw themselves in relation to their home culture. Findings can contribute to creating culturally sensitive education for occupational therapy students from Asian countries. To best serve these students, educators should consider ways to facilitate transitions both out of and back into students' home cultures. © 2016 Occupational Therapy Australia.

Night Blood Pressure Responses to Atenolol and Hydrochlorothiazide in Black and White Patients With Essential Hypertension

PubMed Central

2014-01-01

BACKGROUND Night blood pressure (BP) predicts patient outcomes. Variables associated with night BP response to antihypertensive agents have not been fully evaluated in essential hypertension. METHODS We sought to measure night BP responses to hydrochlorothiazide (HCTZ), atenolol (ATEN), and combined therapy using ambulatory blood pressure (ABP) monitoring in 204 black and 281 white essential hypertensive patients. Initial therapy was randomized; HCTZ and ATEN once daily doses were doubled after 3 weeks and continued for 6 more weeks with the alternate medication added for combined therapy arms. ABP was measured at baseline and after completion of each drug. Night, day, and night/day BP ratio responses (treatment − baseline) were compared in race/sex subgroups. RESULTS Baseline night systolic BP and diastolic BP, and night/day ratios were greater in blacks than whites (P < 0.01, all comparisons). Night BP responses to ATEN were absent and night/day ratios increased significantly in blacks (P < 0.05). At the end of combined therapy, women, blacks, and those starting with HCTZ as opposed to ATEN had significantly greater night BP responses (P < 0.01). Variables that significantly associated with ATEN response differed from those that associated with HCTZ response and those that associated with night BP response differed from those that associated with day BP response. CONCLUSIONS In summary, after completion of HCTZ and ATEN therapy, women, blacks, and those who started with HCTZ had greater night BP responses. Reduced night BP response and increased night/day BP ratios occured with ATEN in blacks. Given the prognostic significance of night BP, strategies for optimizing night BP antihypertensive therapy should be considered. CLINICAL TRIAL REGISTRATION Clinicaltrials.gov identifier NCT00246519 PMID:23886594

Parenteral and oral antibiotic duration for treatment of pediatric osteomyelitis: a systematic review protocol

PubMed Central

2013-01-01

Background Pediatric osteomyelitis is a bacterial infection of bones requiring prolonged antibiotic treatment using parenteral followed by enteral agents. Major complications of pediatric osteomyelitis include transition to chronic osteomyelitis, formation of subperiosteal abscesses, extension of infection into the joint, and permanent bony deformity or limb shortening. Historically, osteomyelitis has been treated with long durations of antibiotics to avoid these complications. However, with improvements in management and antibiotic treatment, standard of care is moving towards short durations of intravenous antibiotics prior to enteral antibiotics. Methods/Design The authors will perform a systematic review based on PRISMA guidelines in order to evaluate the literature, looking for evidence to support the optimal duration of parenteral and enteral therapy. The main goals are to see if literature supports shorter durations of either parenteral antibiotics and/or enteral antibiotics. Multiple databases will be investigated using a thorough search strategy. Databases include Medline, Cochrane, EMBASE, SCOPUS, Dissertation Abstracts, CINAHL, Web of Science, African Index Medicus and LILACS. Search stream will include medical subject heading for pediatric patients with osteomyelitis and antibiotic therapy. We will search for published or unpublished randomized and quasi-randomized controlled trials. Two authors will independently select articles, extract data and assess risk of bias by standard Cochrane methodologies. We will analyze comparisons between dichotomous outcomes using risk ratios and continuous outcomes using mean differences. 95% confidence intervals will be computed. Discussion One of the major dilemmas of management of this disease is the duration of parenteral therapy. Long parenteral therapy has increased risk of serious complications and the necessity for long therapy has been called into question. Our study aims to review the currently available evidence from randomized trials regarding duration of both parenteral and oral therapy for pediatric acute osteomyelitis. Trial registration CRD42013002320 PMID:24099135

Comparing Linguistic Complexity and Efficiency in Conversations from Stimulation and Conversation Therapy in Aphasia

ERIC Educational Resources Information Center

Savage, Meghan C.; Donovan, Neila J.

2017-01-01

Background: Efficacy studies have demonstrated the benefit of group conversation therapy for a person with aphasia (PWA). However, a PWA typically participates in individual therapy prior to group therapy. Stimulation therapy (ST) is the most common type of individual aphasia therapy. Ultimately, the outcome of therapy is to enable the PWA to…

Is systems pharmacology ready to impact upon therapy development? A study on the cholesterol biosynthesis pathway

PubMed Central

Benson, Helen E; Sharman, Joanna L; Mpamhanga, Chido P; Parton, Andrew; Southan, Christopher; Harmar, Anthony J; Ghazal, Peter

2017-01-01

Background and Purpose An ever‐growing wealth of information on current drugs and their pharmacological effects is available from online databases. As our understanding of systems biology increases, we have the opportunity to predict, model and quantify how drug combinations can be introduced that outperform conventional single‐drug therapies. Here, we explore the feasibility of such systems pharmacology approaches with an analysis of the mevalonate branch of the cholesterol biosynthesis pathway. Experimental Approach Using open online resources, we assembled a computational model of the mevalonate pathway and compiled a set of inhibitors directed against targets in this pathway. We used computational optimization to identify combination and dose options that show not only maximal efficacy of inhibition on the cholesterol producing branch but also minimal impact on the geranylation branch, known to mediate the side effects of pharmaceutical treatment. Key Results We describe serious impediments to systems pharmacology studies arising from limitations in the data, incomplete coverage and inconsistent reporting. By curating a more complete dataset, we demonstrate the utility of computational optimization for identifying multi‐drug treatments with high efficacy and minimal off‐target effects. Conclusion and Implications We suggest solutions that facilitate systems pharmacology studies, based on the introduction of standards for data capture that increase the power of experimental data. We propose a systems pharmacology workflow for the refinement of data and the generation of future therapeutic hypotheses. PMID:28910500

Concept for individualized patient allocation: ReCompare—remote comparison of particle and photon treatment plans

PubMed Central

2014-01-01

Background Identifying those patients who have a higher chance to be cured with fewer side effects by particle beam therapy than by state-of-the-art photon therapy is essential to guarantee a fair and sufficient access to specialized radiotherapy. The individualized identification requires initiatives by particle as well as non-particle radiotherapy centers to form networks, to establish procedures for the decision process, and to implement means for the remote exchange of relevant patient information. In this work, we want to contribute a practical concept that addresses these requirements. Methods We proposed a concept for individualized patient allocation to photon or particle beam therapy at a non-particle radiotherapy institution that bases on remote treatment plan comparison. We translated this concept into the web-based software tool ReCompare (REmote COMparison of PARticlE and photon treatment plans). Results We substantiated the feasibility of the proposed concept by demonstrating remote exchange of treatment plans between radiotherapy institutions and the direct comparison of photon and particle treatment plans in photon treatment planning systems. ReCompare worked with several tested standard treatment planning systems, ensured patient data protection, and integrated in the clinical workflow. Conclusions Our concept supports non-particle radiotherapy institutions with the patient-specific treatment decision on the optimal irradiation modality by providing expertise from a particle therapy center. The software tool ReCompare may help to improve and standardize this personalized treatment decision. It will be available from our website when proton therapy is operational at our facility. PMID:24548333

Model-Based Sensor-Augmented Pump Therapy

PubMed Central

Grosman, Benyamin; Voskanyan, Gayane; Loutseiko, Mikhail; Roy, Anirban; Mehta, Aloke; Kurtz, Natalie; Parikh, Neha; Kaufman, Francine R.; Mastrototaro, John J.; Keenan, Barry

2013-01-01

Background In insulin pump therapy, optimization of bolus and basal insulin dose settings is a challenge. We introduce a new algorithm that provides individualized basal rates and new carbohydrate ratio and correction factor recommendations. The algorithm utilizes a mathematical model of blood glucose (BG) as a function of carbohydrate intake and delivered insulin, which includes individualized parameters derived from sensor BG and insulin delivery data downloaded from a patient’s pump. Methods A mathematical model of BG as a function of carbohydrate intake and delivered insulin was developed. The model includes fixed parameters and several individualized parameters derived from the subject’s BG measurements and pump data. Performance of the new algorithm was assessed using n = 4 diabetic canine experiments over a 32 h duration. In addition, 10 in silico adults from the University of Virginia/Padova type 1 diabetes mellitus metabolic simulator were tested. Results The percentage of time in glucose range 80–180 mg/dl was 86%, 85%, 61%, and 30% using model-based therapy and [78%, 100%] (brackets denote multiple experiments conducted under the same therapy and animal model), [75%, 67%], 47%, and 86% for the control experiments for dogs 1 to 4, respectively. The BG measurements obtained in the simulation using our individualized algorithm were in 61–231 mg/dl min–max envelope, whereas use of the simulator’s default treatment resulted in BG measurements 90–210 mg/dl min–max envelope. Conclusions The study results demonstrate the potential of this method, which could serve as a platform for improving, facilitating, and standardizing insulin pump therapy based on a single download of data. PMID:23567006

Subthalamic Nucleus Deep Brain Stimulation in Early Stage Parkinson’s Disease

PubMed Central

Charles, David; Konrad, Peter E.; Neimat, Joseph S.; Molinari, Anna L.; Tramontana, Michael G.; Finder, Stuart G.; Gill, Chandler E.; Bliton, Mark J.; Kao, Chris C.; Phibbs, Fenna T.; Hedera, Peter; Salomon, Ronald M.; Cannard, Kevin R.; Wang, Lily; Song, Yanna; Davis, Thomas L.

2014-01-01

Background Deep brain stimulation (DBS) is an effective and approved therapy for advanced Parkinson’s disease (PD), and a recent study suggests efficacy in mid-stage disease. This manuscript reports the results of a pilot trial investigating preliminary safety and tolerability of DBS in early PD. Methods Thirty subjects with idiopathic PD (Hoehn & Yahr Stage II off medication), age 50–75, on medication ≥ 6 months but < 4 years, and without motor fluctuations or dyskinesias were randomized to optimal drug therapy (ODT) (n=15) or DBS+ODT (n=15). Co-primary endpoints were the time to reach a 4-point worsening from baseline in the UPDRS-III off therapy and the change in levodopa equivalent daily dose from baseline to 24 months. Results As hypothesized, the mean UPDRS total and part III scores were not significantly different on or off therapy at 24 months. The DBS+ODT group took less medication at all time points, and this reached maximum difference at 18 months. With a few exceptions, differences in neuropsychological functioning were not significant. Two subjects in the DBS+ODT group suffered serious adverse events; remaining adverse events were mild or transient. Conclusions This study demonstrates that subjects with early stage PD will enroll in and complete trials testing invasive therapies and provides preliminary evidence that DBS is well tolerated in early PD. The results of this trial provide the data necessary to design a large, phase III, double-blind, multicenter trial investigating the safety and efficacy of DBS in early PD. PMID:24768120

The effect of a dual or a triple antithrombotic therapy with apixaban on thrombus formation in vivo and in an ex vivo perfusion chamber model

PubMed Central

Weisshaar, Stefan; Litschauer, Brigitte; Bucher, Sebastian; Riesenhuber, Martin; Kapiotis, Stylianos; Kyrle, Paul Alexander; Wolzt, Michael

2016-01-01

Abstract Background: There is a need to optimize pharmacological treatment in patients with acute coronary syndrome and concomitant atrial fibrillation, in particular with newer antithrombotic medicines. We have therefore studied if dual or triple combination of antithrombotic agents exert similar effects on coagulation activation in an in vivo model in the skin microvasculature and in an ex vivo perfusion chamber. Methods and Results: Shed blood platelet activation (β-thromboglobulin [β-TG]), thrombin generation (thrombin-antithrombin complex [TAT]) and volume as well as markers of thrombus size (D-dimer) and its platelet content (P-selectin) in a perfusion chamber were studied in a sequential, open-label, parallel group trial in 40 healthy male volunteers (n = 20 per group). Subjects received ticagrelor and apixaban without or with acetylsalicylic acid (ASA). Outcome parameters were assessed at 3 hours after therapy dosing, and at steady-state trough and peak conditions. A triple or dual therapy induced a comparable decrease in shed blood β-TG at 3 hours after therapy dosing but was more pronounced at steady-state conditions with the more intense treatment combination. During both antithrombotic regimens a similarly sustained inhibition in thrombin generation was observed which was accompanied by comparable increases in shed blood volume. In contrast, no treatment effect could be observed in the perfusion chamber experiment. Conclusion: Ticagrelor and apixaban with or without ASA inhibit platelet activation and thrombin formation in vivo in healthy subjects. Platelet inhibition was greater at steady-state conditions after triple therapy administration. PMID:27399131

Divergent and convergent evolution in metastases suggest treatment strategies based on specific metastatic sites

PubMed Central

Cunningham, Jessica J.; Brown, Joel S.; Vincent, Thomas L.

2015-01-01

Background and objective: Systemic therapy for metastatic cancer is currently determined exclusively by the site of tumor origin. Yet, there is increasing evidence that the molecular characteristics of metastases significantly differ from the primary tumor. We define the evolutionary dynamics of metastases that govern this molecular divergence and examine their potential contribution to variations in response to targeted therapies. Methodology: Darwinian interactions of transformed cells with the tissue microenvironments at primary and metastatic sites are analyzed using evolutionary game theory. Computational models simulate responses to targeted therapies in different organs within the same patient. Results: Tumor cells, although maximally fit at their primary site, typically have lower fitness on the adaptive landscapes offered by the metastatic sites due to organ-specific variations in mesenchymal properties and signaling pathways. Clinically evident metastases usually exhibit time-dependent divergence from the phenotypic mean of the primary population as the tumor cells evolve and adapt to their new circumstances. In contrast, tumors from different primary sites evolving on identical metastatic adaptive landscapes exhibit phenotypic convergence. Thus, metastases in the liver from different primary tumors and even in different hosts will evolve toward similar adaptive phenotypes. The combination of evolutionary divergence from the primary cancer phenotype and convergence towards similar adaptive strategies in the same tissue cause significant variations in treatment responses particularly for highly targeted therapies. Conclusion and implications: The results suggest that optimal therapies for disseminated cancer must take into account the site(s) of metastatic growth as well as the primary organ. PMID:25794501

NEMA NU 4-Optimized Reconstructions for Therapy Assessment in Cancer Research with the Inveon Small Animal PET/CT System.

PubMed

Lasnon, Charline; Dugue, Audrey Emmanuelle; Briand, Mélanie; Blanc-Fournier, Cécile; Dutoit, Soizic; Louis, Marie-Hélène; Aide, Nicolas

2015-06-01

We compared conventional filtered back-projection (FBP), two-dimensional-ordered subsets expectation maximization (OSEM) and maximum a posteriori (MAP) NEMA NU 4-optimized reconstructions for therapy assessment. Varying reconstruction settings were used to determine the parameters for optimal image quality with two NEMA NU 4 phantom acquisitions. Subsequently, data from two experiments in which nude rats bearing subcutaneous tumors had received a dual PI3K/mTOR inhibitor were reconstructed with the NEMA NU 4-optimized parameters. Mann-Whitney tests were used to compare mean standardized uptake value (SUV(mean)) variations among groups. All NEMA NU 4-optimized reconstructions showed the same 2-deoxy-2-[(18)F]fluoro-D-glucose ([(18)F]FDG) kinetic patterns and detected a significant difference in SUV(mean) relative to day 0 between controls and treated groups for all time points with comparable p values. In the framework of therapy assessment in rats bearing subcutaneous tumors, all algorithms available on the Inveon system performed equally.

The Effect of an Attachment-Based Behaviour Therapy for Children with Visual and Severe Intellectual Disabilities

ERIC Educational Resources Information Center

Sterkenburg, P. S.; Janssen, C. G. C.; Schuengel, C.

2008-01-01

Background: A combination of an attachment-based therapy and behaviour modification was investigated for children with persistent challenging behaviour. Method: Six clients with visual and severe intellectual disabilities, severe challenging behaviour and with a background of pathogenic care were treated. Challenging behaviour was recorded…

[Dual Antiplatelet Therapy in the Perioperative Period - To Continue or Discontinue Treatment?

PubMed

Koscielny, Jürgen; von Heymann, Christian; Zeymer, Uwe; Cremer, Jochen; Spannagl, Michael; Labenz, Joachim; Giannitsis, Evangelos; Goss, Franz

2017-08-01

Background  For secondary prevention of acute coronary syndrome, guidelines recommend dual antiplatelet therapy (DAPT) with acetylsalicylic acid and a P2Y12 receptor antagonist such as clopidogrel, prasugrel or ticagrelor for a period of 12 months. Often, uncertainty exists with respect to surgical or diagnostic procedures in these high-risk patients: can the DAPT be continued without interruption? If not, what is the recommended withdrawal strategy? What should be considered for the perioperative management? Methods  An interdisciplinary group of experienced experts in the fields of cardiology, cardiac surgery, gastroenterology, anaesthesiology, intensive care and haemostaseology developed recommendations relevant to daily clinical practice based on the current scientific evidence. Results  These recommendations include instructions for evaluating the patient- and procedure-specific risks of bleeding and ischaemia, general recommendations regarding the DAPT withdrawal strategy, and specific guidance for frequent surgical or diagnostic procedures. Discussion  This article aims to facilitate the management of patients with DAPT for all medical disciplines involved, thereby ensuring optimal care of patients during the perioperative period. © Georg Thieme Verlag KG Stuttgart · New York.

Vision Therapy News Backgrounder.

ERIC Educational Resources Information Center

American Optometric Association, St. Louis, MO.

The booklet provides an overview on vision therapy to aid writers, editors, and broadcasters help parents, teachers, older adults, and all consumers learn more about vision therapy. Following a description of vision therapy or vision training, information is provided on how and why vision therapy works. Additional sections address providers of…

Tracheal bioengineering: the next steps. Proceeds of an International Society of Cell Therapy Pulmonary Cellular Therapy Signature Series Workshop, Paris, France, April 22, 2014.

PubMed

Weiss, Daniel J; Elliott, Martin; Jang, Queenie; Poole, Brian; Birchall, Martin

2014-12-01

There has been significant and exciting recent progress in the development of bioengineering approaches for generating tracheal tissue that can be used for congenital and acquired tracheal diseases. This includes a growing clinical experience in both pediatric and adult patients with life-threatening tracheal diseases. However, not all of these attempts have been successful, and there is ongoing discussion and debate about the optimal approaches to be used. These include considerations of optimal materials, particularly use of synthetic versus biologic scaffolds, appropriate cellularization of the scaffolds, optimal surgical approaches and optimal measure of both clinical and biologic outcomes. To address these issues, the International Society of Cell Therapy convened a first-ever meeting of the leading clinicians and tracheal biologists, along with experts in regulatory and ethical affairs, to discuss and debate the issues. A series of recommendations are presented for how to best move the field ahead. Copyright © 2014 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Intensity of Renal Support in Critically Ill Patients with Acute Kidney Injury

PubMed Central

2008-01-01

BACKGROUND The optimal intensity of renal-replacement therapy in critically ill patients with acute kidney injury is controversial. METHODS We randomly assigned critically ill patients with acute kidney injury and failure of at least one nonrenal organ or sepsis to receive intensive or less intensive renal-replacement therapy. The primary end point was death from any cause by day 60. In both study groups, hemodynamically stable patients underwent intermittent hemodialysis, and hemodynamically unstable patients underwent continuous venovenous hemodiafiltration or sustained low-efficiency dialysis. Patients receiving the intensive treatment strategy underwent intermittent hemodialysis and sustained low-efficiency dialysis six times per week and continuous venovenous hemodiafiltration at 35 ml per kilogram of body weight per hour; for patients receiving the less-intensive treatment strategy, the corresponding treatments were provided thrice weekly and at 20 ml per kilogram per hour. RESULTS Baseline characteristics of the 1124 patients in the two groups were similar. The rate of death from any cause by day 60 was 53.6% with intensive therapy and 51.5% with less-intensive therapy (odds ratio, 1.09; 95% confidence interval, 0.86 to 1.40; P = 0.47). There was no significant difference between the two groups in the duration of renalreplacement therapy or the rate of recovery of kidney function or nonrenal organ failure. Hypotension during intermittent dialysis occurred in more patients randomly assigned to receive intensive therapy, although the frequency of hemodialysis sessions complicated by hypotension was similar in the two groups. CONCLUSIONS Intensive renal support in critically ill patients with acute kidney injury did not decrease mortality, improve recovery of kidney function, or reduce the rate of nonrenal organ failure as compared with less-intensive therapy involving a defined dose of intermittent hemodialysis three times per week and continuous renal-replacement therapy at 20 ml per kilogram per hour. (ClinicalTrials.gov number, NCT00076219.) PMID:18492867

Manipulation of host factors optimizes the pathogenesis of western equine encephalitis virus infections in mice for antiviral drug development.

PubMed

Blakely, Pennelope K; Delekta, Phillip C; Miller, David J; Irani, David N

2015-02-01

While alphaviruses spread naturally via mosquito vectors, some can also be transmitted as aerosols making them potential bioterrorism agents. One such pathogen, western equine encephalitis virus (WEEV), causes fatal human encephalitis via multiple routes of infection and thus presumably via multiple mechanisms. Although WEEV also produces acute encephalitis in non-human primates, a small animal model that recapitulates features of human disease would be useful for both pathogenesis studies and to evaluate candidate antiviral therapies. We have optimized conditions to infect mice with a low passage isolate of WEEV, thereby allowing detailed investigation of virus tropism, replication, neuroinvasion, and neurovirulence. We find that host factors strongly influence disease outcome, and in particular, that age, gender, and genetic background all have significant effects on disease susceptibility independent of virus tropism or replication within the central nervous system. Our data show that experimental variables can be adjusted in mice to recapitulate disease features known to occur in both non-human primates and humans, thus aiding further study of WEEV pathogenesis and providing a realistic therapeutic window for antiviral drug delivery.

Manipulation of host factors optimizes the pathogenesis of western equine encephalitis virus infections in mice for antiviral drug development

PubMed Central

Blakely, Pennelope K.; Delekta, Phillip C.; Miller, David J.; Irani, David N.

2014-01-01

While alphaviruses spread naturally via mosquito vectors, some can also be transmitted as aerosols making them potential bioterrorism agents. One such pathogen, western equine encephalitis virus (WEEV), causes fatal human encephalitis via multiple routes of infection and thus presumably via multiple mechanisms. Although WEEV also produces acute encephalitis in non-human primates, a small animal model that recapitulates features of human disease would be useful for both pathogenesis studies and to evaluate candidate antiviral therapies. We have optimized conditions to infect mice with a low passage isolate of WEEV, thereby allowing detailed investigation of virus tropism, replication, neuroinvasion, and neurovirulence. We find that host factors strongly influence disease outcome, and in particular that age, gender and genetic background all have significant effects on disease susceptibility independent of virus tropism or replication within the central nervous system. Our data show that experimental variables can be adjusted in mice to recapitulate disease features known to occur in both non-human primates and humans, thus aiding further study of WEEV pathogenesis and providing a realistic therapeutic window for antiviral drug delivery. PMID:25361697

Impact of optimal anticoagulation therapy on chronic venous ulcer healing in thrombophilic patients with post-thrombotic syndrome.

PubMed

Hinojosa, C A; Olivares-Cruz, S; Laparra-Escareno, H; Sanchez-Castro, S; Tamayo-Garcia, B; Anaya-Ayala, J E

2016-12-02

Post-thrombotic syndrome (PTS) is the long-term sequelae of deep venous thrombosis (DVT). PTS clinical manifestations include chronic leg pain, oedema, lipodermatosclerosis and ulcers. The objective of this study is to determine in patients with documented history of thrombophilias and DVT whether the number of previous thrombotic events and optimal anticoagulation therapy are associated with the time to venous ulcer healing following the start of compression therapy. Retrospective analysis performed in thrombophilic patients under the age of 50 years old with chronic venous ulcers secondary to DVT at the wound clinic in the National Institute of Medical Sciences and Nutrition 'Salvador Zubirán ' in Mexico City. Variables such as the number or episodes of thrombotic events, type of hypercoagulable disorder, optimal anticoagulation therapy with Warfarin monitored by therapeutic International Normalised Ratio (INR) (2-3) and compliance to compression therapy were examined. Patients that underwent superficial or perforator vein interruption or endovascular recanalisation of deep veins were excluded from the study. From a database of 29 patients with chronic venous ulcers followed in our clinic from January 1992 to September 2012, only 13 patients (61% female) met the inclusion criteria. Mean age±standard deviation (SD) was 32±12 years old. Of these, seven (54%) patients with suboptimal INR presented with an average of two previous thrombotic events and the remaining six (46%) patients with optimal INR only one event (p=0.28), the mean time to the clinical manifestation of a venous ulcer after the first episode of DVT was 39 months (range: 12-72) for patients with suboptimal INR and 82 months (range: 12-216) for those with optimal anticoagulation therapy (p=0.11). During the mean follow-up period of 52 months, all patients in optimal anticoagulation healed their ulcer; their mean time for wound healing was 44 months (range: 4-102). In the suboptimal INR group, only four healed the ulcers with an mean of 72 months (range: 2-204) (p=0.94). There seems to be an association between an optimal anticoagulation therapy with Warfarin monitored by INR and wound healing rates in thrombophilic patients with chronic venous ulcers. Further research is warranted. The authors have no conflict of interest.

Methodologies in the modeling of combined chemo-radiation treatments

NASA Astrophysics Data System (ADS)

Grassberger, C.; Paganetti, H.

2016-11-01

The variety of treatment options for cancer patients has increased significantly in recent years. Not only do we combine radiation with surgery and chemotherapy, new therapeutic approaches such as immunotherapy and targeted therapies are starting to play a bigger role. Physics has made significant contributions to radiation therapy treatment planning and delivery. In particular, treatment plan optimization using inverse planning techniques has improved dose conformity considerably. Furthermore, medical physics is often the driving force behind tumor control and normal tissue complication modeling. While treatment optimization and outcome modeling does focus mainly on the effects of radiation, treatment modalities such as chemotherapy are treated independently or are even neglected entirely. This review summarizes the published efforts to model combined modality treatments combining radiation and chemotherapy. These models will play an increasing role in optimizing cancer therapy not only from a radiation and drug dosage standpoint, but also in terms of spatial and temporal optimization of treatment schedules.

Continuous 4-1BB co-stimulatory signals for the optimal expansion of tumor-infiltrating lymphocytes for adoptive T-cell therapy.

PubMed

Chacon, Jessica Ann; Pilon-Thomas, Shari; Sarnaik, Amod A; Radvanyi, Laszlo G

2013-09-01

Co-stimulation through members of the tumor necrosis factor receptor (TNFR) family appears to be critical for the generation of T cells with optimal effector-memory properties for adoptive cell therapy. Our work suggests that continuous 4-1BB/CD137 co-stimulation is required for the expansion of T cells with an optimal therapeutic profile and that the administration of 4-1BB agonists upon adoptive cell transfer further improves antitumor T-cell functions.

Targeted chelation therapy with EDTA-loaded albumin nanoparticles regresses arterial calcification without causing systemic side effects

PubMed Central

Lei, Yang; Nosoudi, Nasim; Vyavahare, Naren

2014-01-01

Background and aims Elastin-specific medial arterial calcification (MAC) is an arterial disease commonly referred as Monckeberg’s sclerosis. It causes significant arterial stiffness, and as yet, no clinical therapy exists to prevent or reverse it. We developed albumin nanoparticles (NPs) loaded with disodium ethylene diaminetetraacetic acid (EDTA) that were designed to target calcified elastic lamina when administrated by intravenous injection. Methods and Results We optimized NP size, charge, and EDTA-loading efficiency (150~200 nm, zeta potential of − 22.89 ~ − 31.72 mV, loading efficiency for EDTA ~20 %) for in vivo targeting in rats. These NPs released EDTA slowly for up to 5 days. In both ex-vivo study and in vivo study with injury-induced local abdominal aortic calcification, we showed that elastin antibody-coated and EDTA-loaded albumin NPs targeted the damaged elastic lamina while sparing healthy artery. Intravenous NP injections reversed elastin-specific MAC in rats after four injections over a 2-week period. EDTA-loaded albumin NPs did not cause the side effects observed in EDTA injection alone, such as decrease in serum calcium (Ca), increase in urine Ca, or toxicity to kidney. There was no bone loss in any treated groups. Conclusion We demonstrate that elastin antibody-coated and EDTA-loaded albumin NPs might be a promising nanoparticle therapy to reverse elastin-specific MAC and circumvent side effects associated with systemic EDTA chelation therapy. PMID:25285609

Maraviroc (Celsentri) for multidrug-resistant human immunodeficiency virus (HIV)-1.

PubMed

Ndegwa, S

2007-12-01

(1) Maraviroc belongs to a new class of antiretroviral drugs designed to block entry of HIV-1 into CD4+ T-cells via the CCR5 coreceptor. It is indicated for combination therapy in treatment-experienced adults infected with CCR5-tropic HIV-1 that is resistant to multiple antiretroviral agents. (2) Results from two randomized controlled trials (RCTs) indicate that in treatment experienced patients, maraviroc, combined with optimized background therapy (OBT), significantly decreases the level of HIV-1 RNA in the blood (viral load) when compared with OBT alone. The number of patients achieving undetectable viral loads and CD4+ cell count increases were also significantly higher in those receiving maraviroc. (3) Most patients experiencing treatment failure with maraviroc exhibit tropism changes from CCR5-tropic to CXCR4-using virus, but there is no evidence of disease progression. (4) Adverse effects reported with maraviroc include cough, fever, upper respiratory tract infections, rash, muscle and joint pain, abdominal pain, and postural hypotension (dizziness). No significant increases in cardiovascular events, hepatotoxicity, infections or malignancies have been reported with short-term maraviroc therapy. Several post-marketing studies will assess maraviroc's long-term safety for immune function, liver function, malignancy, cardiac events, and risks associated with changes in tropism. (5) Results from an ongoing trial in treatment naive patients suggest that maraviroc may not be superior in terms of viral suppression to standard therapy, but may significantly increase the number of CD4+ T-cells.

Decision-making by surgeons about referral for adjuvant therapy for patients with non-small-cell lung, breast or colorectal cancer: a qualitative study

PubMed Central

Urquhart, Robin; Kendell, Cynthia; Buduhan, Gordon; Rayson, Daniel; Sargeant, Joan; Johnson, Paul; Grunfeld, Eva; Porter, Geoffrey A.

2016-01-01

Background: Because surgeons are the main gatekeepers to oncology services, understanding how they make decisions related to referral for adjuvant therapies is important to optimize referral rates and use of oncology services for patients with potentially curable disease. We examined decision-making by surgeons related to referral to oncology services for patients having undergone curative-intent surgery for non-small-cell lung, breast or colorectal cancer. Methods: We conducted a qualitative study, whose design was guided by the principles of grounded theory. Semi-structured interviews were held with 29 surgeons who performed non-small-cell lung, breast or colorectal cancer surgery in the province of Nova Scotia. Data were collected and analyzed concurrently. Analysis involved an inductive, grounded approach using constant comparative analysis. Data collection and analysis continued until theoretical saturation was reached. Results: Seven factors influenced the surgeons' decision-making related to referral to oncology services: indications and contraindications for therapy; patients' beliefs and preferences; a belief that oncologists are the experts; knowledge of local standards of care; consultation with oncology colleagues; navigating patient logistics (e.g., lodging, caregiving responsibilities, insurance coverage); and system resources and capacity. Interpretation: Our study's findings provide a novel understanding of how surgeons make decisions about oncology referral and point to potential areas for intervention to promote referral to oncology services for patients for whom adjuvant therapy is recommended. PMID:27570760

Optimizing empiric therapy for Gram-negative bloodstream infections in children.

PubMed

Chao, Y; Reuter, C; Kociolek, L K; Patel, R; Zheng, X; Patel, S J

2018-06-01

Antimicrobial stewardship can be challenging in children with bloodstream infections (BSIs) caused by Gram-negative bacilli (GNB). This retrospective cohort study explored how data elements in the electronic health record could potentially optimize empiric antibiotic therapy for BSIs caused by GNB, via the construction of customized antibiograms for categorical GNB infections and identification of opportunities to minimize organism-drug mismatch and decrease time to effective therapy. Our results suggest potential strategies that could be implemented at key decision points in prescribing at initiation, modification, and targeting of therapy. Copyright © 2017 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

Effectiveness of cognitive behavioral therapy on health-related quality of life: An evaluation of therapies provided by trainee therapists.

PubMed

Henriksson, Sophie; Anclair, Malin; Hiltunen, Arto J

2016-06-01

The present study was carried out to examine the treatment effect of cognitive behavioral therapy provided by trainee therapists at a university clinic, focusing on health-related quality of life (HRQOL) optimism and symptoms. The study was conducted through a repeated measures design and included a treatment group (n = 21), which received cognitive behavioral therapy for an average of 10.7 therapy sessions and a control group (n = 14), that was put on a wait list for 8.6 weeks on average. After treatment, the treatment group improved significantly concerning general health (p = 0.028) and optimism (p = 0.027). In addition, clients improved in several areas within mental health and displayed some reduction in anxiety symptoms. Concurrently, the results also indicated some improvement within the control group, which may have been caused by the initial therapeutic contact, expectancy effects or spontaneous remission. The study concluded that cognitive behavioral therapy provided by trainee therapists may have a positive effect on areas within HRQOL and optimism. © 2016 Scandinavian Psychological Associations and John Wiley & Sons Ltd.

SU-E-T-590: Optimizing Magnetic Field Strengths with Matlab for An Ion-Optic System in Particle Therapy Consisting of Two Quadrupole Magnets for Subsequent Simulations with the Monte-Carlo Code FLUKA

DOE Office of Scientific and Technical Information (OSTI.GOV)

Baumann, K; Weber, U; Simeonov, Y

Purpose: Aim of this study was to optimize the magnetic field strengths of two quadrupole magnets in a particle therapy facility in order to obtain a beam quality suitable for spot beam scanning. Methods: The particle transport through an ion-optic system of a particle therapy facility consisting of the beam tube, two quadrupole magnets and a beam monitor system was calculated with the help of Matlab by using matrices that solve the equation of motion of a charged particle in a magnetic field and field-free region, respectively. The magnetic field strengths were optimized in order to obtain a circular andmore » thin beam spot at the iso-center of the therapy facility. These optimized field strengths were subsequently transferred to the Monte-Carlo code FLUKA and the transport of 80 MeV/u C12-ions through this ion-optic system was calculated by using a user-routine to implement magnetic fields. The fluence along the beam-axis and at the iso-center was evaluated. Results: The magnetic field strengths could be optimized by using Matlab and transferred to the Monte-Carlo code FLUKA. The implementation via a user-routine was successful. Analyzing the fluence-pattern along the beam-axis the characteristic focusing and de-focusing effects of the quadrupole magnets could be reproduced. Furthermore the beam spot at the iso-center was circular and significantly thinner compared to an unfocused beam. Conclusion: In this study a Matlab tool was developed to optimize magnetic field strengths for an ion-optic system consisting of two quadrupole magnets as part of a particle therapy facility. These magnetic field strengths could subsequently be transferred to and implemented in the Monte-Carlo code FLUKA to simulate the particle transport through this optimized ion-optic system.« less

Algorithms for the optimization of RBE-weighted dose in particle therapy.

PubMed

Horcicka, M; Meyer, C; Buschbacher, A; Durante, M; Krämer, M

2013-01-21

We report on various algorithms used for the nonlinear optimization of RBE-weighted dose in particle therapy. Concerning the dose calculation carbon ions are considered and biological effects are calculated by the Local Effect Model. Taking biological effects fully into account requires iterative methods to solve the optimization problem. We implemented several additional algorithms into GSI's treatment planning system TRiP98, like the BFGS-algorithm and the method of conjugated gradients, in order to investigate their computational performance. We modified textbook iteration procedures to improve the convergence speed. The performance of the algorithms is presented by convergence in terms of iterations and computation time. We found that the Fletcher-Reeves variant of the method of conjugated gradients is the algorithm with the best computational performance. With this algorithm we could speed up computation times by a factor of 4 compared to the method of steepest descent, which was used before. With our new methods it is possible to optimize complex treatment plans in a few minutes leading to good dose distributions. At the end we discuss future goals concerning dose optimization issues in particle therapy which might benefit from fast optimization solvers.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Heng, E-mail: hengli@mdanderson.org; Zhu, X. Ronald; Zhang, Xiaodong

Purpose: To develop and validate a novel delivery strategy for reducing the respiratory motion–induced dose uncertainty of spot-scanning proton therapy. Methods and Materials: The spot delivery sequence was optimized to reduce dose uncertainty. The effectiveness of the delivery sequence optimization was evaluated using measurements and patient simulation. One hundred ninety-one 2-dimensional measurements using different delivery sequences of a single-layer uniform pattern were obtained with a detector array on a 1-dimensional moving platform. Intensity modulated proton therapy plans were generated for 10 lung cancer patients, and dose uncertainties for different delivery sequences were evaluated by simulation. Results: Without delivery sequence optimization,more » the maximum absolute dose error can be up to 97.2% in a single measurement, whereas the optimized delivery sequence results in a maximum absolute dose error of ≤11.8%. In patient simulation, the optimized delivery sequence reduces the mean of fractional maximum absolute dose error compared with the regular delivery sequence by 3.3% to 10.6% (32.5-68.0% relative reduction) for different patients. Conclusions: Optimizing the delivery sequence can reduce dose uncertainty due to respiratory motion in spot-scanning proton therapy, assuming the 4-dimensional CT is a true representation of the patients' breathing patterns.« less

Algorithms for the optimization of RBE-weighted dose in particle therapy

NASA Astrophysics Data System (ADS)

Horcicka, M.; Meyer, C.; Buschbacher, A.; Durante, M.; Krämer, M.

2013-01-01

We report on various algorithms used for the nonlinear optimization of RBE-weighted dose in particle therapy. Concerning the dose calculation carbon ions are considered and biological effects are calculated by the Local Effect Model. Taking biological effects fully into account requires iterative methods to solve the optimization problem. We implemented several additional algorithms into GSI's treatment planning system TRiP98, like the BFGS-algorithm and the method of conjugated gradients, in order to investigate their computational performance. We modified textbook iteration procedures to improve the convergence speed. The performance of the algorithms is presented by convergence in terms of iterations and computation time. We found that the Fletcher-Reeves variant of the method of conjugated gradients is the algorithm with the best computational performance. With this algorithm we could speed up computation times by a factor of 4 compared to the method of steepest descent, which was used before. With our new methods it is possible to optimize complex treatment plans in a few minutes leading to good dose distributions. At the end we discuss future goals concerning dose optimization issues in particle therapy which might benefit from fast optimization solvers.

A Mathematical Tumor Model with Immune Resistance and Drug Therapy: An Optimal Control Approach

DOE PAGES

De Pillis, L. G.; Radunskaya, A.

2001-01-01

We present a competition model of cancer tumor growth that includes both the immune system response and drug therapy. This is a four-population model that includes tumor cells, host cells, immune cells, and drug interaction. We analyze the stability of the drug-free equilibria with respect to the immune response in order to look for target basins of attraction. One of our goals was to simulate qualitatively the asynchronous tumor-drug interaction known as “Jeffs phenomenon.” The model we develop is successful in generating this asynchronous response behavior. Our other goal was to identify treatment protocols that could improve standard pulsed chemotherapymore » regimens. Using optimal control theory with constraints and numerical simulations, we obtain new therapy protocols that we then compare with traditional pulsed periodic treatment. The optimal control generated therapies produce larger oscillations in the tumor population over time. However, by the end of the treatment period, total tumor size is smaller than that achieved through traditional pulsed therapy, and the normal cell population suffers nearly no oscillations.« less

A Mathematical Tumor Model with Immune Resistance and Drug Therapy: An Optimal Control Approach

DOE Office of Scientific and Technical Information (OSTI.GOV)

De Pillis, L. G.; Radunskaya, A.

We present a competition model of cancer tumor growth that includes both the immune system response and drug therapy. This is a four-population model that includes tumor cells, host cells, immune cells, and drug interaction. We analyze the stability of the drug-free equilibria with respect to the immune response in order to look for target basins of attraction. One of our goals was to simulate qualitatively the asynchronous tumor-drug interaction known as “Jeffs phenomenon.” The model we develop is successful in generating this asynchronous response behavior. Our other goal was to identify treatment protocols that could improve standard pulsed chemotherapymore » regimens. Using optimal control theory with constraints and numerical simulations, we obtain new therapy protocols that we then compare with traditional pulsed periodic treatment. The optimal control generated therapies produce larger oscillations in the tumor population over time. However, by the end of the treatment period, total tumor size is smaller than that achieved through traditional pulsed therapy, and the normal cell population suffers nearly no oscillations.« less

Economic benefits of optimizing anchor therapy for rheumatoid arthritis.

PubMed

Fautrel, Bruno

2012-06-01

The total cost of RA is substantial, particularly in patients with high levels of disability. There are considerable differences in cost between countries, driven in part by differences in the use of biologic therapies. Economic evaluations are needed to assess the extra cost of using these treatments and the benefits obtained, to ensure appropriate allocation of limited health care resources. The BeSt trial, evaluating four treatment strategies, found comparable medium-term efficacy but substantially higher costs with early biologic therapy. A systematic review of such cost-effectiveness analyses concluded that biologic therapy should be used after therapy has failed with less costly alternatives such as synthetic DMARDs and glucocorticoids. Optimizing such relatively low-cost therapy to improve outcomes may delay the need for biologic therapy, thereby saving costs. A simple model has confirmed the value of this approach. The addition of modified-release prednisone 5 mg/day to existing synthetic DMARD therapy in patients with active disease resulted in improvement in DAS-28 to below the threshold level for initiation of reimbursed biologic therapy in 28-34% of patients. On a conservative estimate (i.e. assuming no further benefits beyond the 12 weeks of the study and a 12-week wait-and-see approach to starting biologic therapy), cost savings amounted to nearly € 400 per patient. While treatment decisions should never be based only on cost considerations, prolonging disease control by optimizing the use of non-biologic treatments may bring benefits to patients and also economic benefits by delaying the need for biologic treatments.

A stochastic framework for spot-scanning particle therapy.

PubMed

Robini, Marc; Yuemin Zhu; Wanyu Liu; Magnin, Isabelle

2016-08-01

In spot-scanning particle therapy, inverse treatment planning is usually limited to finding the optimal beam fluences given the beam trajectories and energies. We address the much more challenging problem of jointly optimizing the beam fluences, trajectories and energies. For this purpose, we design a simulated annealing algorithm with an exploration mechanism that balances the conflicting demands of a small mixing time at high temperatures and a reasonable acceptance rate at low temperatures. Numerical experiments substantiate the relevance of our approach and open new horizons to spot-scanning particle therapy.

Mental health, fatigue and function are associated with increased risk of disease flare following TNF inhibitor tapering in patients with rheumatoid arthritis: an exploratory analysis of data from the Optimizing TNF Tapering in RA (OPTTIRA) trial

PubMed Central

Bechman, Katie; Sin, Fang En; Ibrahim, Fowzia; Norton, Sam; Matcham, Faith; Scott, David Lloyd; Cope, Andrew; Galloway, James

2018-01-01

Background Tapering of anti-tumour necrosis factor (TNF) therapy appears feasible, safe and effective in selected patients with rheumatoid arthritis (RA). Depression is highly prevalent in RA and may impact on flare incidence through various mechanisms. This study aims to investigate if psychological states predict flare in patients’ dose tapering their anti-TNF therapy. Methods This study is a post-hoc analysis of the Optimizing TNF Tapering in RA trial, a multicentre, randomised, open-label study investigating anti-TNF tapering in RA patients with sustained low disease activity. Patient-reported outcomes (Health Assessment Questionnaire, EuroQol 5-dimension scale, Functional Assessment of Chronic Illness Therapy fatigue scale (FACIT-F), 36-Item Short Form Survey (SF-36)) were collected at baseline. The primary outcome was flare, defined as an increase in 28-joint count Disease Activity Score (DAS28) ≥0.6 and ≥1 swollen joint. Discrete-time survival models were used to identify patient-reported outcomes that predict flare. Results Ninety-seven patients were randomised to taper their anti-TNF dose by either 33% or 66%. Forty-one patients flared. Higher baseline DAS28 score was associated with flare (adjusted HR 1.96 (95% CI 1.18 to 3.24), p=0.01). Disability (SF-36 physical component score), fatigue (FACIT-F) and mental health (SF-36 mental health subscale (MH)) predicted flare in unadjusted models. In multivariate analyses, only SF-36 MH remained a statistically significant predictor of flare (adjusted HR per 10 units 0.74 (95% CI 0.60 to 0.93), p=0.01). Conclusions Baseline DAS28 and mental health status are independently associated with flare in patients who taper their anti-TNF therapy. Fatigue and function also associate with flare but the effect disappears when adjusting for confounders. Given these findings, mental health and functional status should be considered in anti-TNF tapering decisions in order to optimise the likelihood of success. Trial registration numbers EudraCT Number: 2010-020738-24; ISRCTN: 28955701; Post-results. PMID:29862047

Audit and Feedback-Focused approach to Evidence-based Care in Treating patients with pneumonia in hospital (AFFECT Study)

PubMed Central

Halpape, Katelyn; Sulz, Linda; Schuster, Brenda; Taylor, Ron

2014-01-01

Background: Pneumonia is the eighth leading cause of death in Canada. Use of guideline-concordant therapy tempers the development of resistance, decreases health care costs, and reduces morbidity and mortality. Objectives: The purpose of this study was to optimize the treatment of patients with pneumonia under hospitalist care by focusing on best practice and local antibiogram data. The objectives were to collaborate with a hospitalist representative to optimize in-hospital treatment of patients with community-acquired, hospital-acquired, and health care–associated pneumonia; to complete a baseline audit to determine the proportion of antibiotic orders adhering to the strategy; to present the strategy and baseline audit findings to the hospitalists; to perform a post-intervention audit, with comparison to baseline, and to present results to the hospitalists; to expedite de-escalation to a narrower-spectrum antibiotic; to expedite parenteral-to-oral step-down therapy and promote appropriate duration of therapy; and to determine if a pneumonia scoring system was used. Methods: An audit and feedback intervention focusing on pre- and post-intervention retrospective chart audits was completed. Review of pneumonia guidelines and the local antibiogram assisted in identifying the study strategy. A presentation to the hospitalists outlined antimicrobial stewardship principles and described the findings of the baseline audit. Pre- and post-intervention audit results were compared. Results: Local best-practice treatment algorithms were developed for community-acquired pneumonia and for hospital-acquired and health care–associated pneumonia. The pre-intervention audit covered the period December 2011 to January 2012, with subsequent education and audit results presented to the hospitalists in November 2012. The post-intervention audit covered the period December 2012 to January 2013. Adherence to the treatment algorithms increased from 10% (2/21) in the pre-intervention audit to 38% (5/13) in the post-intervention audit. There was a trend to reduced duration of therapy in the post-intervention group. Conclusion: An audit and feedback intervention related to hospitalists’ prescribing for pneumonia increased adherence to local best practice. PMID:24634522

Delivery of optimized inpatient anticoagulation therapy: consensus statement from the anticoagulation forum.

PubMed

Nutescu, Edith A; Wittkowsky, Ann K; Burnett, Allison; Merli, Geno J; Ansell, Jack E; Garcia, David A

2013-05-01

To provide recommendations for optimized anticoagulant therapy in the inpatient setting and outline broad elements that need to be in place for effective management of anticoagulant therapy in hospitalized patients; the guidelines are designed to promote optimization of patient clinical outcomes while minimizing the risks for potential anticoagulation-related errors and adverse events. The medical literature was reviewed using MEDLINE (1946-January 2013), EMBASE (1980-January 2013), and PubMed (1947-January 2013) for topics and key words including, but not limited to, standards of practice, national guidelines, patient safety initiatives, and regulatory requirements pertaining to anticoagulant use in the inpatient setting. Non-English-language publications were excluded. Specific MeSH terms used include algorithms, anticoagulants/administration and dosage/adverse effects/therapeutic use, clinical protocols/standards, decision support systems, drug monitoring/methods, humans, inpatients, efficiency/ organizational, outcome and process assessment (health care), patient care team/organization and administration, program development/standards, quality improvement/organization and administration, thrombosis/ drug therapy, thrombosis/prevention and control, risk assessment/standards, patient safety/standards, and risk management/methods. Because of this document's scope, the medical literature was searched using a variety of strategies. When possible, recommendations are supported by available evidence; however, because this paper deals with processes and systems of care, high-quality evidence (eg, controlled trials) is unavailable. In these cases, recommendations represent the consensus opinion of all authors and are endorsed by the Board of Directors of the Anticoagulation Forum, an organization dedicated to optimizing anticoagulation care. The board is composed of physicians, pharmacists, and nurses with demonstrated expertise and experience in the management of patients receiving anticoagulation therapy. Recommendations for delivering optimized inpatient anticoagulation therapy were developed collaboratively by the authors and are summarized in 8 key areas: (1) process, (2) accountability, (3) integration, (4) standards of practice, (5) provider education and competency, (6) patient education, (7) care transitions, and (8) outcomes. Recommendations are intended to inform the development of coordinated care systems containing elements with demonstrated benefit in improvement of anticoagulation therapy outcomes. Recommendations for delivering optimized inpatient anticoagulation therapy are intended to apply to all clinicians involved in the care of hospitalized patients receiving anticoagulation therapy. Anticoagulants are high-risk medications associated with a significant rate of medication errors among hospitalized patients. Several national organizations have introduced initiatives to reduce the likelihood of patient harm associated with the use of anticoagulants. Health care organizations are under increasing pressure to develop systems to ensure the safe and effective use of anticoagulants in the inpatient setting. This document provides consensus guidelines for anticoagulant therapy in the inpatient setting and serves as a companion document to prior guidelines relevant for outpatients.

Play Therapy: Role in Reading Improvement.

ERIC Educational Resources Information Center

Carmichael, Karla

1991-01-01

Reviews the literature concerning the role of play therapy (particularly sandplay and nondirected play therapy) in the improvement of reading. Suggests that the role of play therapy is to support the child, encourage the child, and build self-esteem thus creating the optimal learning environment for reading improvement. (RS)

Assessment of hemodynamic load components affecting optimization of cardiac resynchronization therapy by lumped parameter mode.

PubMed

Xu, Ke; Butlin, Mark; Avolio, Alberto P

2012-01-01

Timing of biventricular pacing devices employed in cardiac resynchronization therapy (CRT) is a critical determinant of efficacy of the procedure. Optimization is done by maximizing function in terms of arterial pressure (BP) or cardiac output (CO). However, BP and CO are also determined by the hemodynamic load of the pulmonary and systemic vasculature. This study aims to use a lumped parameter circulatory model to assess the influence of the arterial load on the atrio-ventricular (AV) and inter-ventricular (VV) delay for optimal CRT performance.

A Comparison of Aphasia Therapy Outcomes before and after a Very Early Rehabilitation Programme Following Stroke

ERIC Educational Resources Information Center

Godecke, Erin; Ciccone, Natalie A.; Granger, Andrew S.; Rai, Tapan; West, Deborah; Cream, Angela; Cartwright, Jade; Hankey, Graeme J.

2014-01-01

Background: Very early aphasia rehabilitation studies have shown mixed results. Differences in therapy intensity and therapy type contribute significantly to the equivocal results. Aims: To compare a standardized, prescribed very early aphasia therapy regimen with a historical usual care control group at therapy completion (4-5 weeks post-stroke)…

Aspergillus Osteomyelitis: Epidemiology, Clinical Manifestations, Management, and Outcome

PubMed Central

Gamaletsou, Maria N.; Rammaert, Blandine; Bueno, Marimelle A.; Moriyama, Brad; Sipsas, Nikolaos V.; Kontoyiannis, Dimitrios P.; Roilides, Emmanuel; Zeller, Valerie; Prinapori, Roberta; Tajaldeen, Saad Jaber; Brause, Barry; Lortholary, Olivier; Walsh, Thomas J.

2014-01-01

Background The epidemiology, pathogenesis, diagnosis, and management of Aspergillus osteomyelitis are not well understood. Methods Protocol-defined cases of Aspergillus osteomyelitis published in the English literature were reviewed for comorbidities, microbiology, mechanisms of infection, clinical manifestations, radiological findings, inflammatory biomarkers, antifungal therapy, and outcome. Results Among 180 evaluable patients, 127 (71%) were males. Possible predisposing medical conditions in 103 (57%) included pharmacological immunosuppression, primary immunodeficiency, and neutropenia. Seventy-three others (41%) had prior open fracture, trauma or surgery. Eighty (44%) followed a hematogenous mechanism, 58 (32%) contiguous infections, and 42 (23%) direct inoculation. Aspergillus osteomyelitis was the first manifestation of aspergillosis in 77%. Pain and tenderness were present in 80%. The most frequently infected sites were vertebrae (46%), cranium (23%), ribs (16%), and long bones (13%). Patients with vertebral Aspergillus osteomyelitis had more previous orthopedic surgery (19% vs 0%; P=0.02), while those with cranial osteomyelitis had more diabetes mellitus (32% vs 8%; P=0.002) and prior head/neck surgery (12% vs 0%; P=0.02). Radiologic findings included osteolysis, soft-tissue extension, and uptake on T2-weighted images. Vertebral body Aspergillus osteomyelitis was complicated by spinal-cord compression in 47% and neurological deficits in 41%. Forty-four patients (24%) received only antifungal therapy, while 121(67%) were managed with surgery and antifungal therapy. Overall mortality was 25%. Median duration of therapy was 90 days (range, 10–772 days). There were fewer relapses in patients managed with surgery plus antifungal therapy in comparison to those managed with antifungal therapy alone (8% vs 30%; P=0.006). Conclusions Aspergillus osteomyelitis is a debilitating infection affecting both immunocompromised and immunocompetent patients. The most common sites are vertebrae, ribs, and cranium. Based upon this comprehensive review, management of Aspergillus osteomyelitis optimally includes antifungal therapy and selective surgery to avoid relapse and to achieve a complete response. PMID:24378282

Oncolytic Sendai Virus Therapy of Canine Mast Cell Tumors (A Pilot Study).

PubMed

Ilyinskaya, Galina V; Mukhina, Elena V; Soboleva, Alesya V; Matveeva, Olga V; Chumakov, Peter M

2018-01-01

Background: Canine mastocytomas (mast cell tumors) represent a common malignancy among many dog breeds. A typical treatment strategy for canine mastocytomas includes surgery, chemo- and radio-therapy, although in many cases the therapy fails and the disease progression resumes. New treatment approaches are needed. Aims: The goal of this pilot study was to examine safety and efficacy of oncolytic Sendai virus therapy administered to canine patients with cutaneous or subcutaneous mastocytomas. Materials and Methods: Six canine patients, with variable grades and stages of the disease, received virus therapy, either as a monotherapy, or in combination with surgery. The therapy included two or more virus applications administered weekly or biweekly. Each application of Sendai virus (10 7 -10 8.6 EID50) consisted of multiple individual 0.01-0.1 ml injections delivered intratumorally, intradermally around a tumor, and under a tumor bed. Results: The treatment was well tolerated, with minor transitory side effects. Of the six dogs, two did not receive surgery or any other treatment besides the virus injections. The other four animals underwent radical or debulking surgeries, and in three of them the subsequent administration of Sendai virus completely cleared locally recurrent or/and remaining tumor masses. Five dogs demonstrated a complete response to the treatment, the animals remained disease free during the time of observation (2-3 years). One dog responded only partially to the virotherapy; its after-surgical recurrent tumor and some, but not all, metastases were cleared. This dog had the most advanced stage of the disease with multiple enlarged lymph nodes and cutaneous metastases. Conclusion: The results of the pilot study suggest that Sendai virus injections could be safe and efficient for the treatment of dogs affected by mastocytomas.They also suggest the need of further studies for finding optimal schemes and schedules for this kind of therapy.

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

PubMed

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

2015-01-01

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

Reinforcement Learning Strategies for Clinical Trials in Non-small Cell Lung Cancer

PubMed Central

Zhao, Yufan; Zeng, Donglin; Socinski, Mark A.; Kosorok, Michael R.

2010-01-01

Summary Typical regimens for advanced metastatic stage IIIB/IV non-small cell lung cancer (NSCLC) consist of multiple lines of treatment. We present an adaptive reinforcement learning approach to discover optimal individualized treatment regimens from a specially designed clinical trial (a “clinical reinforcement trial”) of an experimental treatment for patients with advanced NSCLC who have not been treated previously with systemic therapy. In addition to the complexity of the problem of selecting optimal compounds for first and second-line treatments based on prognostic factors, another primary goal is to determine the optimal time to initiate second-line therapy, either immediately or delayed after induction therapy, yielding the longest overall survival time. A reinforcement learning method called Q-learning is utilized which involves learning an optimal regimen from patient data generated from the clinical reinforcement trial. Approximating the Q-function with time-indexed parameters can be achieved by using a modification of support vector regression which can utilize censored data. Within this framework, a simulation study shows that the procedure can extract optimal regimens for two lines of treatment directly from clinical data without prior knowledge of the treatment effect mechanism. In addition, we demonstrate that the design reliably selects the best initial time for second-line therapy while taking into account the heterogeneity of NSCLC across patients. PMID:21385164

Concomitant herpes simplex virus colitis and hepatitis in a man with ulcerative colitis

PubMed Central

Phadke, Varun K.; Friedman-Moraco, Rachel J.; Quigley, Brian C.; Farris, Alton B.; Norvell, J. P.

2016-01-01

Abstract Background: Herpesvirus infections often complicate the clinical course of patients with inflammatory bowel disease; however, invasive disease due to herpes simplex virus is distinctly uncommon. Methods: We present a case of herpes simplex virus colitis and hepatitis, review all the previously published cases of herpes simplex virus colitis, and discuss common clinical features and outcomes. We also discuss the epidemiology, clinical manifestations, diagnosis, and management of herpes simplex virus infections, focusing specifically on patients with inflammatory bowel disease. Results: A 43-year-old man with ulcerative colitis, previously controlled with an oral 5-aminosalicylic agent, developed symptoms of a colitis flare that did not respond to treatment with systemic corticosteroid therapy. One week later he developed orolabial ulcers and progressive hepatic dysfunction, with markedly elevated transaminases and coagulopathy. He underwent emergent total colectomy when imaging suggested bowel micro-perforation. Pathology from both the colon and liver was consistent with herpes simplex virus infection, and a viral culture of his orolabial lesions and a serum polymerase chain reaction assay also identified herpes simplex virus. He was treated with systemic antiviral therapy and made a complete recovery. Conclusions: Disseminated herpes simplex virus infection with concomitant involvement of the colon and liver has been reported only 3 times in the published literature, and to our knowledge this is the first such case in a patient with inflammatory bowel disease. The risk of invasive herpes simplex virus infections increases with some, but not all immunomodulatory therapies. Optimal management of herpes simplex virus in patients with inflammatory bowel disease includes targeted prophylactic therapy for patients with evidence of latent infection, and timely initiation of antiviral therapy for those patients suspected to have invasive disease. PMID:27759636

Vasopressor Use for Severe Hypotension—A Multicentre Prospective Observational Study

PubMed Central

Cook, Deborah J.; Meade, Maureen O.; Seely, Andrew; Day, Andrew G.; Charbonney, Emmanuel; Serri, Karim; Skrobik, Yoanna; Hebert, Paul; St-Arnaud, Charles; Quiroz-Martinez, Hector; Mayette, Michaël; Heyland, Daren K.

2017-01-01

Background The optimal approach to titrate vasopressor therapy is unclear. Recent sepsis guidelines recommend a mean arterial pressure (MAP) target of 65 mmHg and higher for chronic hypertensive patients. As data emerge from clinical trials comparing blood pressure targets for vasopressor therapy, an accurate description of usual care is required to interpret study results. Our aim was to measure MAP values during vasopressor therapy in Canadian intensive care units (ICUs) and to compare these with stated practices and guidelines. Method In a multicenter prospective cohort study of critically ill adults with severe hypotension, we recorded MAP and vasopressor doses hourly. We investigated variability across patients and centres using multivariable regression models and Analysis of variance (ANOVA), respectively. Results We included data from 56 patients treated in 6 centers. The mean (standard deviation [SD]) age and Acute Physiology and Chronic Health Evaluation (APACHE) II score were 64 (14) and 25 (8). Half (28 of 56) of the patients were at least 65 years old, and half had chronic hypertension. The patient-averaged MAP while receiving vasopressors was 75 mm Hg (6) and the median (1st quartile, 3rd quartile) duration of vasopressor therapy was 43 hours (23, 84). MAP achieved was not associated with history of underlying hypertension (p = 0.46) but did vary by center (p<0.001). Conclusions In this multicenter, prospective observational study, the patient-level average MAP while receiving vasopressors for severe hypotension was 75 mmHg, approximately 10 mmHg above current recommendations and stated practices. Moreover, our results do not support the notion that clinicians tailor vasopressor therapy to individual patient characteristics such as underlying chronic hypertension but MAP achieved while receiving vasopressors varied by site. PMID:28107357

Effectiveness of intense, activity-based physical therapy for individuals with spinal cord injury in promoting motor and sensory recovery: Is olfactory mucosa autograft a factor?

PubMed Central

Larson, Cathy A.; Dension, Paula M.

2013-01-01

Background/objectives Rehabilitation for individuals with spinal cord injury (SCI) is expanding to include intense, activity-based, out-patient physical therapy (PT). The study's primary purposes were to (i) examine the effectiveness of intense PT in promoting motor and sensory recovery in individuals with SCI and (ii) compare recovery for individuals who had an olfactory mucosa autograft (OMA) with individuals who did not have the OMA while both groups participated in the intense PT program. Methods Prospective, non-randomized, non-blinded, intervention study. Using the American Spinal Injury Association examination, motor and sensory scores for 23 (7 OMA, 6 matched control and 10 other) participants were recorded. Results Mean therapy dosage was 137.3 total hours. The participants’ total, upper and lower extremity motor scores improved significantly while sensory scores did not improve during the first 60 days and from initial to discharge examination. Incomplete SCI or paraplegia was associated with greater motor recovery. Five of 14 participants converted from motor-complete to motor-incomplete SCI. Individuals who had the OMA and participated in intense PT did not have greater sensory or greater magnitude or rate of motor recovery as compared with participants who had intense PT alone. Conclusion This study provides encouraging evidence as to the effectiveness of intense PT for individuals with SCI. Future research is needed to identify the optimal therapy dosage and specific therapeutic activities required to generate clinically meaningful recovery for individuals with SCI including those who elect to undergo a neural recovery/regenerative surgical procedure and those that elect intense therapy alone. PMID:23433335

Optimizing signal recycling for detecting a stochastic gravitational-wave background

NASA Astrophysics Data System (ADS)

Tao, Duo; Christensen, Nelson

2018-06-01

Signal recycling is applied in laser interferometers such as the Advanced Laser Interferometer Gravitational-Wave Observatory (aLIGO) to increase their sensitivity to gravitational waves. In this study, signal recycling configurations for detecting a stochastic gravitational wave background are optimized based on aLIGO parameters. Optimal transmission of the signal recycling mirror (SRM) and detuning phase of the signal recycling cavity under a fixed laser power and low-frequency cutoff are calculated. Based on the optimal configurations, the compatibility with a binary neutron star (BNS) search is discussed. Then, different laser powers and low-frequency cutoffs are considered. Two models for the dimensionless energy density of gravitational waves , the flat model and the model, are studied. For a stochastic background search, it is found that an interferometer using signal recycling has a better sensitivity than an interferometer not using it. The optimal stochastic search configurations are typically found when both the SRM transmission and the signal recycling detuning phase are low. In this region, the BNS range mostly lies between 160 and 180 Mpc. When a lower laser power is used the optimal signal recycling detuning phase increases, the optimal SRM transmission increases and the optimal sensitivity improves. A reduced low-frequency cutoff gives a better sensitivity limit. For both models of , a typical optimal sensitivity limit on the order of 10‑10 is achieved at a reference frequency of Hz.

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

PubMed Central

2012-01-01

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 effort towards formulating, optimizing and scaling up PLGA-CURC by using Solid-Oil/Water emulsion technique was demonstrated. The process used CCD-RSM for optimization and further scaled up to produce 5 g of PLGA-CURC with almost similar physicochemical characteristics as that of the primary formulated batch. PMID:22937885

Carotid stenosis - basing treatment on individual patients' needs. Optimal medical therapy alone or accompanied by stenting or endarterectomy.

PubMed

Langhoff, Ralf

2018-01-01

Though carotid artery stenosis is a known origin of stroke, risk assessment and treatment modality are not yet satisfactorily established. Guideline updates according to latest evidence are expected shortly. Current clinical weakness concerns in particular the identification of "at-risk" patients. Beside the symptomatic status and the degree of stenosis, further signs of unstable plaque on carotid and cerebral imaging should be considered. Moreover, medical and endovascular therapy are continuously improving. Randomized trials and meta-analyses have shown similar long-term results for protected carotid artery stenting and endarterectomy. However, endovascular revascularization was associated with an increased 30-day rate of minor strokes. Newly developed embolic protection devices could possibly compensate for this disadvantage. Furthermore, high-level optimal medical therapy alone is currently being evaluated comparatively. We assume that a comprehensive evaluation of plaque vulnerability, serious consideration of advanced embolic protection, and more space for optimal medical therapy alone according to latest evidence, will benefit patients with carotid stenosis.

14 day sequential therapy versus 10 day bismuth quadruple therapy containing high-dose esomeprazole in the first-line and second-line treatment of Helicobacter pylori: a multicentre, non-inferiority, randomized trial.

PubMed

Liou, Jyh-Ming; Chen, Chieh-Chang; Fang, Yu-Jen; Chen, Po-Yueh; Chang, Chi-Yang; Chou, Chu-Kuang; Chen, Mei-Jyh; Tseng, Cheng-Hao; Lee, Ji-Yuh; Yang, Tsung-Hua; Chiu, Min-Chin; Yu, Jian-Jyun; Kuo, Chia-Chi; Luo, Jiing-Chyuan; Hsu, Wen-Feng; Hu, Wen-Hao; Tsai, Min-Horn; Lin, Jaw-Town; Shun, Chia-Tung; Twu, Gary; Lee, Yi-Chia; Bair, Ming-Jong; Wu, Ming-Shiang

2018-05-29

Whether extending the treatment length and the use of high-dose esomeprazole may optimize the efficacy of Helicobacter pylori eradication remains unknown. To compare the efficacy and tolerability of optimized 14 day sequential therapy and 10 day bismuth quadruple therapy containing high-dose esomeprazole in first-line therapy. We recruited 620 adult patients (≥20 years of age) with H. pylori infection naive to treatment in this multicentre, open-label, randomized trial. Patients were randomly assigned to receive 14 day sequential therapy or 10 day bismuth quadruple therapy, both containing esomeprazole 40 mg twice daily. Those who failed after 14 day sequential therapy received rescue therapy with 10 day bismuth quadruple therapy and vice versa. Our primary outcome was the eradication rate in the first-line therapy. Antibiotic susceptibility was determined. ClinicalTrials.gov: NCT03156855. The eradication rates of 14 day sequential therapy and 10 day bismuth quadruple therapy were 91.3% (283 of 310, 95% CI 87.4%-94.1%) and 91.6% (284 of 310, 95% CI 87.8%-94.3%) in the ITT analysis, respectively (difference -0.3%, 95% CI -4.7% to 4.4%, P = 0.886). However, the frequencies of adverse effects were significantly higher in patients treated with 10 day bismuth quadruple therapy than those treated with 14 day sequential therapy (74.4% versus 36.7% P < 0.0001). The eradication rate of 14 day sequential therapy in strains with and without 23S ribosomal RNA mutation was 80% (24 of 30) and 99% (193 of 195), respectively (P < 0.0001). Optimized 14 day sequential therapy was non-inferior to, but better tolerated than 10 day bismuth quadruple therapy and both may be used in first-line treatment in populations with low to intermediate clarithromycin resistance.

Spectral anomaly methods for aerial detection using KUT nuisance rejection

NASA Astrophysics Data System (ADS)

Detwiler, R. S.; Pfund, D. M.; Myjak, M. J.; Kulisek, J. A.; Seifert, C. E.

2015-06-01

This work discusses the application and optimization of a spectral anomaly method for the real-time detection of gamma radiation sources from an aerial helicopter platform. Aerial detection presents several key challenges over ground-based detection. For one, larger and more rapid background fluctuations are typical due to higher speeds, larger field of view, and geographically induced background changes. As well, the possible large altitude or stand-off distance variations cause significant steps in background count rate as well as spectral changes due to increased gamma-ray scatter with detection at higher altitudes. The work here details the adaptation and optimization of the PNNL-developed algorithm Nuisance-Rejecting Spectral Comparison Ratios for Anomaly Detection (NSCRAD), a spectral anomaly method previously developed for ground-based applications, for an aerial platform. The algorithm has been optimized for two multi-detector systems; a NaI(Tl)-detector-based system and a CsI detector array. The optimization here details the adaptation of the spectral windows for a particular set of target sources to aerial detection and the tailoring for the specific detectors. As well, the methodology and results for background rejection methods optimized for the aerial gamma-ray detection using Potassium, Uranium and Thorium (KUT) nuisance rejection are shown. Results indicate that use of a realistic KUT nuisance rejection may eliminate metric rises due to background magnitude and spectral steps encountered in aerial detection due to altitude changes and geographically induced steps such as at land-water interfaces.

The role of repeating optimization of atrioventricular interval during interim and long-term follow-up after cardiac resynchronization therapy.

PubMed

Zhang, Qing; Fung, Jeffrey Wing-Hong; Chan, Yat-Sun; Chan, Hamish Chi-Kin; Lin, Hong; Chan, Skiva; Yu, Cheuk-Man

2008-02-29

Cardiac resynchronization therapy (CRT) is an effective therapy for heart failure patients with electromechanical delay. Optimization of atrioventricular interval (AVI) is a cardinal component for the benefits. However, it is unknown if the AVI needs to be re-optimized during long-term follow-up. Thirty-one patients (66+/-11 years, 20 males) with sinus rhythm who received CRT underwent serial optimization of AVI at day 1, 3-month and during long-term follow-up by pulse Doppler echocardiography (PDE). At long-term follow-up, the optimal AVI and cardiac output (CO) estimated by non-invasive impedance cardiography (ICG) were compared with those by PDE. The follow-up was 16+/-11 months. There was no significant difference in the mean optimal AVI when compared between any 2 time points among day 1 (99+/-30 ms), 3-month (97+/-28 ms) and long-term follow-up (94+/-28 ms). However, in individual patient, the optimal AVI remained unchanged only in 14 patients (44%), and was shortened in 12 (38%) and lengthened in 6 patients (18%). During long-term follow-up, although the mean optimal AVIs obtained by PDE or ICG (94+/-28 vs. 92+/-29 ms) were not different, a discrepancy was found in 14 patients (45%). For the same AVI, the CO measured by ICG was systematically higher than that by PDE (3.5+/-0.8 Vs. 2.7+/-0.6 L/min, p<0.001). Optimization of AVI after CRT appears necessary during follow-up as it was readjusted in 55% of patients. Although AVI optimization by ICG was feasible, further studies are needed to confirm its role in optimizing AVI after CRT.

Rectal artemisinins for malaria: a review of efficacy and safety from individual patient data in clinical studies

PubMed Central

Gomes, Melba; Ribeiro, Isabela; Warsame, Marian; Karunajeewa, Harin; Petzold, Max

2008-01-01

Background Rectal administration of artemisinin derivatives has potential for early treatment for severe malaria in remote settings where injectable antimalarial therapy may not be feasible. Preparations available include artesunate, artemisinin, artemether and dihydroartemisinin. However each may have different pharmacokinetic properties and more information is needed to determine optimal dose and comparative efficacy with each another and with conventional parenteral treatments for severe malaria. Methods Individual patient data from 1167 patients in 15 clinical trials of rectal artemisinin derivative therapy (artesunate, artemisinin and artemether) were pooled in order to compare the rapidity of clearance of Plasmodium falciparum parasitaemia and the incidence of reported adverse events with each treatment. Data from patients who received comparator treatment (parenteral artemisinin derivative or quinine) were also included. Primary endpoints included percentage reductions in parasitaemia at 12 and 24 hours. A parasite reduction of >90% at 24 hours was defined as parasitological success. Results Artemisinin and artesunate treatment cleared parasites more rapidly than parenteral quinine during the first 24 hours of treatment. A single higher dose of rectal artesunate treatment was five times more likely to achieve >90% parasite reductions at 24 hours than were multiple lower doses of rectal artesunate, or a single lower dose administration of rectal artemether. Conclusion Artemisinin and artesunate suppositories rapidly eliminate parasites and appear to be safe. There are less data on artemether and dihydroartemisinin suppositories. The more rapid parasite clearance of single high-dose regimens suggests that achieving immediate high drug concentrations may be the optimal strategy. PMID:18373841

Design and Parameter Study of Integrated Microfluidic Platform for CTC Isolation and Enquiry; A Numerical Approach.

PubMed

Shamloo, Amir; Ahmad, Saba; Momeni, Maede

2018-06-18

Being the second cause of mortality across the globe, there is now a persistent effort to establish new cancer medication and therapies. Any accomplishment in treating cancers entails the existence of accurate identification systems empowering the early diagnosis. Recent studies indicate CTCs’ potential in cancer prognosis as well as therapy monitoring. The chief shortcoming with CTCs is that they are exceedingly rare cells in their clinically relevant concentration. Here, we simulated a microfluidic construct devised for immunomagnetic separation of the particles of interest from the background cells. This separation unit is integrated with a mixer subunit. The mixer is envisioned for mixing the CTC enriched stream with lysis buffer to extract the biological material of the cell. Some modification was proposed on mixing geometry improving the efficacy of the functional unit. A valuation of engaged forces was made and some forces were neglected due to their order of magnitude. The position of the magnet was also optimized by doing parametric study. For the mixer unit, the effect of applied voltage and frequency on mixing index was studied to find the optimal voltage and frequency which provides better mixing. Above-mentioned studies were done on isolated units and the effect of each functional unit on the other is not studied. As the final step, an integrated microfluidic platform composed of both functional subunits was simulated simultaneously. To ensure the independence of results from the grid, grid studies were also performed. The studies carried out on the construct reveal its potential for diagnostic application.

A cost-utility analysis of ablative therapy for Barrett’s esophagus

PubMed Central

Inadomi, John M.; Somsouk, Ma; Madanick, Ryan D.; Thomas, Jennifer P.; Shaheen, Nicholas J.

2009-01-01

Background & Aims Recommendations for patients with Barrett’s esophagus (BE) include endoscopic surveillance with esophagectomy for early-stage cancer, although new technologies to ablate dysplasia and metaplasia are available. This study compares the cost-utility of ablation with that of endoscopic surveillance strategies. Methods A decision analysis model was created to examine a population of patients with BE (mean age 50), with separate analyses for patients with no dysplasia, low-grade dysplasia (LGD), or high-grade dysplasia (HGD). Strategies compared were: no endoscopic surveillance; endoscopic surveillance with ablation for incident dysplasia; immediate ablation followed by endoscopic surveillance in all patients or limited to patients in whom metaplasia persisted, and esophagectomy. Ablation modalities modeled included radiofrequency, argon plasma coagulation, multipolar electrocoagulation and photodynamic therapy. Results Endoscopic ablation for patients with HGD could increase life expectancy by 3 quality-adjusted years at an incremental cost of < $6,000, compared with no intervention. Patients with LGD or no dysplasia can also be optimally managed with ablation, but continued surveillance after eradication of metaplasia is expensive. If ablation permanently eradicates at least 28% of LGD or 40% of non-dysplastic metaplasias, ablation would be preferred to surveillance. Conclusions Endoscopic ablation could be the preferred strategy for managing patients with BE with HGD. Ablation might also be preferred in subjects with LGD or no dysplasia, but the cost-effectiveness depends on the long-term effectiveness of ablation and whether surveillance endoscopy can be discontinued following successful ablation. As further post-ablation data become available, the optimal management strategy will be clarified. PMID:19272389

Response to Nadler's Commentary on Arch and Craske's (2011) "Addressing Relapse in Cognitive Behavioral Therapy for Panic Disorder: Methods for Optimizing Long-Term Treatment Outcomes"

ERIC Educational Resources Information Center

Arch, Joanna J.; Craske, Michelle G.

2012-01-01

Nadler (this issue), in his commentary of our article, "Addressing Relapse in Cognitive Behavioral Therapy for Panic Disorder: Methods for Optimizing Long-Term Treatment Outcomes" (Arch & Craske, 2011), argues that we misrepresent the role of panic attacks within learning theory and overlook cognitive treatment targets. He presents several case…

SU-F-T-178: Optimized Design of a Diamond Detector Specifically Dedicated to the Dose Distribution Measurements in Clinical Proton Pencil Beams

DOE Office of Scientific and Technical Information (OSTI.GOV)

Moignier, C; Pomorski, M; Agelou, M

2016-06-15

Purpose: In proton-therapy, pencil beam scanning (PBS) dosimetry presents a real challenge due to the small size of the beam (about 3 to 8 mm in FWHM), the pulsed high dose rate (up to 100 Gy/s) and the proton energy variation (about 30 MeV to 250 MeV). In the framework of French INSERM DEDIPRO project, a specifically dedicated single crystal diamond dosimeter (SCDDo) was developed with the objective of obtaining accurate measurements of the dose distribution in PBS modality. Methods: Monte Carlo simulations with MCNPX were performed. A small proton beam of 5 mm in FWHM was simulated as wellmore » as diamond devices with various size, thickness and holder composition. The calculated doses-to-diamond were compared with the doses-to-water in order to reduce the perturbation effects. Monte-Carlo simulations lead to an optimized SCDDo design for small proton beams dosimetry. Following the optimized design, SCDDos were mounted in water-equivalent holders with electrical connection adapted to standard electrometer. First, SCDDos performances (stability, repeatability, signal-to-background ratio…) were evaluated with conventional photon beams. Then, characterizations (dose linearity, dose rate dependence…) with wide proton beams were performed at proton-therapy center (IC-CPO) from Curie Institute (France) with the passive proton delivery technique, in order to confirm dosimetric requirements. Finally, depth-dose distributions were measured in a water tank, for native and modulated Bragg Peaks with the collimator of 12 cm, and compared to a commercial PPC05 parallel-plate ionization chamber reference detector. Lateral-dose profiles were also measured with the collimator of 5 mm, and compared to a commercial SFD diode. Results: The results show that SCDDo design does not disturb the dose distributions. Conclusion: The experimental dose distributions with the SCDDo are in good agreement with the commercial detectors and no energy dependence was observed with this device configuration.« less

Adherence to antiretroviral therapy and treatment outcomes among conflict-affected and forcibly displaced populations: a systematic review

PubMed Central

2012-01-01

Background Optimal adherence to highly active antiretroviral therapy (HAART) is required to promote viral suppression and to prevent disease progression and mortality. Forcibly displaced and conflict-affected populations may face challenges succeeding on HAART. We performed a systematic review of the literature on adherence to HAART and treatment outcomes in these groups, including refugees and internally-displaced persons (IDPs), assessed the quality of the evidence and suggest a future research program. Methods Medline, Embase, and Global Health databases for 1995–2011 were searched using the Ovid platform. A backward citation review of subsequent work that had cited the Ovid results was performed using the Web of Science database. ReliefWeb and Médecins Sans Frontières (MSF) websites were searched for additional grey literature. Results and conclusion We screened 297 records and identified 17 reports covering 15 quantitative and two qualitative studies from 13 countries. Three-quarters (11/15) of the quantitative studies were retrospective studies based on chart review; five studies included <100 clients. Adherence or treatment outcomes were reported in resettled refugees, conflict-affected persons, internally-displaced persons (IDPs), and combinations of refugees, IDPs and other foreign-born persons. The reviewed reports showed promise for conflict-affected and forcibly-displaced populations; the range of optimal adherence prevalence reported was 87–99.5%. Treatment outcomes, measured using virological, immunological and mortality estimates, were good in relation to non-affected groups. Given the diversity of settings where forcibly-displaced and conflict-affected persons access ART, further studies on adherence and treatment outcomes are needed to support scale-up and provide evidence-based justifications for inclusion of these vulnerable groups in national treatment plans. Future studies and program evaluations should focus on systematic monitoring of adherence and treatment interruptions by using facility-based pharmacy records, understanding threats to optimal adherence and timely linkage to care throughout the displacement cycle, and testing interventions designed to support adherence and treatment outcomes in these settings. PMID:23110782

LD-Aminopterin in the Canine Homologue of Human Atopic Dermatitis: A Randomized, Controlled Trial Reveals Dosing Factors Affecting Optimal Therapy

PubMed Central

Zebala, John A.; Mundell, Alan; Messinger, Linda; Griffin, Craig E.; Schuler, Aaron D.; Kahn, Stuart J.

2014-01-01

Background Options are limited for patients with atopic dermatitis (AD) who do not respond to topical treatments. Antifolate therapy with systemic methotrexate improves the disease, but is associated with adverse effects. The investigational antifolate LD-aminopterin may offer improved safety. It is not known how antifolate dose and dosing frequency affect efficacy in AD, but a primary mechanism is thought to involve the antifolate-mediated accumulation of 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR). However, recent in vitro studies indicate that AICAR increases then decreases as a function of antifolate concentration. To address this issue and understand how dosing affects antifolate efficacy in AD, we examined the efficacy and safety of different oral doses and schedules of LD-aminopterin in the canine model of AD. Methods and Findings This was a multi-center, double-blind trial involving 75 subjects with canine AD randomized to receive up to 12 weeks of placebo, once-weekly (0.007, 0.014, 0.021 mg/kg) or twice-weekly (0.007 mg/kg) LD-aminopterin. The primary efficacy outcome was the Global Score (GS), a composite of validated measures of disease severity and itch. GS improved in all once-weekly cohorts, with 0.014 mg/kg being optimal and significant (43%, P<0.01). The majority of improvement was seen by 8 weeks. In contrast, GS in the twice-weekly cohort was similar to placebo and worse than all once-weekly cohorts. Adverse events were similar across all treated cohorts and placebo. Conclusions Once-weekly LD-aminopterin was safe and efficacious in canine AD. Twice-weekly dosing negated efficacy despite having the same daily and weekly dose as effective once-weekly regimens. Optimal dosing in this homologue of human AD correlated with the concentration-selective accumulation of AICAR in vitro, consistent with AICAR mediating LD-aminopterin efficacy in AD. PMID:25255447

Comparison of Pain Thresholds and Analgesic Effects of Parecoxib Sodium in Surgical Patients of Different Racial and Religious Backgrounds.

PubMed

Li, Li-Biao; Hu, Yu; Liu, Chao; Gu, Miao-Ning

2015-06-01

To explore the differences of the thresholds of pain and analgesic effects of parecoxib sodium among patients with different racial and religious backgrounds. A total of 48 male patients aged 18 to 38 years who had undergone elective laparoscopic appendectomy under general anesthesia in our centers were enrolled in our study and then divided into 6 groups(n=8 in each group)based on their racial backgrounds(three levels:Mongoloid,Negroid,and Europoid)and religious backgrounds(two levels:without religion background,with religion background).All subjects received the same anesthesia,surgical procedure,and postoperative analgesia with parecoxib sodium. The temperature pain threshold and electrical pain threshold were detected 1h before and after analgesia. The threshold of pain was higher in Europoids than in Negroids and Mongoloids before and after treatment. The temperature pain threshold and electrical pain threshold were not significantly different between subjects with or without religious background(before analgesic therapy:F=251.119,P=0.130,F=275.861,P=0.059;after analgesic therapy:F=308.531,P=0.086,F=180.062,P=0.078). Also,there was no interaction between the racial and religious backgrous in terms of temperature pain threshold and electrical pain threshold(F=13.553,P=0.091,F=22.001,P= 0.089;after analgesic therapy:F=4.624,P=0.089,F=15.935,P=0.094). The threshold of pain differs among individuals with different racial background:it is highest in Europoids,followed by Negroids and Mongoloids. It shows no obvious difference in people with different religious backgrounds.

Application of the cognitive therapy model to initial crisis assessment.

PubMed

Calvert, Patricia; Palmer, Christine

2003-03-01

This article provides a background to the development of cognitive therapy and cognitive therapeutic skills with a specific focus on the treatment of a depressive episode. It discusses the utility of cognitive therapeutic strategies to the model of crisis theory and initial crisis assessment currently used by the Community Assessment & Treatment Team of Waitemata District Health Board on the North Shore of Auckland, New Zealand. A brief background to cognitive therapy is provided, followed by a comprehensive example of the use of the Socratic questioning method in guiding collaborative assessment and treatment of suicidality by nurses during the initial crisis assessment.

Vulnerability and Protection Talk: Systemic Therapy Process with People with Intellectual Disability

ERIC Educational Resources Information Center

Pote, Helen; Mazon, Teresa; Clegg, Jennifer; King, Susan

2011-01-01

Background: Vulnerability and protection are key concepts within the literature relating to systemic therapy for people with an intellectual disability (ID). This paper explores the processes by which these concepts were discussed in systemic therapy sessions. Method: Four videotapes of systemic therapy sessions were evaluated using a qualitative…

Reinventing Family Therapy: Teaching Family Intervention as a New Treatment Modality

ERIC Educational Resources Information Center

Josephson, Allan M.

2008-01-01

Objective: This article discusses the pedagogy of teaching family therapy in the new millennium. It draws on the strengths of "family systems therapy" but goes beyond it--suggesting a new paradigm, new terminology, and a new teaching perspective. It discusses the historical background of family therapy training, a scientific foundation for what…

Optimizing the Diagnosis and Management of Dravet Syndrome: Recommendations From a North American Consensus Panel.

PubMed

Wirrell, Elaine C; Laux, Linda; Donner, Elizabeth; Jette, Nathalie; Knupp, Kelly; Meskis, Mary Anne; Miller, Ian; Sullivan, Joseph; Welborn, Michelle; Berg, Anne T

2017-03-01

To establish standards for early, cost-effective, and accurate diagnosis; optimal therapies for seizures; and recommendations for evaluation and management of comorbidities for children and adults with Dravet syndrome, using a modified Delphi process. An expert panel was convened comprising epileptologists with nationally recognized expertise in Dravet syndrome and parents of children with Dravet syndrome, whose experience and understanding was enhanced by their active roles in Dravet syndrome associations. Panelists were asked to base their responses to questions both on their clinical expertise and results of a literature review that was forwarded to each panelist. Three rounds of online questionnaires were conducted to identify areas of consensus and strength of that consensus, as well as areas of contention. The panel consisted of 13 physicians and five family members. Strong consensus was reached regarding typical clinical presentation of Dravet syndrome, range of electroencephalography and magnetic resonance imaging findings, need for genetic testing, critical information that should be conveyed to families at diagnosis, priorities for seizure control and typical degree of control, seizure triggers and recommendations for avoidance, first- and second-line therapies for seizures, requirement and indications for rescue therapy, specific recommendations for comorbidity screening, and need for family support. Consensus was not as strong regarding later therapies, including vagus nerve stimulation and callosotomy, and for specific therapies of associated comorbidities. Beyond the initial treatment with benzodiazepines and use of valproate, there was no consensus on the optimal in-hospital management of convulsive status epilepticus. We were able to identify areas where there was strong consensus that we hope will (1) inform health care providers on optimal diagnosis and management of patients with Dravet syndrome, (2) support reimbursement from insurance companies for genetic testing and Dravet syndrome-specific therapies, and (3) improve quality of life for patients with Dravet syndrome and their families by avoidance of unnecessary testing and provision of an early accurate diagnosis allowing optimal selection of therapeutic strategies. Copyright © 2017 Elsevier Inc. All rights reserved.

Optimization in Radiation Therapy: Applications in Brachytherapy and Intensity Modulated Radiation Therapy

NASA Astrophysics Data System (ADS)

McGeachy, Philip David

Over 50% of cancer patients require radiation therapy (RT). RT is an optimization problem requiring maximization of the radiation damage to the tumor while minimizing the harm to the healthy tissues. This dissertation focuses on two main RT optimization problems: 1) brachytherapy and 2) intensity modulated radiation therapy (IMRT). The brachytherapy research involved solving a non-convex optimization problem by creating an open-source genetic algorithm optimizer to determine the optimal radioactive seed distribution for a given set of patient volumes and constraints, both dosimetric- and implant-based. The optimizer was tested for a set of 45 prostate brachytherapy patients. While all solutions met the clinical standards, they also benchmarked favorably with those generated by a standard commercial solver. Compared to its compatriot, the salient features of the generated solutions were: slightly reduced prostate coverage, lower dose to the urethra and rectum, and a smaller number of needles required for an implant. Historically, IMRT requires modulation of fluence while keeping the photon beam energy fixed. The IMRT-related investigation in this thesis aimed at broadening the solution space by varying photon energy. The problem therefore involved simultaneous optimization of photon beamlet energy and fluence, denoted by XMRT. Formulating the problem as convex, linear programming was applied to obtain solutions for optimal energy-dependent fluences, while achieving all clinical objectives and constraints imposed. Dosimetric advantages of XMRT over single-energy IMRT in the improved sparing of organs at risk (OARs) was demonstrated in simplified phantom studies. The XMRT algorithm was improved to include clinical dose-volume constraints and clinical studies for prostate and head and neck cancer patients were investigated. Compared to IMRT, XMRT provided improved dosimetric benefit in the prostate case, particularly within intermediate- to low-dose regions (≤ 40 Gy) for OARs. For head and neck cases, XMRT solutions showed no significant disadvantage or advantage over IMRT. The deliverability concerns for the fluence maps generated from XMRT were addressed by incorporating smoothing constraints during the optimization and through successful generation of treatment machine files. Further research is needed to explore the full potential of the XMRT approach to RT.

The rationale for microcirculatory guided fluid therapy.

PubMed

Ince, Can

2014-06-01

The ultimate purpose of fluid administration in states of hypovolemia is to correct cardiac output to improve microcirculatory perfusion and tissue oxygenation. Observation of the microcirculation using handheld microscopes gives insight into the nature of convective and diffusive defect in hypovolemia. The purpose of this article is to introduce a new platform for hemodynamic-targeted fluid therapy based on the correction of tissue and microcirculatory perfusion assumed to be at risk during hypovolemia. Targeting systemic hemodynamic targets and/or clinical surrogates of hypovolemia gives inadequate guarantee for the correction of tissue perfusion by fluid therapy especially in conditions of distributive shock as occur in inflammation and sepsis. Findings are presented, which support the idea that only clinical signs of hypovolemia associated with low microcirculatory flow can be expected to benefit from fluid therapy and that fluid overload causes a defect in the diffusion of oxygen transport. We hypothesized that the optimal amount of fluid needed for correction of hypovolemia is defined by a physiologically based functional microcirculatory hemodynamic platform where convection and diffusion need to be optimized. Future clinical trials using handheld microscopes able to automatically evaluate the microcirculation at the bedside will show whether such a platform will indeed optimize fluid therapy.

Extracting Optical Fiber Background from Surface-Enhanced Raman Spectroscopy Spectra Based on Bi-Objective Optimization Modeling.

PubMed

Huang, Jie; Shi, Tielin; Tang, Zirong; Zhu, Wei; Liao, Guanglan; Li, Xiaoping; Gong, Bo; Zhou, Tengyuan

2017-08-01

We propose a bi-objective optimization model for extracting optical fiber background from the measured surface-enhanced Raman spectroscopy (SERS) spectrum of the target sample in the application of fiber optic SERS. The model is built using curve fitting to resolve the SERS spectrum into several individual bands, and simultaneously matching some resolved bands with the measured background spectrum. The Pearson correlation coefficient is selected as the similarity index and its maximum value is pursued during the spectral matching process. An algorithm is proposed, programmed, and demonstrated successfully in extracting optical fiber background or fluorescence background from the measured SERS spectra of rhodamine 6G (R6G) and crystal violet (CV). The proposed model not only can be applied to remove optical fiber background or fluorescence background for SERS spectra, but also can be transferred to conventional Raman spectra recorded using fiber optic instrumentation.

Clinical scale rapid expansion of lymphocytes for adoptive cell transfer therapy in the WAVE® bioreactor

PubMed Central

2012-01-01

Background To simplify clinical scale lymphocyte expansions, we investigated the use of the WAVE®, a closed system bioreactor that utilizes active perfusion to generate high cell numbers in minimal volumes. Methods We have developed an optimized rapid expansion protocol for the WAVE bioreactor that produces clinically relevant numbers of cells for our adoptive cell transfer clinical protocols. Results TIL and genetically modified PBL were rapidly expanded to clinically relevant scales in both static bags and the WAVE bioreactor. Both bioreactors produced comparable numbers of cells; however the cultures generated in the WAVE bioreactor had a higher percentage of CD4+ cells and had a less activated phenotype. Conclusions The WAVE bioreactor simplifies the process of rapidly expanding tumor reactive lymphocytes under GMP conditions, and provides an alternate approach to cell generation for ACT protocols. PMID:22475724

Is narrow-band imaging useful for histological evaluation of gastric mucosa-associated lymphoid tissue lymphoma after treatment?

PubMed

Nonaka, Kouichi; Ohata, Ken; Matsuhashi, Nobuyuki; Shimizu, Michio; Arai, Shin; Hiejima, Yoshimitsu; Kita, Hiroto

2014-05-01

Endoscopic diagnosis of stomach mucosa-associated lymphoid tissue (MALT) lymphoma is often difficult because few specific findings are indicated. Even when MALT lymphoma is suspected by endoscopy, it is still difficult to make a definitive diagnosis by biopsy because lymphoma cells sometimes distribute unevenly. We previously reported that a tree-like appearance (TLA) is a characteristic finding of MALT lymphoma by narrow-band imaging (NBI) magnifying endoscopy and it is valuable in the selection of an optimal biopsy site in MALT lymphoma. Here, we study the frequency of TLA and evaluate the relationship between the response to eradication therapy and TLA in MALT lymphoma. We retrospectively examined the clinical background, endoscopic findings, response to eradication therapy, and Helicobacter pylori infection status of 16 patients diagnosed with MALT lymphoma who were referred to our hospital from April 2007 to August 2012. The regimen for eradicationtherapy consisted of rabeprazole, with amoxicillin and clarithromycin, all given for 7 days. TLA was found in 75% (12/16) and H. pylori infection in 75% (12/16) of patients diagnosed with MALT lymphoma by NBI magnifying endoscopy. In all complete regression (CR) patients after eradication treatment, the TLA finding had disappeared (100%); however, in the non-CR patients, TLA remained the same as before the eradication therapy (P=0.002). These results suggest that NBI magnifying endoscopy may be useful not only in the diagnosis but also in the evaluation of the response to eradication therapy of MALT lymphoma of the stomach. © 2013 The Authors. Digestive Endoscopy © 2013 Japan Gastroenterological Endoscopy Society.

Neural dynamic optimization for control systems. I. Background.

PubMed

Seong, C Y; Widrow, B

2001-01-01

The paper presents neural dynamic optimization (NDO) as a method of optimal feedback control for nonlinear multi-input-multi-output (MIMO) systems. The main feature of NDO is that it enables neural networks to approximate the optimal feedback solution whose existence dynamic programming (DP) justifies, thereby reducing the complexities of computation and storage problems of the classical methods such as DP. This paper mainly describes the background and motivations for the development of NDO, while the two other subsequent papers of this topic present the theory of NDO and demonstrate the method with several applications including control of autonomous vehicles and of a robot arm, respectively.

Optimization of treatment with interferon beta in multiple sclerosis. Usefulness of automatic system application criteria

PubMed Central

Ruiz-Peña, Juan Luís; Duque, Pablo; Izquierdo, Guillermo

2008-01-01

Background A software based tool has been developed (Optem) to allow automatize the recommendations of the Canadian Multiple Sclerosis Working Group for optimizing MS treatment in order to avoid subjective interpretation. Methods Treatment Optimization Recommendations (TORs) were applied to our database of patients treated with IFN β1a IM. Patient data were assessed during year 1 for disease activity, and patients were assigned to 2 groups according to TOR: "change treatment" (CH) and "no change treatment" (NCH). These assessments were then compared to observed clinical outcomes for disease activity over the following years. Results We have data on 55 patients. The "change treatment" status was assigned to 22 patients, and "no change treatment" to 33 patients. The estimated sensitivity and specificity according to last visit status were 73.9% and 84.4%. During the following years, the Relapse Rate was always higher in the "change treatment" group than in the "no change treatment" group (5 y; CH: 0.7, NCH: 0.07; p < 0.001, 12 m – last visit; CH: 0.536, NCH: 0.34). We obtained the same results with the EDSS (4 y; CH: 3.53, NCH: 2.55, annual progression rate in 12 m – last visit; CH: 0.29, NCH: 0.13). Conclusion Applying TOR at the first year of therapy allowed accurate prediction of continued disease activity in relapses and disability progression. PMID:18325088

Immunomodulation to Optimize Vascularized Composite Allograft Integration in Limb Loss Therapy

DTIC Science & Technology

2015-10-01

2 AWARD  NUMBER:        W81XWH-­12-­2-­0058   TITLE:      Immunomodulation to Optimize Vascularized Composite Allograft Integration in Limb Loss...NUMBER   Immunomodulation to Optimize Vascularized Composite Allograft Integration in Limb Loss Therapy 5b.  GRANT  NUMBER   W81XWH-­12-­2-­0058...transplanted   tissues  are  now  available   that  may  greatly   reduce   the   risks  associated   with  limb  transplantation.       The  proposal

The optimization of needle electrode number and placement for irreversible electroporation of hepatocellular carcinoma

PubMed Central

Adeyanju, Oyinlolu O.; Al-Angari, Haitham M.; Sahakian, Alan V.

2012-01-01

Background Irreversible electroporation (IRE) is a novel ablation tool that uses brief high-voltage pulses to treat cancer. The efficacy of the therapy depends upon the distribution of the electric field, which in turn depends upon the configuration of electrodes used. Methods We sought to optimize the electrode configuration in terms of the distance between electrodes, the depth of electrode insertion, and the number of electrodes. We employed a 3D Finite Element Model and systematically varied the distance between the electrodes and the depth of electrode insertion, monitoring the lowest voltage sufficient to ablate the tumor, VIRE. We also measured the amount of normal (non-cancerous) tissue ablated. Measurements were performed for two electrodes, three electrodes, and four electrodes. The optimal electrode configuration was determined to be the one with the lowest VIRE, as that minimized damage to normal tissue. Results The optimal electrode configuration to ablate a 2.5 cm spheroidal tumor used two electrodes with a distance of 2 cm between the electrodes and a depth of insertion of 1 cm below the halfway point in the spherical tumor, as measured from the bottom of the electrode. This produced a VIRE of 3700 V. We found that it was generally best to have a small distance between the electrodes and for the center of the electrodes to be inserted at a depth equal to or deeper than the center of the tumor. We also found the distance between electrodes was far more important in influencing the outcome measures when compared with the depth of electrode insertion. Conclusions Overall, the distribution of electric field is highly dependent upon the electrode configuration, but the optimal configuration can be determined using numerical modeling. Our findings can help guide the clinical application of IRE as well as the selection of the best optimization algorithm to use in finding the optimal electrode configuration. PMID:23077449

[Diagnosis and treatment of metabolic syndrome combined with liver toxicity genesis in contract service officers].

PubMed

Semiserin, V A; Khritinin, D F; Maev, I V; Karakozov, A T; Eremin, M N; Olenicheva, E L

2012-01-01

In this paper is synthesized current and recent data on the problem of metabolic syndrome (MS) in combination with toxic liver injury (CCI). Statistical parameters of the last 15 years, the dynamics of alimentary-constitutional obesity (ABC) in patients from the officers contracted service of Defense Ministry of Russia are reflected. Two-year experience in the application of modern non-invasive methods of diagnosis of liver fibrosis with a reflection of its dynamics on the background of complex treatment of patients with MS in conjunction with the Chamber on the example of 57 patients is shown. Paid great attention to psychological and emotional adjustment of patients with ABC, given the complex survey design and treatment in violation of motivational and behavioral responses. High clinical efficiency of combination drug therapy of MS and CCI, the diagnostic value of modern non-invasive methods of diagnosis of hepatic fibrosis are reliably performed. Technique of elastography significantly improves the liver clinical evaluation of the effectiveness of the therapy, allows for early detect the presence of the initial degree of hepatic fibrosis, choose the optimal treatment regimen and to evaluate the results dynamically.

Music Teachers and Music Therapists: Helping Children Together.

ERIC Educational Resources Information Center

Patterson, Allyson

2003-01-01

Provides background information on music therapy. Discusses how music therapy works in the public school setting and offers advice to music teachers. Explores music therapy and the Individuals with Disabilities Education Act, addressing the benefits of having access to music therapists. (CMK)

Incretin-based therapy in type 2 diabetes: An evidence based systematic review and meta-analysis.

PubMed

Waldrop, Greer; Zhong, Jixin; Peters, Matthew; Goud, Aditya; Chen, Yin-Hsiu; Davis, Stephen N; Mukherjee, Bhramar; Rajagopalan, Sanjay

2018-01-01

Incretin based therapies such as dipeptidyl peptidase-4 inhibitors (DPP-4i) and glucagon-like peptide-1 receptor agonists (GLP-1Ra) are increasingly used for the treatment of Type 2 diabetes mellitus. In clinical practice and in previously performed clinical trials, these agents are often used in combination with other oral anti-diabetic agents (OADs) and Insulin. Prior meta-analytic reviews however do not adequately address the impact of background therapy and active comparator arms. Accordingly, we aimed to further investigate the efficacy of incretin based therapies by updating existing reviews by including clinical trial evidence after 2008; estimating the pooled effect of incretin therapies on glycemic efficacy and weight-loss, stratified by comparator therapy (placebo, mono-therapy, etc.), estimating the impact of background OADs and within class (GLP-1Ra or DPP-4i) comparative efficacy, on glycemia control. 82 randomized controlled trials after 2008 with glycemic control and weight loss as primary end-points were included. Both DPP-4i and GLP-1Ra reduced HbA1c, but only GLP-1Ra caused weight loss when compared to either active comparator drugs or placebo. GLP-1Ra were more effective than DPP-4i in glycemia lowering. Long acting GLP-1Ra were more effective in HbA1c lowering than short-acting agents but with similar weight loss effect. The effect of DPP-4i incretin glycemic efficacy was not modified by background therapy used in the study. Copyright © 2016. Published by Elsevier Inc.

Evaluating optimal therapy robustness by virtual expansion of a sample population, with a case study in cancer immunotherapy

PubMed Central

Barish, Syndi; Ochs, Michael F.; Sontag, Eduardo D.; Gevertz, Jana L.

2017-01-01

Cancer is a highly heterogeneous disease, exhibiting spatial and temporal variations that pose challenges for designing robust therapies. Here, we propose the VEPART (Virtual Expansion of Populations for Analyzing Robustness of Therapies) technique as a platform that integrates experimental data, mathematical modeling, and statistical analyses for identifying robust optimal treatment protocols. VEPART begins with time course experimental data for a sample population, and a mathematical model fit to aggregate data from that sample population. Using nonparametric statistics, the sample population is amplified and used to create a large number of virtual populations. At the final step of VEPART, robustness is assessed by identifying and analyzing the optimal therapy (perhaps restricted to a set of clinically realizable protocols) across each virtual population. As proof of concept, we have applied the VEPART method to study the robustness of treatment response in a mouse model of melanoma subject to treatment with immunostimulatory oncolytic viruses and dendritic cell vaccines. Our analysis (i) showed that every scheduling variant of the experimentally used treatment protocol is fragile (nonrobust) and (ii) discovered an alternative region of dosing space (lower oncolytic virus dose, higher dendritic cell dose) for which a robust optimal protocol exists. PMID:28716945

Rectal cancer: An evidence-based update for primary care providers

PubMed Central

Gaertner, Wolfgang B; Kwaan, Mary R; Madoff, Robert D; Melton, Genevieve B

2015-01-01

Rectal adenocarcinoma is an important cause of cancer-related deaths worldwide, and key anatomic differences between the rectum and the colon have significant implications for management of rectal cancer. Many advances have been made in the diagnosis and management of rectal cancer. These include clinical staging with imaging studies such as endorectal ultrasound and pelvic magnetic resonance imaging, operative approaches such as transanal endoscopic microsurgery and laparoscopic and robotic assisted proctectomy, as well as refined neoadjuvant and adjuvant therapies. For stage II and III rectal cancers, combined chemoradiotherapy offers the lowest rates of local and distant relapse, and is delivered neoadjuvantly to improve tolerability and optimize surgical outcomes, particularly when sphincter-sparing surgery is an endpoint. The goal in rectal cancer treatment is to optimize disease-free and overall survival while minimizing the risk of local recurrence and toxicity from both radiation and systemic therapy. Optimal patient outcomes depend on multidisciplinary involvement for tailored therapy. The successful management of rectal cancer requires a multidisciplinary approach, with the involvement of enterostomal nurses, gastroenterologists, medical and radiation oncologists, radiologists, pathologists and surgeons. The identification of patients who are candidates for combined modality treatment is particularly useful to optimize outcomes. This article provides an overview of the diagnosis, staging and multimodal therapy of patients with rectal cancer for primary care providers. PMID:26167068

Depressed College Students and Tricyclic Antidepressant Therapy.

ERIC Educational Resources Information Center

Brown, Ben Maurice

1978-01-01

Depressed college students representing several distinct diagnostic groups were studied. Evidence indicates that patients with depressive neurosis show optimal treatment outcomes following tricyclic antidepressant therapy. (JMF)

Optimizing Surveillance Performance of Alpha-Fetoprotein by Selection of Proper Target Population in Chronic Hepatitis B

PubMed Central

Chung, Jung Wha; Kim, Beom Hee; Lee, Chung Seop; Kim, Gi Hyun; Sohn, Hyung Rae; Min, Bo Young; Song, Joon Chang; Park, Hyun Kyung; Jang, Eun Sun; Yoon, Hyuk; Kim, Jaihwan; Shin, Cheol Min; Park, Young Soo; Hwang, Jin-Hyeok; Jeong, Sook-Hyang; Kim, Nayoung; Lee, Dong Ho; Lee, Jaebong; Ahn, Soyeon

2016-01-01

Although alpha-fetoprotein (AFP) is the most widely used biomarker in hepatocellular carcinoma (HCC) surveillance, disease activity may also increase AFP levels in chronic hepatitis B (CHB). Since nucleos(t)ide analog (NA) therapy may reduce not only HBV viral loads and transaminase levels but also the falsely elevated AFP levels in CHB, we tried to determine whether exposure to NA therapy influences AFP performance and whether selective application can optimize the performance of AFP testing in CHB during HCC surveillance. A retrospective cohort of 6,453 CHB patients who received HCC surveillance was constructed from the electronic clinical data warehouse. Covariates of AFP elevation were determined from 53,137 AFP measurements, and covariate-specific receiver operating characteristics regression analysis revealed that albumin levels and exposure to NA therapy were independent determinants of AFP performance. C statistics were largest in patients with albumin levels ≥ 3.7 g/dL who were followed without NA therapy during study period, whereas AFP performance was poorest when tested in patients with NA therapy during study and albumin levels were < 3.7 g/dL (difference in C statics = 0.35, p < 0.0001). Contrary to expectation, CHB patients with current or recent exposure to NA therapy showed poorer performance of AFP during HCC surveillance. Combination of concomitant albumin levels and status of NA therapy can identify subgroup of CHB patients who will show optimized AFP performance. PMID:27997559

Therapists' perspectives on optimal treatment for pathological narcissism.

PubMed

Kealy, David; Goodman, Geoff; Rasmussen, Brian; Weideman, Rene; Ogrodniczuk, John S

2017-01-01

This study used Q methodology to explore clinicians' perspectives regarding optimal psychotherapy process in the treatment of pathological narcissism, a syndrome of impaired self-regulation. Participants were 34 psychotherapists of various disciplines and theoretical orientations who reviewed 3 clinical vignettes portraying hypothetical cases of grandiose narcissism, vulnerable narcissism, and panic disorder without pathological narcissism. Participants then used the Psychotherapy Process Q set, a 100-item Q-sort instrument, to indicate their views regarding optimal therapy process for each hypothetical case. By-person principal components analysis with varimax rotation was conducted on all 102 Q-sorts, revealing 4 components representing clinicians' perspectives on ideal therapy processes for narcissistic and non-narcissistic patients. These perspectives were then analyzed regarding their relationship to established therapy models. The first component represented an introspective, relationally oriented therapy process and was strongly correlated with established psychodynamic treatments. The second component, most frequently endorsed for the panic disorder vignette, consisted of a cognitive and alliance-building approach that correlated strongly with expert-rated cognitive-behavioral therapy. The third and fourth components involved therapy processes focused on the challenging interpersonal behaviors associated with narcissistic vulnerability and grandiosity, respectively. The perspectives on therapy processes that emerged in this study reflect different points of emphasis in the treatment of pathological narcissism, and may serve as prototypes of therapist-generated approaches to patients suffering from this issue. The findings suggest several areas for further empirical inquiry regarding psychotherapy with this population. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Development of light ion therapy at the Karolinska Hospital and Institute.

PubMed

Svensson, Hans; Ringborg, Ulrik; Näslund, Ingemar; Brahme, Anders

2004-12-01

Recent developments in radiation therapy have made it possible to optimize the high dose region to cover almost any target volume and shape at the same time as the dose level to adjacent organs at risk is acceptable. Further implementations of IMRT (Intensity Modulated Radiation Therapy), and inverse treatment planning using already available technologies but also foreseeable improved design of therapy accelerators delivering electron- and photon beams, will bring these advances to the benefit of a broad population of cancer patients. Protons will therefore generally not be needed since in most situations the improvement will be insignificant or moderate due to the large lateral penumbra with deep proton therapy. A further step would be to use He-ions, which have only half the penumbra width of protons and still a fairly low-LET in the spread-out Bragg peak. There is however still a group of patients that cannot be helped by these advances as the tumor might be radioresistant for the presently utilized low ionization density beam qualities. The ultimate step in the therapy development process should therefore be to optimize the beam quality for each tumor-normal tissue situation. To facilitate beam quality optimization light ions are needed. It is argued that in many radioresistant tumors a dose-mean LET of 25-50 eV/nm in the target would be optimum as then tumor cells will be lost in the highest proportion through apoptotic cell kill and the superficial tissues will still be irradiated with a fairly low LET. Light ions using Li, Be, B, and C would then be the ideal choice. In this paper a light ion facility is outlined for the Karolinska University Hospital facilitating both dose distribution and beam quality optimization.

Adherence to adjuvant endocrine therapy: is it a factor for ethnic differences in breast cancer outcomes in New Zealand?

PubMed

Seneviratne, Sanjeewa; Campbell, Ian; Scott, Nina; Kuper-Hommel, Marion; Kim, Boa; Pillai, Avinesh; Lawrenson, Ross

2015-02-01

Despite the benefits of adjuvant endocrine therapy for hormone receptor positive breast cancer, many women are non-adherent or discontinue endocrine treatment early. We studied differences in adherence to adjuvant endocrine therapy by ethnicity in a cohort of New Zealand women with breast cancer and its impact on breast cancer outcomes. We analysed data on women (n = 1149) with newly diagnosed hormone receptor positive, non-metastatic, invasive breast cancer who were treated with adjuvant endocrine therapy in the Waikato during 2005-2011. Linked data from the Waikato Breast Cancer Registry and National Pharmaceutical Database were examined to identify differences by ethnicity in adherence to adjuvant endocrine therapy and the effect of sub-optimal adherence on cancer recurrence and mortality. Overall, a high level of adherence of ≥80% was observed among 70.4% of women, which declined from 76.8% to 59.3% from the first to fifth year of treatment. Māori women were significantly more likely to be sub-optimally adherent (<80%) compared with European women (crude rate 37% vs. 28%, p = 0.005, adjusted OR = 1.51, 95% CI 1.04-2.17). Sub-optimal adherence was associated with a significantly higher risk of breast cancer mortality (HR = 1.77, 95% CI 1.05-2.99) and recurrence (HR = 2.14, 95% CI 1.46-3.14). Sub-optimal adherence to adjuvant endocrine therapy was a likely contributor for breast cancer mortality inequity between Māori and European women, and highlights the need for future research to identify effective ways to increase adherence in Māori women. Copyright © 2014 Elsevier Ltd. All rights reserved.

Metacognition in Speech and Language Therapy for Children with Social (Pragmatic) Communication Disorders: Implications for a Theory of Therapy

ERIC Educational Resources Information Center

Gaile, Jacqueline; Adams, Catherine

2018-01-01

Background: Metacognition is a significant component of complex interventions for children who have developmental language disorders. Research into how metacognition operates in the content or process of developmental language therapy delivery is limited. Identification and description of proposed active therapy components, such as metacognition,…

Assisted therapy with dogs in cancer services.

PubMed

2017-06-12

Background [Figure: see text] Healthcare professionals are keen to find alternative therapies to reduce the stress of hospital admissions, especially in the treatment of cancer. Animal-assisted therapy (AAT) involves using animals to help improve patients' health and well-being, and can alleviate stressful situations.

Art and drama: partners in therapy.

PubMed

Irwin, E C; Rubin, J A; Shapiro, M I

1975-01-01

An art-drama therapy group for latency-age boys made possible the exploration of personal symbols and intense fantasies which resulted in a therapeutically powerful and productive experience. This paper describes the background, rationale, and dynamic process of this group. Multimodal expressive arts therapy is supported.

Weighted optimization of irradiance for photodynamic therapy of port wine stains

NASA Astrophysics Data System (ADS)

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.

HIV Drug Resistance Early Warning Indicators in Namibia for Public Health Action

PubMed Central

Jonas, Anna; Gweshe, Justice; Siboleka, Milner; DeKlerk, Michael; Gawanab, Michael; Badi, Alfons; Sumbi, Victor; Pereko, Dawn; Blom, Abraham; Mwinga, Samson; Jordan, Michael R.; Jerger, Logan; Lau, Kiger; Hong, Steven Y.

2013-01-01

Background HIV drug resistance (HIVDR) testing is not routinely available in many resource-limited settings, therefore antiretroviral therapy (ART) program and site factors known to be associated with emergence of HIVDR should be monitored to optimize the quality of patient care and minimize the emergence of preventable HIVDR. Methods In 2010, Namibia selected five World Health Organization Early Warning Indicators (EWIs) and scaled-up monitoring from 9 to 33 ART sites: ART prescribing practices, Patients lost to follow-up (LTFU) at 12 months, Patients switched to a second-line regimen at 12 months, On-time antiretroviral (ARV) drug pick-up, and ARV drug-supply continuity. Results Records allowed reporting on three of the five selected EWIs. 22 of 33 (67%) sites met the target of 100% initiated on appropriate first-line regimens. 17 of 33 (52%) sites met the target of ≤20% LTFU. 15 of 33 (45%) sites met the target of 0% switched to a second-line regimen. Conclusions EWI monitoring directly resulted in public health action which will optimize the quality of care, specifically the strengthening of ART record systems, engagement of ART sites, and operational research for improved adherence assessment and ART patient defaulter tracing. PMID:23762406

Eradication of common pathogens at days 2, 3 and 4 of moxifloxacin therapy in patients with acute bacterial sinusitis

PubMed Central

Ariza, Horacio; Rojas, Ramon; Johnson, Peter; Gower, Richard; Benson, Alice; Herrington, Janet; Perroncel, Renee; Pertel, Peter

2006-01-01

Background Acute bacterial sinusitis (ABS) is a common infection in clinical practice. Data on time to bacteriologic eradication after antimicrobial therapy are lacking for most agents, but are necessary in order to optimize therapy. This was a prospective, single-arm, open-label, multicenter study to determine the time to bacteriologic eradication in ABS patients (maxillary sinusitis) treated with moxifloxacin. Methods Adult patients with radiologically and clinically confirmed ABS received once-daily moxifloxacin 400 mg for 10 days. Middle meatus secretion sampling was performed using nasal endoscopy pre-therapy, and repeated on 3 consecutive days during treatment. Target enrollment was 30 bacteriologically evaluable patients (pre-therapy culture positive for Streptococcus pneumoniae, Haemophilus influenzae or Moraxella catarrhalis and evaluable cultures for at least Day 2 and Day 3 during therapy visits), including at least 10 each with S. pneumoniae or H. influenzae. Results Of 192 patients enrolled, 42 were bacteriologically evaluable, with 48 pathogens isolated. Moxifloxacin was started on Day 1. Baseline bacteria were eradicated in 35/42 (83.3%) patients by day 2, 42/42 (100%) patients by day 3, and 41/42 (97.6%) patients by day 4. In terms of individual pathogens, 12/18 S. pneumoniae, 22/23 H. influenzae and 7/7 M. catarrhalis were eradicated by day 2 (total 41/48; 85.4%), and 18/18 S. pneumoniae and 23/23 H. influenzae were eradicated by day 3. On Day 4, S. pneumoniae was isolated from a patient who had negative cultures on Days 2 and 3. Thus, the Day 4 eradication rate was 47/48 (97.9%). Clinical success was achieved in 36/38 (94.7%) patients at the test of cure visit. Conclusion In patients with ABS (maxillary sinusitis), moxifloxacin 400 mg once daily for 10 days resulted in eradication of baseline bacteria in 83.3% of patients by Day 2, 100% by Day 3 and 97.6% by Day 4. PMID:16646958

Design and Rationale of the LAPLACE-TIMI 57 Trial: A Phase II, Double-Blind, Placebo-Controlled Study of the Efficacy and Tolerability of a Monoclonal Antibody Inhibitor of PCSK9 in Subjects With Hypercholesterolemia on Background Statin Therapy

PubMed Central

Kohli, Payal; Desai, Nihar R.; Giugliano, Robert P.; Kim, Jae B.; Somaratne, Ransi; Huang, Fannie; Knusel, Beat; McDonald, Shannon; Abrahamsen, Timothy; Wasserman, Scott M.; Scott, Robert; Sabatine, Marc S.

2013-01-01

Lowering low-density lipoprotein cholesterol (LDL-C) is a cornerstone for the prevention of atherosclerotic heart disease, improving clinical outcomes and reducing vascular mortality in patients with hypercholesterolemia. The clinical benefits of LDL-C reduction appear to extend even to patients starting with LDL-C as low as 60–80 mg/dL prior to initiating therapy. Statins are the first-line agents for treating hypercholesterolemia and are effective in reducing LDL-C, but many patients are unable to achieve their optimal lipid targets despite intensive statin therapy. Therefore, there has been a strong impetus for the development of novel pharmacologic agents designed to lower LDL-C further in patients already on statin therapy. Genetic mutations resulting in altered cholesterol homeostasis provide valuable information regarding novel approaches for treating hypercholesterolemia. To that end, mutations in proprotein convertase subtilisin/kexin type 9 (PCSK9) were linked to altered levels of LDL-C, illustrating this protein’s role in lipid metabolism. PCSK9 promotes degradation of the LDL receptor, preventing its transport back to the cell surface and thereby increasing circulating LDL-C. Conversely, inhibition of PCSK9 can profoundly decrease circulating LDL-C, and thus is an attractive new target for LDL-C–lowering therapy. AMG 145 is a fully human monoclonal immunoglobulin G2 antibody that binds specifically to human PCSK9 and inhibits its interaction with the low-density lipoprotein receptor. In this manuscript, we describe the rationale and design of LDL-C Assessment with PCSK9 Monoclonal Antibody Inhibition Combined With Statin Therapy–Thrombolysis In Myocardial Infarction 57 (LAPLACE-TIMI 57; NCT01380730), a 12-week, randomized, double-blind, dose-ranging, placebo-controlled study designed to assess the safety and efficacy of AMG 145 when added to statin therapy in patients with hypercholesterolemia. PMID:22714699

Use of bisphosphonate therapy for osteoporosis in childhood and adolescence.

PubMed

Batch, J A; Couper, J J; Rodda, C; Cowell, C T; Zacharin, M

2003-03-01

Congenital and acquired forms of osteoporosis in childhood and adolescence can result in morbidity from fracture and pain in childhood, and place an individual at significant risk for problems in adult life. A range of therapies exist for the prevention and treatment of osteoporosis, including optimization of daily calcium intake, adequate vitamin D status, weight-bearing exercise, treatment with sex steroids where delayed puberty is a problem and, more recently, use of bisphosphonate therapy. Intravenous pamidronate therapy (a bisphosphonate) has been shown to reduce fractures and improve bone density in children with osteogenesis imperfecta, and might prove to be of benefit in other osteoporotic conditions in childhood. However, a number of issues regarding the optimal use of bisphosphonate therapy in children and adolescents remain to be resolved, including total annual dose and frequency and duration of administration. Bisphosphonate therapy should, therefore, be used only in the context of a well-run clinical programme with specialist knowledge in the management of osteopenic disorders in childhood.

Proton Therapy

MedlinePlus

... effects of the treatment. top of page What equipment is used? Proton beam therapy uses special machines, ... tumor cells. top of page Who operates the equipment? With backgrounds in mechanical, electrical, software, hardware and ...

Target detection in GPR data using joint low-rank and sparsity constraints

NASA Astrophysics Data System (ADS)

Bouzerdoum, Abdesselam; Tivive, Fok Hing Chi; Abeynayake, Canicious

2016-05-01

In ground penetrating radars, background clutter, which comprises the signals backscattered from the rough, uneven ground surface and the background noise, impairs the visualization of buried objects and subsurface inspections. In this paper, a clutter mitigation method is proposed for target detection. The removal of background clutter is formulated as a constrained optimization problem to obtain a low-rank matrix and a sparse matrix. The low-rank matrix captures the ground surface reflections and the background noise, whereas the sparse matrix contains the target reflections. An optimization method based on split-Bregman algorithm is developed to estimate these two matrices from the input GPR data. Evaluated on real radar data, the proposed method achieves promising results in removing the background clutter and enhancing the target signature.

The use of self-expanding silicone stents in esophageal cancer care: optimal pre-, peri-, and postoperative care.

PubMed

Martin, Robert; Duvall, Ryan; Ellis, Susan; Scoggins, Charles R

2009-03-01

Preoperative nutritional supplementation, management of esophageal leaks, and postoperative anastomotic strictures still remain common problems in the management of esophageal cancer. Jejunal feeding tubes, total parenteral nutrition (TPN) with nasogastric suction, and repeated esophageal dilations remain the most common treatments, respectively. The aim of this study was to evaluate the use of removable silicone stents in (1) the preoperative nutritional optimization during neoadjuvant therapy, (2) the management of perioperative anastomotic leak, and (3) the management of postoperative anastomotic strictures. Review of our prospectively maintained esophageal database identified 15 patients who had removable self-expanding silicone stents placed in the management of one of these three management problems from July 2004 to August 2006. Preoperative therapy: Five patients underwent initial stent placement in preparation for neoadjuvant therapy. Dysphagia relief was seen in 100% of patients, with optimal caloric needs taken within 24 h of placement. All patients tolerated neoadjuvant therapy without delay from dehydration or malnutrition. One stent migration was found at the time of operation, which was removed without sequelae. Perioperative therapy: Five patients developed delayed (>10 days) esophageal leaks that were managed with removable esophageal stent and percutaneous drainage (in three patients). All patients had successful exclusion of the leak on the day of the procedure with resumption of oral intake on the evening of procedure. All five healed leaks without sequelae. Postoperative therapy: Five patients developed postoperative anastomotic strictures that required dilation and placement of removable esophageal stent. The median number of dilations was 1 (range 1-2), with all stents placed for approximate 3 months duration. All patients had immediate dysphagia relief after stent placement. Removable esophageal stents are novel treatment option to optimize relief of symptoms and return the patients back to a more normal oral intake. Continued evaluation is needed to consider stent use as first-line therapy.

Mean-variance model for portfolio optimization with background risk based on uncertainty theory

NASA Astrophysics Data System (ADS)

Zhai, Jia; Bai, Manying

2018-04-01

The aim of this paper is to develop a mean-variance model for portfolio optimization considering the background risk, liquidity and transaction cost based on uncertainty theory. In portfolio selection problem, returns of securities and assets liquidity are assumed as uncertain variables because of incidents or lacking of historical data, which are common in economic and social environment. We provide crisp forms of the model and a hybrid intelligent algorithm to solve it. Under a mean-variance framework, we analyze the portfolio frontier characteristic considering independently additive background risk. In addition, we discuss some effects of background risk and liquidity constraint on the portfolio selection. Finally, we demonstrate the proposed models by numerical simulations.

Optimal Implantable Cardioverter Defibrillator Programming.

PubMed

Shah, Bindi K

Optimal programming of implantable cardioverter defibrillators (ICDs) is essential to appropriately treat ventricular tachyarrhythmias and to avoid unnecessary and inappropriate shocks. There have been a series of large clinical trials evaluating tailored programming of ICDs. We reviewed the clinical trials evaluating ICD therapies and detection, and the consensus statement on ICD programming. In doing so, we found that prolonged ICD detection times, higher rate cutoffs, and antitachycardia pacing (ATP) programming decreases inappropriate and painful therapies in a primary prevention population. The use of supraventricular tachyarrhythmia discriminators can also decrease inappropriate shocks. Tailored ICD programming using the knowledge gained from recent ICD trials can decrease inappropriate and unnecessary ICD therapies and decrease mortality.

Statistically designed nonionic surfactant vesicles for dermal delivery of itraconazole: characterization and in vivo evaluation using a standardized Tinea pedis infection model.

PubMed

Kumar, Neeraj; Goindi, Shishu

2014-09-10

The study aims to statistically develop a hydrogel of itraconazole loaded nonionic surfactant vesicles (NSVs) for circumventing the shortcomings and adverse effects of currently used therapies. Influential factors were screened using first-order Taguchi design, thereafter, optimization was performed via D-optimal design involving screened factors (surfactant type, content and molar ratio of cholesterol: surfactant). Response variables investigated were percent drug entrapment, vesicle size, drug skin retention and permeation in 6h. Suspensions of NSVs were gelled to improve topical applicability. Characterization of formulations was performed using vesicle shape, size, surface charge, texture analysis and rheology behavior. Ex vivo studies in rat skin depicted that optimized formulation augmented drug skin retention and permeation in 6h than conventional cream and oily solution of itraconazole. Standardized Tinea pedis model in Wistar rats exhibited in vivo antifungal efficacy of optimized formulation, observed in terms of physical manifestations, fungal-burden score and histopathological profiles. Also, a unique investigation involving studying local oxidative stress of infected paw skins as an indicator of fungal infection was performed. Rapid alleviation of infection in animals treated with optimized hydrogel was observed in comparison to commonly prescribed therapies. Therefore, the optimized NSVs may be a promising and efficient alternative to available antifungal therapies. Copyright © 2014 Elsevier B.V. All rights reserved.

Grey-Markov prediction model based on background value optimization and central-point triangular whitenization weight function

NASA Astrophysics Data System (ADS)

Ye, Jing; Dang, Yaoguo; Li, Bingjun

2018-01-01

Grey-Markov forecasting model is a combination of grey prediction model and Markov chain which show obvious optimization effects for data sequences with characteristics of non-stationary and volatility. However, the state division process in traditional Grey-Markov forecasting model is mostly based on subjective real numbers that immediately affects the accuracy of forecasting values. To seek the solution, this paper introduces the central-point triangular whitenization weight function in state division to calculate possibilities of research values in each state which reflect preference degrees in different states in an objective way. On the other hand, background value optimization is applied in the traditional grey model to generate better fitting data. By this means, the improved Grey-Markov forecasting model is built. Finally, taking the grain production in Henan Province as an example, it verifies this model's validity by comparing with GM(1,1) based on background value optimization and the traditional Grey-Markov forecasting model.

A Systematic Review of the Evidence Regarding Cognitive Therapy Skills That Assist Cognitive Behavioural Therapy in Adults Who Have an Intellectual Disability

ERIC Educational Resources Information Center

Cooney, Patricia; Tunney, Conall; O'Reilly, Gary

2018-01-01

Background: Cognitive behavioural therapy (CBT) is being increasingly adapted for use with people who have an intellectual disability. However, it remains unclear whether inherent cognitive deficits that are present in adults who have an intellectual disability preclude the use of cognitive-based therapies. This review aims to systematically…

Effects of Music Therapy for Children and Adolescents with Psychopathology: A Meta-analysis

ERIC Educational Resources Information Center

Gold, Christian; Voracek, Martin; Wigram, Tony

2004-01-01

Background: The objectives of this review were to examine the overall efficacy of music therapy for children and adolescents with psychopathology, and to examine how the size of the effect of music therapy is influenced by the type of pathology, client's age, music therapy approach, and type of outcome. Method: Eleven studies were included for…

Incorporating uncertainty and motion in Intensity Modulated Radiation Therapy treatment planning

NASA Astrophysics Data System (ADS)

Martin, Benjamin Charles

In radiation therapy, one seeks to destroy a tumor while minimizing the damage to surrounding healthy tissue. Intensity Modulated Radiation Therapy (IMRT) uses overlapping beams of x-rays that add up to a high dose within the target and a lower dose in the surrounding healthy tissue. IMRT relies on optimization techniques to create high quality treatments. Unfortunately, the possible conformality is limited by the need to ensure coverage even if there is organ movement or deformation. Currently, margins are added around the tumor to ensure coverage based on an assumed motion range. This approach does not ensure high quality treatments. In the standard IMRT optimization problem, an objective function measures the deviation of the dose from the clinical goals. The optimization then finds the beamlet intensities that minimize the objective function. When modeling uncertainty, the dose delivered from a given set of beamlet intensities is a random variable. Thus the objective function is also a random variable. In our stochastic formulation we minimize the expected value of this objective function. We developed a problem formulation that is both flexible and fast enough for use on real clinical cases. While working on accelerating the stochastic optimization, we developed a technique of voxel sampling. Voxel sampling is a randomized algorithms approach to a steepest descent problem based on estimating the gradient by only calculating the dose to a fraction of the voxels within the patient. When combined with an automatic sampling rate adaptation technique, voxel sampling produced an order of magnitude speed up in IMRT optimization. We also develop extensions of our results to Intensity Modulated Proton Therapy (IMPT). Due to the physics of proton beams the stochastic formulation yields visibly different and better plans than normal optimization. The results of our research have been incorporated into a software package OPT4D, which is an IMRT and IMPT optimization tool that we developed.

76 FR 31338 - Agency Information Collection Activities: Proposed Collection; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-31

... beneficiary's medications, including prescription and over-the-counter (OTC) medications, herbal therapies, and dietary supplements, which is intended to aid in assessing medication therapy and optimizing...

The role of systemic therapy in the management of sinonasal cancer: A critical review.

PubMed

Bossi, Paolo; Saba, Nabil F; Vermorken, Jan B; Strojan, Primoz; Pala, Laura; de Bree, Remco; Rodrigo, Juan Pablo; Lopez, Fernando; Hanna, Ehab Y; Haigentz, Missak; Takes, Robert P; Slootweg, Piet J; Silver, Carl E; Rinaldo, Alessandra; Ferlito, Alfio

2015-12-01

Due to the rarity and the variety of histological types of sinonasal cancers, there is a paucity of data regarding strategy for their optimal treatment. Generally, outcomes of advanced and higher grade tumors remain unsatisfactory, despite the employment of sophisticated surgical approaches, technical advances in radiation techniques and the use of heavy ion particles. In this context, we critically evaluated the role of systemic therapy as part of a multidisciplinary approach to locally advanced disease. Induction chemotherapy has shown encouraging activity and could have a role in the multimodal treatment of patients with advanced sinonasal tumors. For epithelial tumors, the most frequently employed chemotherapy is cisplatin, in combination with either 5-fluorouracil, taxane, ifosfamide, or vincristine. Only limited experiences with concurrent chemoradiation exist with sinonasal cancer. The role of systemic treatment for each histological type (intestinal-type adenocarcinoma, sinonasal undifferentiated carcinoma, sinonasal neuroendocrine carcinoma, olfactory neuroblastoma, sinonasal primary mucosal melanoma, sarcoma) is discussed. The treatment of SNC requires a multimodal approach. Employment of systemic therapy for locally advanced disease could result in better outcomes, and optimize the therapeutic armamentarium. Further studies are needed to precisely define the role of systemic therapy and identify the optimal sequencing for its administration in relation to local therapies. Copyright © 2015 Elsevier Ltd. All rights reserved.

Evolution of Biomarker Guided Therapy for Heart Failure: Current Concepts and Trial Evidence

PubMed Central

Pruett, Amanda E; Lee, Amanda K; Patterson, Herbert; Schwartz, Todd A; Glotzer, Jana M; Adams, Jr, Kirkwood F

2015-01-01

Optimizing management of patients with heart failure remains quite challenging despite many significant advances in drug and device therapy for this syndrome. Although a large body of evidence from robust clinical trials supports multiple thera-pies, utilization of these well-established treatments remains inconsistent and outcomes suboptimal in “real-world” patients with heart failure. Disease management programs may be effective, but are difficult to implement due to cost and logistical issues. Another approach to optimizing therapy is to utilize biomarkers to guide therapeutic choices. Natriuretic peptides pro-vide additional information of significant clinical value in the diagnosis and estimation of risk inpatients with heart failure. Ongoing research suggests a potential important added role for natriuretic peptides in heart failure. Guiding therapy based on serial changes in these biomarkers may be an effective strategy to optimize treatment and achieve better outcomes in this syn-drome. Initial, innovative, proof-of-concept studies have provided encouraging results and important insights into key as-pects of this strategy, but well designed, large-scale, multicenter, randomized, outcome trials are needed to definitively estab-lish this novel approach to management. Given the immense and growing public health burden of heart failure, identification of cost-effective ways to decrease the morbidity and mortality due to this syndrome is critical. PMID:24251462

Update 2014: advances to optimize 6-mercaptopurine and azathioprine to reduce toxicity and improve efficacy in the management of IBD.

PubMed

Amin, Jaimin; Huang, Brian; Yoon, Jessica; Shih, David Q

2015-02-01

The thiopurine drugs, 6-mercaptopurine (6-MP) and azathioprine (AZA), remain as a mainstay therapy in inflammatory bowel disease (IBD). Differences in metabolism of these drugs lead to individual variation in thiopurine metabolite levels that can determine its therapeutic efficacy and development of adverse reactions. In this update, we will review thiopurine metabolic pathway along with the up-to-date approaches in administering thiopurine medications based on the current literature. A search of the PubMed database by 2 independent reviewers identifying 98 articles evaluating thiopurine metabolism and IBD management. Monitoring thiopurine metabolites can assist physicians in optimizing 6-MP and AZA therapy in treating patients with IBD. Of the dosing strategies reviewed, we found evidence for monitoring thiopurine metabolite level, use of allopurinol with thiopurine, use of mesalamine with thiopurine, combination therapy with thiopurine and anti-tumor necrosis factor agents, and split dosing of AZA or 6-MP to optimize thiopurine therapy and minimize adverse effects in IBD. Based on the currently available literature, various dosing strategies to improve therapeutic response and reduce adverse reactions can be considered, including use of allopurinol with thiopurine, use of mesalamine with thiopurine, combination therapy with thiopurine and anti-tumor necrosis factor agents, and split dosing of thiopurine.

Positive Art Therapy: Linking Positive Psychology to Art Therapy Theory, Practice, and Research

ERIC Educational Resources Information Center

Wilkinson, Rebecca A.; Chilton, Gioia

2013-01-01

As a growing movement in the larger field of mental health, positive psychology has much to offer the art therapy profession, which in turn is uniquely poised to contribute to the study of optimal functioning. This article discusses the relationship of positive psychology to art therapy and its capacity to mobilize client strengths, to induce…

Comparative effectiveness of Tai Chi versus physical therapy for knee osteoarthritis: a randomized trial

USDA-ARS?s Scientific Manuscript database

Background: Few remedies effectively treat long-term pain and disability from knee osteoarthritis. Studies suggest that Tai Chi alleviates symptoms, but no trials have directly compared Tai Chi with standard therapies for osteoarthritis. Objective: To compare Tai Chi with standard physical therapy f...

Reflections on Clinical Learning in Novice Speech-Language Therapy Students

ERIC Educational Resources Information Center

Hill, Anne E.; Davidson, Bronwyn J.; Theodoros, Deborah G.

2012-01-01

Background: Reflective practice is reported to enhance clinical reasoning and therefore to maximize client outcomes. The inclusion of targeted reflective practice in academic programmes in speech-language therapy has not been consistent, although providing opportunities for speech-language therapy students to reflect during their clinical practice…

Cognitive Therapy Abilities in People with Learning Disabilities

ERIC Educational Resources Information Center

Sams, Kathryn; Collins, Suzanne; Reynolds, Shirley

2006-01-01

Background: There is a need to develop and adapt therapies for use with people with learning disabilities who have mental health problems. Aims: To examine the performance of people with learning disabilities on two cognitive therapy tasks (emotion recognition and discrimination among thoughts, feelings and behaviours). We hypothesized that…

Physical Therapy for an Adult with Chronic Stroke after Botulinum Toxin Injection for Spasticity: A Case Report

PubMed Central

Phadke, Chetan P.; Ismail, Farooq; Boulias, Chris

2015-01-01

ABSTRACT Purpose: In this case report, we describe the type and duration of a physical therapy and botulinum toxin type A (BoNTA) intervention directed at lower limb spasticity and the gait and balance improvement in a patient post-stroke. Treatment of focal spasticity with BoNTA intramuscular injections combined with physical therapy is recommended by rehabilitation experts. However, the optimal type and duration of physical therapy intervention to optimize any functional gains that follow chemodenervation induced by BoNTA has not been established. Method: One individual with chronic stroke who received BoNTA injections for upper and lower extremity spasticity was included. Physical therapy intervention consisted of 45- to 60-min sessions twice weekly for 12 weeks, based on the Bobath–neurodevelopmental therapy approach, and an activity-based home program. Results: After BoNTA injections and physical therapy, the patient made clinically significant improvements in balance and gait speed and became more independent with his ambulation. Conclusions: This case report demonstrates that physical therapy after BoNTA injections can result in significant functional improvements for individuals with spasticity after chronic stroke that may not be possible with BoNTA injections alone. PMID:25931655

Radiobiological Optimization of Combination Radiopharmaceutical Therapy Applied to Myeloablative Treatment of Non-Hodgkin’s Lymphoma

PubMed Central

Hobbs, Robert F; Wahl, Richard L; Frey, Eric C; Kasamon, Yvette; Song, Hong; Huang, Peng; Jones, Richard J; Sgouros, George

2014-01-01

Combination treatment is a hallmark of cancer therapy. Although the rationale for combination radiopharmaceutical therapy was described in the mid ‘90s, such treatment strategies have only been implemented clinically recently, and without a rigorous methodology for treatment optimization. Radiobiological and quantitative imaging-based dosimetry tools are now available that enable rational implementation of combined targeted radiopharmaceutical therapy. Optimal implementation should simultaneously account for radiobiological normal organ tolerance while optimizing the ratio of two different radiopharmaceuticals required to maximize tumor control. We have developed such a methodology and applied it to hypothetical myeloablative treatment of non-hodgkin’s lymphoma (NHL) patients using 131I-tositumomab and 90Y-ibritumomab tiuxetan. Methods The range of potential administered activities (AA) is limited by the normal organ maximum tolerated biologic effective doses (MTBEDs) arising from the combined radiopharmaceuticals. Dose limiting normal organs are expected to be the lungs for 131I-tositumomab and the liver for 90Y-ibritumomab tiuxetan in myeloablative NHL treatment regimens. By plotting the limiting normal organ constraints as a function of the AAs and calculating tumor biological effective dose (BED) along the normal organ MTBED limits, the optimal combination of activities is obtained. The model was tested using previously acquired patient normal organ and tumor kinetic data and MTBED values taken from the literature. Results The average AA values based solely on normal organ constraints was (19.0 ± 8.2) GBq with a range of 3.9 – 36.9 GBq for 131I-tositumomab, and (2.77 ± 1.64) GBq with a range of 0.42 – 7.54 GBq for 90Y-ibritumomab tiuxetan. Tumor BED optimization results were calculated and plotted as a function of AA for 5 different cases, established using patient normal organ kinetics for the two radiopharmaceuticals. Results included AA ranges which would deliver 95 % of the maximum tumor BED, which allows for informed inclusion of clinical considerations, such as a maximum allowable 131I administration. Conclusions A rational approach for combination radiopharmaceutical treatment has been developed within the framework of a proven 3-dimensional personalized dosimetry software, 3D-RD, and applied to the myeloablative treatment of NHL. We anticipate combined radioisotope therapy will ultimately supplant single radioisotope therapy, much as combination chemotherapy has substantially replaced single agent chemotherapy. PMID:23918734

TU-EF-304-07: Monte Carlo-Based Inverse Treatment Plan Optimization for Intensity Modulated Proton Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Y; UT Southwestern Medical Center, Dallas, TX; Tian, Z

2015-06-15

Purpose: Intensity-modulated proton therapy (IMPT) is increasingly used in proton therapy. For IMPT optimization, Monte Carlo (MC) is desired for spots dose calculations because of its high accuracy, especially in cases with a high level of heterogeneity. It is also preferred in biological optimization problems due to the capability of computing quantities related to biological effects. However, MC simulation is typically too slow to be used for this purpose. Although GPU-based MC engines have become available, the achieved efficiency is still not ideal. The purpose of this work is to develop a new optimization scheme to include GPU-based MC intomore » IMPT. Methods: A conventional approach using MC in IMPT simply calls the MC dose engine repeatedly for each spot dose calculations. However, this is not the optimal approach, because of the unnecessary computations on some spots that turned out to have very small weights after solving the optimization problem. GPU-memory writing conflict occurring at a small beam size also reduces computational efficiency. To solve these problems, we developed a new framework that iteratively performs MC dose calculations and plan optimizations. At each dose calculation step, the particles were sampled from different spots altogether with Metropolis algorithm, such that the particle number is proportional to the latest optimized spot intensity. Simultaneously transporting particles from multiple spots also mitigated the memory writing conflict problem. Results: We have validated the proposed MC-based optimization schemes in one prostate case. The total computation time of our method was ∼5–6 min on one NVIDIA GPU card, including both spot dose calculation and plan optimization, whereas a conventional method naively using the same GPU-based MC engine were ∼3 times slower. Conclusion: A fast GPU-based MC dose calculation method along with a novel optimization workflow is developed. The high efficiency makes it attractive for clinical usages.« less

Successful Optimization of Adalimumab Therapy in Refractory Uveitis Due to Behçet's Disease.

PubMed

Martín-Varillas, José Luis; Calvo-Río, Vanesa; Beltrán, Emma; Sánchez-Bursón, Juan; Mesquida, Marina; Adán, Alfredo; Hernandez, María Victoria; Garfella, Marisa Hernández; Pascual, Elia Valls; Martínez-Costa, Lucía; Sellas-Fernández, Agustí; Cordero-Coma, Miguel; Díaz-Llopis, Manuel; Gallego, Roberto; Salom, David; Ortego, Norberto; García-Serrano, José L; Callejas-Rubio, José-Luis; Herreras, José M; García-Aparicio, Ángel; Maíz, Olga; Blanco, Ana; Torre, Ignacio; Díaz-Valle, David; Pato, Esperanza; Aurrecoechea, Elena; Caracuel, Miguel A; Gamero, Fernando; Minguez, Enrique; Carrasco-Cubero, Carmen; Olive, Alejandro; Vázquez, Julio; Ruiz-Moreno, Oscar; Manero, Javier; Muñoz-Fernández, Santiago; Martinez, Myriam Gandía; Rubio-Romero, Esteban; Toyos-Sáenz de Miera, F Javier; López Longo, Francisco Javier; Nolla, Joan M; Revenga, Marcelino; González-Vela, Carmen; Loricera, Javier; Atienza-Mateo, Belén; Demetrio-Pablo, Rosalía; Hernández, José Luis; González-Gay, Miguel A; Blanco, Ricardo

2018-03-27

To assess efficacy, safety, and cost-effectiveness of adalimumab (ADA) therapy optimization in a large series of patients with uveitis due to Behçet disease (BD) who achieved remission after the use of this biologic agent. Open-label multicenter study of ADA-treated patients with BD uveitis refractory to conventional immunosuppressants. Sixty-five of 74 patients with uveitis due to BD, who achieved remission after a median ADA duration of 6 (range, 3-12) months. ADA was optimized in 23 (35.4%) of them. This biologic agent was maintained at a dose of 40 mg/subcutaneously/2 weeks in the remaining 42 patients. After remission, based on a shared decision between the patient and the treating physician, ADA was optimized. When agreement between patient and physician was reached, optimization was performed by prolonging the ADA dosing interval progressively. Comparison between optimized and nonoptimized patients was performed. Efficacy, safety, and cost-effectiveness in optimized and nonoptimized groups. To determine efficacy, intraocular inflammation (anterior chamber cells, vitritis, and retinal vasculitis), macular thickness, visual acuity, and the sparing effect of glucocorticoids were assessed. No demographic or ocular differences were found at the time of ADA onset between the optimized and the nonoptimized groups. Most ocular outcomes were similar after a mean ± standard deviation follow-up of 34.7±13.3 and 26±21.3 months in the optimized and nonoptimized groups, respectively. However, relevant adverse effects were only seen in the nonoptimized group (lymphoma, pneumonia, severe local reaction at the injection site, and bacteremia by Escherichia coli, 1 each). Moreover, the mean ADA treatment costs were lower in the optimized group than in the nonoptimized group (6101.25 euros/patient/year vs. 12 339.48; P < 0.01). ADA optimization in BD uveitis refractory to conventional therapy is effective, safe, and cost-effective. Copyright © 2018 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Monte-Carlo background simulations of present and future detectors in x-ray astronomy

NASA Astrophysics Data System (ADS)

Tenzer, C.; Kendziorra, E.; Santangelo, A.

2008-07-01

Reaching a low-level and well understood internal instrumental background is crucial for the scientific performance of an X-ray detector and, therefore, a main objective of the instrument designers. Monte-Carlo simulations of the physics processes and interactions taking place in a space-based X-ray detector as a result of its orbital environment can be applied to explain the measured background of existing missions. They are thus an excellent tool to predict and optimize the background of future observatories. Weak points of a design and the main sources of the background can be identified and methods to reduce them can be implemented and studied within the simulations. Using the Geant4 Monte-Carlo toolkit, we have created a simulation environment for space-based detectors and we present results of such background simulations for XMM-Newton's EPIC pn-CCD camera. The environment is also currently used to estimate and optimize the background of the future instruments Simbol-X and eRosita.

Optimizing Patient Management and Adherence for Children Receiving Growth Hormone.

PubMed

Acerini, Carlo L; Wac, Katarzyna; Bang, Peter; Lehwalder, Dagmar

2017-01-01

Poor adherence with growth hormone (GH) therapy has been associated with worse clinical outcomes, which in children relates specifically to their linear growth and loss of quality of life. The "360° GH in Europe" meeting, held in Lisbon, Portugal, in June 2016 and funded by Merck KGaA (Germany), examined many aspects of GH diseases. The three sessions, entitled " Short Stature Diagnosis and Referral ," " Optimizing Patient Management ," and " Managing Transition ," each benefited from three guest speaker presentations, followed by an open discussion and are reported as a manuscript, authored by the speakers. Reported here is a summary of the proceedings of the second session, which reviewed the determinants of GH therapy response, factors affecting GH therapy adherence and the development of innovative technologies to improve GH treatment in children. Response to GH therapy varies widely, particularly in regard to the underlying diagnosis, although there is little consensus on the definition of a poor response. If the growth response is seen to be less than expected, the possible reasons should be discussed with patients and their parents, including compliance with the therapy regimen. Understanding and addressing the multiple factors that influence adherence, in order to optimize GH therapy, requires a multi-disciplinary approach. Because therapy continues over many years, various healthcare professionals will be involved at different periods of the patient's journey. The role of the injection device for GH therapy, frequent monitoring of response, and patient support are all important for maintaining adherence. New injection devices are incorporating electronic technologies for automated monitoring and recording of clinically relevant information on injections. Study results are indicating that such devices can at least maintain GH adherence; however, acceptance of novel devices needs to be assessed and there remains an on-going need for innovations.

Linear energy transfer incorporated intensity modulated proton therapy optimization

NASA Astrophysics Data System (ADS)

Cao, Wenhua; Khabazian, Azin; Yepes, Pablo P.; Lim, Gino; Poenisch, Falk; Grosshans, David R.; Mohan, Radhe

2018-01-01

The purpose of this study was to investigate the feasibility of incorporating linear energy transfer (LET) into the optimization of intensity modulated proton therapy (IMPT) plans. Because increased LET correlates with increased biological effectiveness of protons, high LETs in target volumes and low LETs in critical structures and normal tissues are preferred in an IMPT plan. However, if not explicitly incorporated into the optimization criteria, different IMPT plans may yield similar physical dose distributions but greatly different LET, specifically dose-averaged LET, distributions. Conventionally, the IMPT optimization criteria (or cost function) only includes dose-based objectives in which the relative biological effectiveness (RBE) is assumed to have a constant value of 1.1. In this study, we added LET-based objectives for maximizing LET in target volumes and minimizing LET in critical structures and normal tissues. Due to the fractional programming nature of the resulting model, we used a variable reformulation approach so that the optimization process is computationally equivalent to conventional IMPT optimization. In this study, five brain tumor patients who had been treated with proton therapy at our institution were selected. Two plans were created for each patient based on the proposed LET-incorporated optimization (LETOpt) and the conventional dose-based optimization (DoseOpt). The optimized plans were compared in terms of both dose (assuming a constant RBE of 1.1 as adopted in clinical practice) and LET. Both optimization approaches were able to generate comparable dose distributions. The LET-incorporated optimization achieved not only pronounced reduction of LET values in critical organs, such as brainstem and optic chiasm, but also increased LET in target volumes, compared to the conventional dose-based optimization. However, on occasion, there was a need to tradeoff the acceptability of dose and LET distributions. Our conclusion is that the inclusion of LET-dependent criteria in the IMPT optimization could lead to similar dose distributions as the conventional optimization but superior LET distributions in target volumes and normal tissues. This may have substantial advantages in improving tumor control and reducing normal tissue toxicities.

On-line Adaptive Radiation Treatment of Prostate Cancer

DTIC Science & Technology

2009-01-01

12]. For intensity modulated radiation therapy (IMRT) plans , the beamlet weight can be re-optimized on a daily basis to mini- mize the dose to the OAR...Thongphiew D, Wang Z, Mathayomchan B, Chankong V, Yoo S, et al. On-line re-optimization of prostate IMRT plans for adaptive radiation therapy . Phys Med Biol...time. The treatment planning method for VMAT however is not mature. We are developing a robust VMAT treatment planning method which incorporates

Role of functional imaging in treatment plan optimization of stereotactic body radiation therapy for liver cancer.

PubMed

De Bari, Berardino; Jumeau, Raphael; Deantonio, Letizia; Adib, Salim; Godin, Sarah; Zeverino, Michele; Moeckli, Raphael; Bourhis, Jean; Prior, John O; Ozsahin, Mahmut

2016-10-13

We report the first known instance of the clinical use of 99mTc-mebrofenin hepatobiliary scintigraphy (HBS) for the optimization of radiotherapy treatment planning and for the follow-up of acute toxicity in a patient undergoing stereotactic body radiation therapy for hepatocellular carcinoma. In our experience, HBS allowed the identification and the sparing of more functioning liver areas, thus potentially reducing the risk of radiation-induced liver toxicity.

Optimizing hydroxyurea therapy for sickle cell anemia.

PubMed

Ware, Russell E

2015-01-01

Hydroxyurea has proven efficacy in numerous clinical trials as a disease-modifying treatment for patients with sickle cell anemia (SCA) but is currently under-used in clinical practice. To improve the effectiveness of hydroxyurea therapy, efforts should be directed toward broadening the clinical treatment indications, optimizing the daily dosage, and emphasizing the benefits of early and extended treatment. Here, various issues related to hydroxyurea treatment are discussed, focusing on both published evidence and clinical experience. Specific guidance is provided regarding important but potentially unfamiliar aspects of hydroxyurea treatment for SCA, such as escalating to maximum tolerated dose, treating in the setting of cerebrovascular disease, switching from chronic transfusions to hydroxyurea, and using serial phlebotomy to alleviate iron overload. Future research directions to optimize hydroxyurea therapy are also discussed, including personalized dosing based on pharmacokinetic modeling, prediction of fetal hemoglobin responses based on pharmacogenomics, and the risks and benefits of hydroxyurea for non-SCA genotypes and during pregnancy/lactation. Another critical initiative is the introduction of hydroxyurea safely and effectively into global regions that have a high disease burden of SCA but limited resources, such as sub-Saharan Africa, the Caribbean, and India. Final considerations emphasize the long-term goal of optimizing hydroxyurea therapy, which is to help treatment become accepted as standard of care for all patients with SCA. © 2015 by The American Society of Hematology. All rights reserved.

Developing an Outcome Measure With High Luminance for Optogenetics Treatment of Severe Retinal Degenerations and for Gene Therapy of Cone Diseases.

PubMed

Cideciyan, Artur V; Roman, Alejandro J; Jacobson, Samuel G; Yan, Boyuan; Pascolini, Michele; Charng, Jason; Pajaro, Simone; Nirenberg, Sheila

2016-06-01

To present stimuli with varied sizes, colors, and patterns over a large range of luminance. The filter bar used in scotopic MP1 was replaced with a custom slide-in tray that introduces light from an external projector driven by an additional computer. MP1 software was modified to provide retinal tracking information to the computer driving the projector. Retinal tracking performance was evaluated by imaging the system input and the output simultaneously with a high-speed video system. Spatial resolution was measured with achromatic and chromatic grating/background combinations over scotopic and photopic ranges. The range of retinal illuminance achievable by the modification was up to 6.8 log photopic Trolands (phot-Td); however, in the current work, only a lower range over -4 to +3 log phot-Td was tested in human subjects. Optical magnification was optimized for low-vision testing with gratings from 4.5 to 0.2 cyc/deg. In normal subjects, spatial resolution driven by rods, short wavelength-sensitive (S-) cones, and long/middle wavelength-sensitive (L/M-) cones was obtained by the choice of adapting conditions and wavelengths of grating and background. Data from a patient with blue cone monochromacy was used to confirm mediation. The modified MP1 can be developed into an outcome measure for treatments in patients with severe retinal degeneration, very low vision, and abnormal eye movements such as those for whom treatment with optogenetics is planned, as well as for patients with cone disorders such as blue cone monochromacy for whom treatment with gene therapy is planned to improve L/M-cone function above a normal complement of rod and S-cone function.

Developing an Outcome Measure With High Luminance for Optogenetics Treatment of Severe Retinal Degenerations and for Gene Therapy of Cone Diseases

PubMed Central

Cideciyan, Artur V.; Roman, Alejandro J.; Jacobson, Samuel G.; Yan, Boyuan; Pascolini, Michele; Charng, Jason; Pajaro, Simone; Nirenberg, Sheila

2016-01-01

Purpose To present stimuli with varied sizes, colors, and patterns over a large range of luminance. Methods The filter bar used in scotopic MP1 was replaced with a custom slide-in tray that introduces light from an external projector driven by an additional computer. MP1 software was modified to provide retinal tracking information to the computer driving the projector. Retinal tracking performance was evaluated by imaging the system input and the output simultaneously with a high-speed video system. Spatial resolution was measured with achromatic and chromatic grating/background combinations over scotopic and photopic ranges. Results The range of retinal illuminance achievable by the modification was up to 6.8 log photopic Trolands (phot-Td); however, in the current work, only a lower range over −4 to +3 log phot-Td was tested in human subjects. Optical magnification was optimized for low-vision testing with gratings from 4.5 to 0.2 cyc/deg. In normal subjects, spatial resolution driven by rods, short wavelength-sensitive (S-) cones, and long/middle wavelength-sensitive (L/M-) cones was obtained by the choice of adapting conditions and wavelengths of grating and background. Data from a patient with blue cone monochromacy was used to confirm mediation. Conclusions The modified MP1 can be developed into an outcome measure for treatments in patients with severe retinal degeneration, very low vision, and abnormal eye movements such as those for whom treatment with optogenetics is planned, as well as for patients with cone disorders such as blue cone monochromacy for whom treatment with gene therapy is planned to improve L/M-cone function above a normal complement of rod and S-cone function. PMID:27309625

Effects of Hormone Therapy on Brain Volumes Changes of Postmenopausal Women Revealed by Optimally-Discriminative Voxel-Based Morphometry

PubMed Central

Zhang, Tianhao; Casanova, Ramon; Resnick, Susan M.; Manson, JoAnn E.; Baker, Laura D.; Padual, Claudia B.; Kuller, Lewis H.; Bryan, R. Nick; Espeland, Mark A.; Davatzikos, Christos

2016-01-01

Backgrounds 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. Methods 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. Results 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. Conclusions 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. PMID:26974440

Effective treatment options for musculoskeletal pain in primary care: A systematic overview of current evidence

PubMed Central

Hill, Jonathan C.; Foster, Nadine E.; Protheroe, Joanne

2017-01-01

Background & aims Musculoskeletal pain, the most common cause of disability globally, is most frequently managed in primary care. People with musculoskeletal pain in different body regions share similar characteristics, prognosis, and may respond to similar treatments. This overview aims to summarise current best evidence on currently available treatment options for the five most common musculoskeletal pain presentations (back, neck, shoulder, knee and multi-site pain) in primary care. Methods A systematic search was conducted. Initial searches identified clinical guidelines, clinical pathways and systematic reviews. Additional searches found recently published trials and those addressing gaps in the evidence base. Data on study populations, interventions, and outcomes of intervention on pain and function were extracted. Quality of systematic reviews was assessed using AMSTAR, and strength of evidence rated using a modified GRADE approach. Results Moderate to strong evidence suggests that exercise therapy and psychosocial interventions are effective for relieving pain and improving function for musculoskeletal pain. NSAIDs and opioids reduce pain in the short-term, but the effect size is modest and the potential for adverse effects need careful consideration. Corticosteroid injections were found to be beneficial for short-term pain relief among patients with knee and shoulder pain. However, current evidence remains equivocal on optimal dose, intensity and frequency, or mode of application for most treatment options. Conclusion This review presents a comprehensive summary and critical assessment of current evidence for the treatment of pain presentations in primary care. The evidence synthesis of interventions for common musculoskeletal pain presentations shows moderate-strong evidence for exercise therapy and psychosocial interventions, with short-term benefits only from pharmacological treatments. Future research into optimal dose and application of the most promising treatments is needed. PMID:28640822

Population-based V3 genotypic tropism assay: a retrospective analysis using screening samples from the A4001029 and MOTIVATE studies.

PubMed

McGovern, Rachel A; Thielen, Alexander; Mo, Theresa; Dong, Winnie; Woods, Conan K; Chapman, Douglass; Lewis, Marilyn; James, Ian; Heera, Jayvant; Valdez, Hernan; Harrigan, P Richard

2010-10-23

The MOTIVATE-1 and 2 studies compared maraviroc (MVC) along with optimized background therapy (OBT) vs. placebo along with OBT in treatment-experienced patients screened as having R5-HIV (original Monogram Trofile). A subset screened with non-R5 HIV were treated with MVC or placebo along with OBT in a sister safety trial, A4001029. This analysis retrospectively examined the performance of population-based sequence analysis of HIV-1 env V3-loop to predict coreceptor tropism. Triplicate V3-loop sequences were generated using stored screening plasma samples and data was processed using custom software ('ReCall'), blinded to clinical response. Tropism was inferred using geno2pheno ('g2p'; 5% false positive rate). Primary outcomes were viral load changes after starting maraviroc; and concordance with prior screening Trofile results. Genotype and Trofile results were available for 1164 individuals with virological outcome data (N = 169 non-R5 by Trofile). Compared with Trofile, V3 genotyping had a specificity of 92.6% and a sensitivity of 67.4% for detecting non-R5 virus. However, when compared with clinical outcome, virological responses were consistently similar between Trofile and V3 genotype at weeks 8 and 24 following the initiation of therapy for patients categorized as R5. Despite differences in sensitivity for predicting non-R5 HIV, week 8 and 24 week virological responses were similar in this treatment-experienced population. These findings suggest the potential utility of V3 genotyping as an accessible assay to select patients who may benefit from maraviroc treatment. Optimization of the predictive tropism algorithm may lead to further improvement in the clinical utility of HIV genotypic tropism assays.

Critical Structure Sparing in Stereotactic Ablative Radiotherapy for Central Lung Lesions: Helical Tomotherapy vs. Volumetric Modulated Arc Therapy

PubMed Central

Chi, Alexander; Ma, Pan; Fu, Guishan; Hobbs, Gerry; Welsh, James S.; Nguyen, Nam P.; Jang, Si Young; Dai, Jinrong; Jin, Jing; Komaki, Ritsuko

2013-01-01

Background Helical tomotherapy (HT) and volumetric modulated arc therapy (VMAT) are both advanced techniques of delivering intensity-modulated radiotherapy (IMRT). Here, we conduct a study to compare HT and partial-arc VMAT in their ability to spare organs at risk (OARs) when stereotactic ablative radiotherapy (SABR) is delivered to treat centrally located early stage non-small-cell lung cancer or lung metastases. Methods 12 patients with centrally located lung lesions were randomly chosen. HT, 2 & 8 arc (Smart Arc, Pinnacle v9.0) plans were generated to deliver 70 Gy in 10 fractions to the planning target volume (PTV). Target and OAR dose parameters were compared. Each technique’s ability to meet dose constraints was further investigated. Results HT and VMAT plans generated essentially equivalent PTV coverage and dose conformality indices, while a trend for improved dose homogeneity by increasing from 2 to 8 arcs was observed with VMAT. Increasing the number of arcs with VMAT also led to some improvement in OAR sparing. After normalizing to OAR dose constraints, HT was found to be superior to 2 or 8-arc VMAT for optimal OAR sparing (meeting all the dose constraints) (p = 0.0004). All dose constraints were met in HT plans. Increasing from 2 to 8 arcs could not help achieve optimal OAR sparing for 4 patients. 2/4 of them had 3 immediately adjacent structures. Conclusion HT appears to be superior to VMAT in OAR sparing mainly in cases which require conformal dose avoidance of multiple immediately adjacent OARs. For such cases, increasing the number of arcs in VMAT cannot significantly improve OAR sparing. PMID:23577071

Salient object detection based on discriminative boundary and multiple cues integration

NASA Astrophysics Data System (ADS)

Jiang, Qingzhu; Wu, Zemin; Tian, Chang; Liu, Tao; Zeng, Mingyong; Hu, Lei

2016-01-01

In recent years, many saliency models have achieved good performance by taking the image boundary as the background prior. However, if all boundaries of an image are equally and artificially selected as background, misjudgment may happen when the object touches the boundary. We propose an algorithm called weighted contrast optimization based on discriminative boundary (wCODB). First, a background estimation model is reliably constructed through discriminating each boundary via Hausdorff distance. Second, the background-only weighted contrast is improved by fore-background weighted contrast, which is optimized through weight-adjustable optimization framework. Then to objectively estimate the quality of a saliency map, a simple but effective metric called spatial distribution of saliency map and mean saliency in covered window ratio (MSR) is designed. Finally, in order to further promote the detection result using MSR as the weight, we propose a saliency fusion framework to integrate three other cues-uniqueness, distribution, and coherence from three representative methods into our wCODB model. Extensive experiments on six public datasets demonstrate that our wCODB performs favorably against most of the methods based on boundary, and the integrated result outperforms all state-of-the-art methods.

76 FR 60843 - Agency Information Collection Activities: Submission for OMB Review; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-30

... beneficiary's medications, including prescription and over-the-counter (OTC) medications, herbal therapies, and dietary supplements, which is intended to aid in assessing medication therapy and optimizing...

WE-D-BRD-01: Innovation in Radiation Therapy Delivery: Advanced Digital Linac Features

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xing, L; Wong, J; Li, R

2014-06-15

Last few years has witnessed significant advances in linac technology and therapeutic dose delivery method. Digital linacs equipped with high dose rate FFF beams have been clinically implemented in a number of hospitals. Gated VMAT is becoming increasingly popular in treating tumors affected by respiratory motion. This session is devoted to update the audience with these technical advances and to present our experience in clinically implementing the new linacs and dose delivery methods. Topics to be covered include, technical features of new generation of linacs from different vendors, dosimetric characteristics and clinical need for FFF-beam based IMRT and VMAT, respiration-gatedmore » VMAT, the concept and implementation of station parameter optimized radiation therapy (SPORT), beam level imaging and onboard image guidance tools. Emphasis will be on providing fundamental understanding of the new treatment delivery and image guidance strategies, control systems, and the associated dosimetric characteristics. Commissioning and acceptance experience on these new treatment delivery technologies will be reported. Clinical experience and challenges encountered during the process of implementation of the new treatment techniques and future applications of the systems will also be highlighted. Learning Objectives: Present background knowledge of emerging digital linacs and summarize their key geometric and dosimetric features. SPORT as an emerging radiation therapy modality specifically designed to take advantage of digital linacs. Discuss issues related to the acceptance and commissioning of the digital linacs and FFF beams. Describe clinical utility of the new generation of digital linacs and their future applications.« less

Characterization of scintillator crystals for usage as prompt gamma monitors in particle therapy

NASA Astrophysics Data System (ADS)

Roemer, K.; Pausch, G.; Bemmerer, D.; Berthel, M.; Dreyer, A.; Golnik, C.; Hueso-González, F.; Kormoll, T.; Petzoldt, J.; Rohling, H.; Thirolf, P.; Wagner, A.; Wagner, L.; Weinberger, D.; Fiedler, F.

2015-10-01

Particle therapy in oncology is advantageous compared to classical radiotherapy due to its well-defined penetration depth. In the so-called Bragg peak, the highest dose is deposited; the tissue behind the cancerous area is not exposed. Different factors influence the range of the particle and thus the target area, e.g. organ motion, mispositioning of the patient or anatomical changes. In order to avoid over-exposure of healthy tissue and under-dosage of cancerous regions, the penetration depth of the particle has to be monitored, preferably already during the ongoing therapy session. The verification of the ion range can be performed using prompt gamma emissions, which are produced by interactions between projectile and tissue, and originate from the same location and time of the nuclear reaction. The prompt gamma emission profile and the clinically relevant penetration depth are correlated. Various imaging concepts based on the detection of prompt gamma rays are currently discussed: collimated systems with counting detectors, Compton cameras with (at least) two detector planes, or the prompt gamma timing method, utilizing the particle time-of-flight within the body. For each concept, the detection system must meet special requirements regarding energy, time, and spatial resolution. Nonetheless, the prerequisites remain the same: the gamma energy region (2 to 10 MeV), high counting rates and the stability in strong background radiation fields. The aim of this work is the comparison of different scintillation crystals regarding energy and time resolution for optimized prompt gamma detection.

cRGD Peptide-Conjugated Pyropheophorbide-a Photosensitizers for Tumor Targeting in Photodynamic Therapy.

PubMed

Li, Wenjing; Tan, Sihai; Xing, Yutong; Liu, Qian; Li, Shuang; Chen, Qingle; Yu, Min; Wang, Fengwei; Hong, Zhangyong

2018-04-02

Pyropheophorbide-a (Pyro) is a highly promising photosensitizer for tumor photodynamic therapy (PDT), although its very limited tumor-accumulation ability seriously restricts its clinical applications. A higher accumulation of photosensitizers is very important for the treatment of deeply seated and larger tumors. The conjugation of Pyro with tumor-homing peptide ligands could be a very useful strategy to optimize the physical properties of Pyro. Herein, we reported our studies on the conjugation of Pyro with a cyclic cRGDfK (cRGD) peptide, an integrin binding sequence, to develop highly tumor-specific photosensitizers for PDT application. To further reduce the nonspecific uptake and, thus, reduce the background distribution of the conjugates in normal tissues, we opted to add a highly hydrophilic polyethylene glycol (PEG) chain and an extra strongly hydrophilic carboxylic acid group as the linker to avoid the direct connection of the strongly hydrophobic Pyro macrocycle and cRGD ligand. We reported here the synthesis and characterization of these conjugates, and the influence of the hydrophilic modification on the biological function of the conjugates was carefully studied. The tumor-accumulation ability and photodynamic-induced cell-killing ability of these conjugates were evaluated through both in vitro cell-based experiment and in vivo distribution and tumor therapy experiments with tumor-bearing mice. Thus, the synthesized conjugate significantly improved the tumor enrichment and tumor selectivity of Pyro, as well as abolished the xenograft tumors in the murine model through a one-time PDT treatment.

SU-E-J-16: Automatic Image Contrast Enhancement Based On Automatic Parameter Optimization for Radiation Therapy Setup Verification

DOE Office of Scientific and Technical Information (OSTI.GOV)

Qiu, J; Washington University in St Louis, St Louis, MO; Li, H. Harlod

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 mostmore » 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.« less

Dyslipidemias and Cardiovascular Prevention: Tailoring Treatment According to Lipid Phenotype.

PubMed

Sanin, Veronika; Pfetsch, Vanessa; Koenig, Wolfgang

2017-07-01

This study aimed to present the current information on the genetic background of dyslipidemias and provide insights into the complex pathophysiological role of several plasma lipids/lipoproteins in the pathogenesis of atherosclerotic cardiovascular disease. Furthermore, we aim to summarize established therapies and describe the scientific rationale for the development of novel therapeutic strategies. Evidence from genetic studies suggests that besides lowering low-density lipoprotein cholesterol, pharmacological reduction of triglyceride-rich lipoproteins, or lipoprotein(a) will reduce risk for coronary heart disease. Dyslipidemia, in particular hypercholesterolemia, is a common clinical condition and represents an important determinant of atherosclerotic vascular disease. Treatment decisions are currently guided by the causative lipid phenotype and the presence of other risk factors suggesting a very high cardiovascular risk. Therefore, the identification of lipid disorders and the optimal combination of therapeutic strategies provide an outstanding opportunity for reducing the onset and burden of cardiovascular disease.

Evidence-based periodontal therapy: An overview

PubMed Central

Vijayalakshmi, R.; Anitha, V.; Ramakrishnan, T.; Sudhakar, Uma

2008-01-01

Dentists need to make clinical decisions based on limited scientific evidence. In clinical practice, a clinician must weigh a myriad of evidences every day. The goal of evidence-based dentistry is to help practitioners provide their patients with optimal care. This is achieved by integrating sound research evidence with personal clinical expertise and patient values to determine the best course of treatment. Periodontology has a rich background of research and scholarship. Therefore, efficient use of this wealth of research data needs to be a part of periodontal practice. Evidence-based periodontology aims to facilitate such an approach and it offers a bridge from science to clinical practice. The clinician must integrate the evidence with patient preference, scientific knowledge, and personal experience. Most important, it allows us to care for our patients. Therefore, evidence-based periodontology is a tool to support decision-making and integrating the best evidence available with clinical practice. PMID:20142947

Guidelines for cognitive behavioral training within doctoral psychology programs in the United States: report of the Inter-organizational Task Force on Cognitive and Behavioral Psychology Doctoral Education.

PubMed

Klepac, Robert K; Ronan, George F; Andrasik, Frank; Arnold, Kevin D; Belar, Cynthia D; Berry, Sharon L; Christofff, Karen A; Craighead, Linda W; Dougher, Michael J; Dowd, E Thomas; Herbert, James D; McFarr, Lynn M; Rizvi, Shireen L; Sauer, Eric M; Strauman, Timothy J

2012-12-01

The Association for Behavioral and Cognitive Therapies initiated an interorganizational task force to develop guidelines for integrated education and training in cognitive and behavioral psychology at the doctoral level in the United States. Fifteen task force members representing 16 professional associations participated in a year-long series of conferences, and developed a consensus on optimal doctoral education and training in cognitive and behavioral psychology. The recommendations assume solid foundational training that is typical within applied psychology areas such as clinical and counseling psychology programs located in the United States. This article details the background, assumptions, and resulting recommendations specific to doctoral education and training in cognitive and behavioral psychology, including competencies expected in the areas of ethics, research, and practice. Copyright © 2012. Published by Elsevier Ltd.

Madelung's Disease: Lipectomy or Liposuction?

PubMed Central

Chen, Chun-Ye; Fang, Qing-Qing; Wang, Xiao-Feng; Zhang, Min-Xia; Zhao, Wan-Yi; Shi, Bang-Hui; Wu, Li-Hong; Zhang, Li-Yun

2018-01-01

Background Madelung's disease is a rare lipid metabolic disorder characterized by diffuse, uncapsulated lipomas in the neck, shoulder, and other areas. It mainly affects middle-aged men and is related to alcohol abuse, and the cause is not clear. Surgical treatments include lipectomy and liposuction. Methods This systematic review analyzed the treatment of Madelung's disease described in 52 articles including complete patient details, published between 2000 and 2015, and retrieved from the Web of Science, PubMed, Medline, and Embase. Results Lipectomy was performed in most cases and achieved more complete removal and better control of iatrogenic lesions of nearby structures than liposuction. Liposuction achieved good cosmetic results and is simpler and less invasive than lipectomy, but clinical experience is limited. Conclusions Both lipectomy and liposuction have advantages and drawbacks. Surgeons should base the choice of optimal treatment on patient characteristics. Novel surgical techniques and etiologically targeted treatments hold promise as future therapies. PMID:29682541

Interactive visuo-motor therapy system for stroke rehabilitation.

PubMed

Eng, Kynan; Siekierka, Ewa; Pyk, Pawel; Chevrier, Edith; Hauser, Yves; Cameirao, Monica; Holper, Lisa; Hägni, Karin; Zimmerli, Lukas; Duff, Armin; Schuster, Corina; Bassetti, Claudio; Verschure, Paul; Kiper, Daniel

2007-09-01

We present a virtual reality (VR)-based motor neurorehabilitation system for stroke patients with upper limb paresis. It is based on two hypotheses: (1) observed actions correlated with self-generated or intended actions engage cortical motor observation, planning and execution areas ("mirror neurons"); (2) activation in damaged parts of motor cortex can be enhanced by viewing mirrored movements of non-paretic limbs. We postulate that our approach, applied during the acute post-stroke phase, facilitates motor re-learning and improves functional recovery. The patient controls a first-person view of virtual arms in tasks varying from simple (hitting objects) to complex (grasping and moving objects). The therapist adjusts weighting factors in the non-paretic limb to move the paretic virtual limb, thereby stimulating the mirror neuron system and optimizing patient motivation through graded task success. We present the system's neuroscientific background, technical details and preliminary results.

Management of Docetaxel Failures in Metastatic Castrate-Resistant Prostate Cancer

PubMed Central

Pal, Sumanta K.; Lewis, Brian; Sartor, Oliver

2013-01-01

SYNOPSIS The treatment of metastatic castration resistant prostate cancer (mCRPC) has evolved markedly since the approval of docetaxel-based therapy in 2004. Since that time, 3 distinct agents have gained approval for use in the mCRPC setting, namely sipuleucel-T, cabazitaxel and abiraterone. Even more recently, phase III trials have demonstrated a survival benefit in association with the agents MDV-3100 and radium-223, and FDA approval is anticipated for both of these agents. Although these changes undoubtedly represent progress for the patient with mCRPC, for the practicing physician there is the additional challenge of determining the optimal sequencing for each of these agents. This dilemma is particularly relevant to the post-docetaxel setting, where the indication for several of these agents overlap. Herein, we provide the physician with detailed background on the efficacy and safety of these agents so as to provide a framework for their use in the clinic. PMID:23084533

SU-E-T-182: Feasibility of Dose Painting by Numbers in Proton Therapy with Contour-Driven Plan Optimization

DOE Office of Scientific and Technical Information (OSTI.GOV)

Montero, A Barragan; Differding, S; Lee, J

Purpose: The work aims to 1) prove the feasibility of dose painting by numbers (DPBN) in proton therapy with usual contour-driven plan optimization and 2) compare the achieved plan quality to that of rotational IMRT. Methods: For two patients with head and neck cancers, voxel-by-voxel prescription to the target volume (PTV-PET) was calculated from {sup 18} FDG-PET images and converted to contour-based prescription by defining several sub-contours. Treatments were planned with RayStation (RaySearch Laboratories, Sweden) and proton pencil beam scanning modality. In order to determine the optimal plan parameters to approach the DPBN prescription, the effect of the number ofmore » fields, number of sub-contours and use of range shifter were tested separately on each patient. The number of sub-contours were increased from 3 to 11 while the number of fields were set to 3, 5, 7 and 9. Treatment plans were also optimized on two rotational IMRT systems (TomoTherapy and Varian RapidArc) using previously published guidelines. Results: For both patients, more than 99% of the PTV-PET received at least 95% of the prescribed dose while less than 1% of the PTV-PET received more than 105%, which demonstrates the feasibility of the treatment. Neither the use of a range shifter nor the increase of the number of fields had a significant influence on PTV coverage. Plan quality increased when increasing number of fields up to 7 or 9 and slightly decreased for a bigger number of sub-contours. Good OAR sparing is achieved while keeping high plan quality. Finally, proton therapy achieved significantly better plan quality than rotational IMRT. Conclusion: Voxel-by-voxel prescriptions can be approximated accurately in proton therapy using a contour-driven optimization. Target coverage is nearly insensitive to the number of fields and the use of a range shifter. Finally, plan quality assessment confirmed the superiority of proton therapy compared to rotational IMRT.« less

A fast optimization algorithm for multicriteria intensity modulated proton therapy planning.

PubMed

Chen, Wei; Craft, David; Madden, Thomas M; Zhang, Kewu; Kooy, Hanne M; Herman, Gabor T

2010-09-01

To describe a fast projection algorithm for optimizing intensity modulated proton therapy (IMPT) plans and to describe and demonstrate the use of this algorithm in multicriteria IMPT planning. The authors develop a projection-based solver for a class of convex optimization problems and apply it to IMPT treatment planning. The speed of the solver permits its use in multicriteria optimization, where several optimizations are performed which span the space of possible treatment plans. The authors describe a plan database generation procedure which is customized to the requirements of the solver. The optimality precision of the solver can be specified by the user. The authors apply the algorithm to three clinical cases: A pancreas case, an esophagus case, and a tumor along the rib cage case. Detailed analysis of the pancreas case shows that the algorithm is orders of magnitude faster than industry-standard general purpose algorithms (MOSEK'S interior point optimizer, primal simplex optimizer, and dual simplex optimizer). Additionally, the projection solver has almost no memory overhead. The speed and guaranteed accuracy of the algorithm make it suitable for use in multicriteria treatment planning, which requires the computation of several diverse treatment plans. Additionally, given the low memory overhead of the algorithm, the method can be extended to include multiple geometric instances and proton range possibilities, for robust optimization.

The impact of Asian American value systems on palliative care: illustrative cases from the family-focused grief therapy trial.

PubMed

Mondia, Stephen; Hichenberg, Shira; Kerr, Erica; Eisenberg, Megan; Kissane, David W

2012-09-01

Clinicians meet people from different ethnic backgrounds, yet need to respond in culturally sensitive ways. This article focuses on Asian American families. Within a randomized controlled trial of family therapy commenced during palliative care and continued into bereavement, 3 families of Asian American background were examined qualitatively from a cultural perspective by listening to recordings of 26 therapy sessions and reviewing detailed supervision notes compiled by each therapist. A synopsis of each family's therapy narrative is presented. Prominent themes include family closeness, respect for hierarchy within the family, gender-determined roles, intergenerational tensions, preoccupation with shame and limited emotional expressiveness. Family therapists working with culturally diverse families need to pay thoughtful attention to ethnic issues as they strive to support them during palliative care and bereavement.

[Ego-state Therapy: Psychotherapy for Multiple Personality Disorders].

PubMed

Sugiyama, Toshiro

2018-01-01

The author describes ego-state therapy. This psychotherapy is used for treating multiple personality disorders. The author mentions the theoretical background of this method, and practical points. Initially, ego-state therapy was developed as a type of hypnotherapy, but it evolved as a safe therapeutic method in combination with trauma processing therapies. The author presents a case study, and discusses the clinical significance of this treatment.

Application of Feedback System Control Optimization Technique in Combined Use of Dual Antiplatelet Therapy and Herbal Medicines

PubMed Central

Liu, Wang; Li, Yu-Long; Feng, Mu-Ting; Zhao, Yu-Wei; Ding, Xianting; He, Ben; Liu, Xuan

2018-01-01

Aim: Combined use of herbal medicines in patients underwent dual antiplatelet therapy (DAPT) might cause bleeding or thrombosis because herbal medicines with anti-platelet activities may exhibit interactions with DAPT. In this study, we tried to use a feedback system control (FSC) optimization technique to optimize dose strategy and clarify possible interactions in combined use of DAPT and herbal medicines. Methods: Herbal medicines with reported anti-platelet activities were selected by searching related references in Pubmed. Experimental anti-platelet activities of representative compounds originated from these herbal medicines were investigated using in vitro assay, namely ADP-induced aggregation of rat platelet-rich-plasma. FSC scheme hybridized artificial intelligence calculation and bench experiments to iteratively optimize 4-drug combination and 2-drug combination from these drug candidates. Results: Totally 68 herbal medicines were reported to have anti-platelet activities. In the present study, 7 representative compounds from these herbal medicines were selected to study combinatorial drug optimization together with DAPT, i.e., aspirin and ticagrelor. FSC technique first down-selected 9 drug candidates to the most significant 5 drugs. Then, FSC further secured 4 drugs in the optimal combination, including aspirin, ticagrelor, ferulic acid from DangGui, and forskolin from MaoHouQiaoRuiHua. Finally, FSC quantitatively estimated the possible interactions between aspirin:ticagrelor, aspirin:ferulic acid, ticagrelor:forskolin, and ferulic acid:forskolin. The estimation was further verified by experimentally determined Combination Index (CI) values. Conclusion: Results of the present study suggested that FSC optimization technique could be used in optimization of anti-platelet drug combinations and might be helpful in designing personal anti-platelet therapy strategy. Furthermore, FSC analysis could also identify interactions between different drugs which might provide useful information for research of signal cascades in platelet. PMID:29780330

Maximizing the probability of satisfying the clinical goals in radiation therapy treatment planning under setup uncertainty

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fredriksson, Albin, E-mail: albin.fredriksson@raysearchlabs.com; Hårdemark, Björn; Forsgren, Anders

2015-07-15

Purpose: This paper introduces a method that maximizes the probability of satisfying the clinical goals in intensity-modulated radiation therapy treatments subject to setup uncertainty. Methods: The authors perform robust optimization in which the clinical goals are constrained to be satisfied whenever the setup error falls within an uncertainty set. The shape of the uncertainty set is included as a variable in the optimization. The goal of the optimization is to modify the shape of the uncertainty set in order to maximize the probability that the setup error will fall within the modified set. Because the constraints enforce the clinical goalsmore » to be satisfied under all setup errors within the uncertainty set, this is equivalent to maximizing the probability of satisfying the clinical goals. This type of robust optimization is studied with respect to photon and proton therapy applied to a prostate case and compared to robust optimization using an a priori defined uncertainty set. Results: Slight reductions of the uncertainty sets resulted in plans that satisfied a larger number of clinical goals than optimization with respect to a priori defined uncertainty sets, both within the reduced uncertainty sets and within the a priori, nonreduced, uncertainty sets. For the prostate case, the plans taking reduced uncertainty sets into account satisfied 1.4 (photons) and 1.5 (protons) times as many clinical goals over the scenarios as the method taking a priori uncertainty sets into account. Conclusions: Reducing the uncertainty sets enabled the optimization to find better solutions with respect to the errors within the reduced as well as the nonreduced uncertainty sets and thereby achieve higher probability of satisfying the clinical goals. This shows that asking for a little less in the optimization sometimes leads to better overall plan quality.« less

Breast Cancer Subtypes: Morphologic and Biologic Characterization

PubMed Central

2016-01-01

Advances in basic science, technology and translational research have created a revolution in breast cancer diagnosis and therapy. Researchers' discoveries of genes defining variability in response to therapy and heterogeneity in clinical presentations and tumor biology are the foundation of the path to personalized medicine. The success of personalized breast cancer care depends on access to pertinent clinical information and risk factors, optimal imaging findings, well-established morphologic features, and traditional and contemporary prognostic/predictive testing. The integration of these entities provides an opportunity to identify patients who can benefit from specific therapies, and demonstrates the link between breast cancer subtypes and their association with different tumor biology. It is critical to recognize specific types of breast cancer in individual patients and design optimal personalized therapy. This article will highlight the roles of morphologic features and established tumor biomarkers on patient outcome. PMID:26756229

Optimal temperature control of tissue embedded with gold nanoparticles for enhanced thermal therapy based on two-energy equation model.

PubMed

Wang, Shen-Ling; Qi, Hong; Ren, Ya-Tao; Chen, Qin; Ruan, Li-Ming

2018-05-01

Thermal therapy is a very promising method for cancer treatment, which can be combined with chemotherapy, radiotherapy and other programs for enhanced cancer treatment. In order to get a better effect of thermal therapy in clinical applications, optimal internal temperature distribution of the tissue embedded with gold nanoparticles (GNPs) for enhanced thermal therapy was investigated in present research. The Monte Carlo method was applied to calculate the heat generation of the tissue embedded with GNPs irradiated by continuous laser. To have a better insight into the physical problem of heat transfer in tissues, the two-energy equation was employed to calculate the temperature distribution of the tissue in the process of GNPs enhanced therapy. The Arrhenius equation was applied to evaluate the degree of permanent thermal damage. A parametric study was performed to investigate the influence factors on the tissue internal temperature distribution, such as incident light intensity, the GNPs volume fraction, the periodic heating and cooling time, and the incident light position. It was found that period heating and cooling strategy can effectively avoid overheating of skin surface and heat damage of healthy tissue. Lower GNPs volume fraction will be better for the heat source distribution. Furthermore, the ring heating strategy is superior to the central heating strategy in the treatment effect. All the analysis provides theoretical guidance for optimal temperature control of tissue embedded with GNP for enhanced thermal therapy. Copyright © 2018 Elsevier Ltd. All rights reserved.

Optimization of personalized therapies for anticancer treatment.

PubMed

Vazquez, Alexei

2013-04-12

As today, there are hundreds of targeted therapies for the treatment of cancer, many of which have companion biomarkers that are in use to inform treatment decisions. If we would consider this whole arsenal of targeted therapies as a treatment option for every patient, very soon we will reach a scenario where each patient is positive for several markers suggesting their treatment with several targeted therapies. Given the documented side effects of anticancer drugs, it is clear that such a strategy is unfeasible. Here, we propose a strategy that optimizes the design of combinatorial therapies to achieve the best response rates with the minimal toxicity. In this methodology markers are assigned to drugs such that we achieve a high overall response rate while using personalized combinations of minimal size. We tested this methodology in an in silico cancer patient cohort, constructed from in vitro data for 714 cell lines and 138 drugs reported by the Sanger Institute. Our analysis indicates that, even in the context of personalized medicine, combinations of three or more drugs are required to achieve high response rates. Furthermore, patient-to-patient variations in pharmacokinetics have a significant impact in the overall response rate. A 10 fold increase in the pharmacokinetics variations resulted in a significant drop the overall response rate. The design of optimal combinatorial therapy for anticancer treatment requires a transition from the one-drug/one-biomarker approach to global strategies that simultaneously assign makers to a catalog of drugs. The methodology reported here provides a framework to achieve this transition.

Should psychology be 'positive'? Letting the philosophers speak: Commentary on... Hope, optimism and delusion.

PubMed

Oyebode, Femi

2014-04-01

This is a brief commentary on the value of optimism in therapy. It draws on the philosophical writings of Schopenhauer and Aristotle. It suggests that the modern preoccupation with optimism may be as extreme as the bleak pessimistic outlook favoured by Schopenhauer.

Cyclic cidofovir (cHPMPC) prevents congenital cytomegalovirus infection in a guinea pig model

PubMed Central

Schleiss, Mark R; Anderson, Jodi L; McGregor, Alistair

2006-01-01

Background Congenital cytomegalovirus (CMV) infection is a major public health problem. Antiviral therapies administered during pregnancy might prevent vertical CMV transmission and disease in newborns, but these agents have not been evaluated in clinical trials. The guinea pig model of congenital CMV infection was therefore used to test the hypothesis that antiviral therapy, using the agent agent cyclic cidofovir (cHPMPC), could prevent congenital CMV infection. Results Pregnant outbred Hartley guinea pigs were challenged in the early-third trimester with guinea pig CMV (GPCMV) and treated with placebo, or the antiviral agent, cyclic cidofovir. To optimize detection of vertical infection, an enhanced green fluorescent protein (eGFP)-tagged virus was employed. Compared to placebo, cyclic cidofovir-treated dams and pups had reduced mortality following GPCMV challenge. The magnitude of GPCMV-induced maternal and fetal mortality in this study was reduced from 5/25 animals in the placebo group to 0/21 animals in the treatment group (p = 0.05, Fisher's exact test). By viral culture assay, antiviral therapy was found to completely prevent GPCMV transmission to the fetus. In control pups, 5/19 (26%) were culture-positive for GPCMV, compared to 0/16 of pups in the cyclic cidofovir treatment group (p < 0.05, Fisher's exact test). Conclusion Antiviral therapy with cyclic cidofovir improves pregnancy outcomes in guinea pigs, and eliminates congenital CMV infection, following viral challenge in the third trimester. This study also demonstrated that an eGFP-tagged recombinant virus, with the reporter gene inserted into a dispensable region of the viral genome, retained virulence, including the potential for congenital transmission, facilitating tissue culture-based detection of congenital infection. These observations provide support for clinical trials of antivirals for reduction of congenital CMV infection. PMID:16509982

Cancer and orofacial pain

PubMed Central

Salvemini, Daniela

2016-01-01

Background Cancer pain is a devastating condition. Pain in the orofacial region, may be present as the single symptom of cancer or as a symptom of cancer in its later stages. This manuscript revises in a comprehensive manner the content of the conference entitled “Orofacial Pain and Cancer” (Dolor Orofacial y Cancer) given at the VI Simposio International “Advances in Oral Cancer” on the 22 July, 2016 in Donostia. Material and Methods We have reviewed (pubmed-medline) from the most relevant literature including reviews, systematic reviews and clinical cases, the significant and evidence-based mechanisms and mediators of cancer-associated facial pain, the diverse types of cancers that can be present in the craniofacial region locally or from distant sites that can refer to the orofacial region, cancer therapy that may induce pain in the orofacial region as well as discussed some of the new advancements in cancer pain therapy. Results There is still a lack of understanding of cancer pain pathophysiology since depends of the intrinsic heterogeneity, type and anatomic location that the cancer may present, making more challenging the creation of better therapeutic options. Orofacial pain can arise from regional or distant tumor effects or as a consequence of cancer therapy. Conclusions The clinician needs to be aware that the pain may present the characteristics of any other orofacial pain disorder so a careful differential diagnosis needs to be given. Cancer pain diagnosis is made by exclusion and only can be reached after a thorough medical history, and all the common etiologies have been carefully investigated and ruled out. The current management tools are not optimal but there is hope for new, safer and effective therapies coming in the next years. Key words:Pain, orofacial, facial, cancer. PMID:27694791

Functional Medicine Approach to Traumatic Brain Injury.

PubMed

Richer, Alice C

2017-08-01

Background: The U.S. military has seen dramatic increases in traumatic brain injuries (TBIs) among military personnel due to the nature of modern-day conflicts. Conventional TBI treatment for secondary brain injuries has suboptimal success rates, and patients, families, and healthcare professionals are increasingly turning to alternative medicine treatments. Objective: Effective treatments for the secondary injury cascades that occur after an initial brain trauma are unclear at this time. The goal of successful treatment options for secondary TBI injuries is to reduce oxidative stress, excitotoxicity, and inflammation while supporting mitochondrial functions and repair of membranes, synapses, and axons. Intervention: A new paradigm of medical care, known as functional medicine, is increasing in popularity and acceptance. Functional medicine combines conventional treatment methods with complementary, genetic, holistic, and nutritional therapies. The approach is to assess the patient as a whole person, taking into account the interconnectedness of the body and its unique reaction to disease, injury, and illness while working to restore balance and optimal health. Functional medicine treatment recommendations often include the use of acupuncture, Ayurveda, chiropractic manipulation, detoxification programs, herbal and homeopathic supplements, specialized diets, massage, meditation and mindfulness practices, neurobiofeedback, nutritional supplements, t'ai chi , and yoga. At present, some of these alternative treatments appear to be beneficial, but more research is needed to validate reported outcomes. Conclusions: Few clinical studies validate the effectiveness of alternative therapies for TBIs. However, further clinical trials and empirical studies warrant further investigation based on some reported positive results from research studies, case histories, anecdotal evidence, and widespread popularity of some approaches. To date, only nutritional therapies and hyperbaric oxygen therapy have shown the most promise and potential for improved outcomes for the treatment of secondary TBI injuries.

Collaborative Pediatric Bone Tumor Program to Improve Access to Specialized Care: An Initiative by the Lebanese Children’s Oncology Group

PubMed Central

Merabi, Zeina; Abboud, Miguel R.; Muwakkit, Samar; Noun, Peter; Gemayel, Gladys; Bechara, Elie; Khalifeh, Hassan; Farah, Roula; Kabbara, Nabil; El-Khoury, Tarek; Al-Yousef, Rasha; Haidar, Rachid; Saghieh, Said; Eid, Toufic; Akel, Samir; Khoury, Nabil; Bayram, Layal; Krasin, Matthew J.; Jeha, Sima; El-Solh, Hassan

2017-01-01

Background Children with malignant bone tumors have average 5-year survival rates of 60% to 70% with current multimodality therapy. Local control modalities aimed at preserving function greatly influence the quality of life of long-term survivors. In developing countries, the limited availability of multidisciplinary care and limited expertise in specialized surgery and pediatric radiation therapy, as well as financial cost, all form barriers to achieving optimal outcomes in this population. Methods We describe the establishment of a collaborative pediatric bone tumor program among a group of pediatric oncologists in Lebanon and Syria. This program provides access to specialized local control at a tertiary children’s cancer center to pediatric patients with newly diagnosed bone tumors at participating sites. Central review of pathology, staging, and treatment planning is performed in a multidisciplinary tumor board setting. Patients receive chemotherapy at their respective centers on a unified treatment plan. Surgery and/or radiation therapy are performed centrally by specialized staff at the children’s cancer center. Cost barriers were resolved through a program development initiative led by St Jude Children’s Research Hospital. Once program feasibility was achieved, the Children’s Cancer Center of Lebanon Foundation, via fundraising efforts, provided continuation of program-directed funding. Results Findings over a 3-year period showed the feasibility of this project, with timely local control and protocol adherence at eight collaborating centers. We report success in providing standard-of-care multidisciplinary therapy to this patient population with complex needs and financially challenging surgical procedures. Conclusion This initiative can serve as a model, noting that facilitating access to specialized multidisciplinary care, resolution of financial barriers, and close administrative coordination all greatly contributed to the success of the program. PMID:28717738

Functional Medicine Approach to Traumatic Brain Injury

PubMed Central

2017-01-01

Abstract Background: The U.S. military has seen dramatic increases in traumatic brain injuries (TBIs) among military personnel due to the nature of modern-day conflicts. Conventional TBI treatment for secondary brain injuries has suboptimal success rates, and patients, families, and healthcare professionals are increasingly turning to alternative medicine treatments. Objective: Effective treatments for the secondary injury cascades that occur after an initial brain trauma are unclear at this time. The goal of successful treatment options for secondary TBI injuries is to reduce oxidative stress, excitotoxicity, and inflammation while supporting mitochondrial functions and repair of membranes, synapses, and axons. Intervention: A new paradigm of medical care, known as functional medicine, is increasing in popularity and acceptance. Functional medicine combines conventional treatment methods with complementary, genetic, holistic, and nutritional therapies. The approach is to assess the patient as a whole person, taking into account the interconnectedness of the body and its unique reaction to disease, injury, and illness while working to restore balance and optimal health. Functional medicine treatment recommendations often include the use of acupuncture, Ayurveda, chiropractic manipulation, detoxification programs, herbal and homeopathic supplements, specialized diets, massage, meditation and mindfulness practices, neurobiofeedback, nutritional supplements, t'ai chi, and yoga. At present, some of these alternative treatments appear to be beneficial, but more research is needed to validate reported outcomes. Conclusions: Few clinical studies validate the effectiveness of alternative therapies for TBIs. However, further clinical trials and empirical studies warrant further investigation based on some reported positive results from research studies, case histories, anecdotal evidence, and widespread popularity of some approaches. To date, only nutritional therapies and hyperbaric oxygen therapy have shown the most promise and potential for improved outcomes for the treatment of secondary TBI injuries. PMID:28874921

Antithrombotic Therapy in Neonates and Children

PubMed Central

Monagle, Paul; Chan, Anthony K. C.; Goldenberg, Neil A.; Ichord, Rebecca N.; Journeycake, Janna M.; Nowak-Göttl, Ulrike

2012-01-01

Background: Neonates and children differ from adults in physiology, pharmacologic responses to drugs, epidemiology, and long-term consequences of thrombosis. This guideline addresses optimal strategies for the management of thrombosis in neonates and children. Methods: The methods of this guideline follow those described in the Methodology for the Development of Antithrombotic Therapy and Prevention of Thrombosis Guidelines: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Results: We suggest that where possible, pediatric hematologists with experience in thromboembolism manage pediatric patients with thromboembolism (Grade 2C). When this is not possible, we suggest a combination of a neonatologist/pediatrician and adult hematologist supported by consultation with an experienced pediatric hematologist (Grade 2C). We suggest that therapeutic unfractionated heparin in children is titrated to achieve a target anti-Xa range of 0.35 to 0.7 units/mL or an activated partial thromboplastin time range that correlates to this anti-Xa range or to a protamine titration range of 0.2 to 0.4 units/mL (Grade 2C). For neonates and children receiving either daily or bid therapeutic low-molecular-weight heparin, we suggest that the drug be monitored to a target range of 0.5 to 1.0 units/mL in a sample taken 4 to 6 h after subcutaneous injection or, alternatively, 0.5 to 0.8 units/mL in a sample taken 2 to 6 h after subcutaneous injection (Grade 2C). Conclusions: The evidence supporting most recommendations for antithrombotic therapy in neonates and children remains weak. Studies addressing appropriate drug target ranges and monitoring requirements are urgently required in addition to site- and clinical situation-specific thrombosis management strategies. PMID:22315277

A new combined strategy to implement a community occupational therapy intervention: designing a cluster randomized controlled trial

PubMed Central

2011-01-01

Background Even effective interventions for people with dementia and their caregivers require specific implementation efforts. A pilot study showed that the highly effective community occupational therapy in dementia (COTiD) program was not implemented optimally due to various barriers. To decrease these barriers and make implementation of the program more effective a combined implementation (CI) strategy was developed. In our study we will compare the effectiveness of this CI strategy with the usual educational (ED) strategy. Methods In this cluster randomized, single-blinded, controlled trial, each cluster consists of at least two occupational therapists, a manager, and a physician working at Dutch healthcare organizations that deliver community occupational therapy. Forty-five clusters, stratified by healthcare setting (nursing home, hospital, mental health service), have been allocated randomly to either the intervention group (CI strategy) or the control group (ED strategy). The study population consists of the professionals included in each cluster and community-dwelling people with dementia and their caregivers. The primary outcome measures are the use of community OT, the adherence of OTs to the COTiD program, and the cost effectiveness of implementing the COTiD program in outpatient care. Secondary outcome measures are patient and caregiver outcomes and knowledge of managers, physicians and OTs about the COTiD program. Discussion Implementation research is fairly new in the field of occupational therapy, making this a unique study. This study does not only evaluate the effects of the CI-strategy on professionals, but also the effects of professionals' degree of implementation on client and caregiver outcomes. Clinical trials registration NCT01117285 PMID:21450063

Key articles and guidelines in the management of pulmonary arterial hypertension: 2011 update.

PubMed

Johnson, Samuel G; Kayser, Steven R; Attridge, Rebecca L; Duvall, Laura; Kiser, Tyree H; Moote, Rebecca; Reed, Brent N; Rodgers, Jo E; Erstad, Brian

2012-06-01

Pharmacotherapeutic approaches for the management of pulmonary arterial hypertension (PAH) have expanded greatly in the last 10 years. Pulmonary arterial hypertension is a relatively rare disease and is associated with myriad disease processes. The older term for PAH, primary PAH, has been changed to represent these differences and to distinguish it from postcapillary PAH associated with left-sided heart failure. Limitations in evaluating treatment approaches for PAH include its rarity, the small number of patients included in clinical trials, and issues regarding the use of placebo-controlled trials in a disease with such a high mortality rate if left untreated. Management options include the use of prostacyclin and prostacyclin analogues, endothelin receptor antagonists, and phosphodiesterase inhibitors, as well as traditional background therapy with diuretics, digoxin, calcium channel blockers, and warfarin. Numerous drugs are under investigation to evaluate their possible roles in management. Combination therapy is increasingly becoming a standard approach to therapy, with mounting literature to document effectiveness. Current or emerging roles for the pharmacist in the management of PAH largely involves ensuring access to drug therapy, facilitating specialty pharmacy dispensing, and providing patient counseling. Newer roles may include future drug development, optimized use of investigational drugs, and specialized disease management programs. This compilation includes a series of articles identifying important literature in cardiovascular pharmacotherapy. This bibliography focuses on pharmacotherapeutic management of pulmonary arterial hypertension (PAH). Most of the cited works present the results of significant human clinical studies that have shaped the management of patients with PAH. Limited primary literature is available for some topics, so in addition, consensus documents prepared by expert panels are reviewed. This compilation may serve as a teaching tool, reference resource, or update of the literature for pharmacy clinicians, physicians, and students. © 2012 Pharmacotherapy Publications, Inc.

Conception of a New Recoil Proton Telescope for Real-Time Neutron Spectrometry in Proton-Therapy

NASA Astrophysics Data System (ADS)

Combe, Rodolphe; Arbor, Nicolas; el Bitar, Ziad; Higueret, Stéphane; Husson, Daniel

2018-01-01

Neutrons are the main type of secondary particles emitted in proton-therapy. Because of the risk of secondary cancer and other late occurring effects, the neutron dose should be included in the out-of-field dose calculations. A neutron spectrometer has to be used to take into account the energy dependence of the neutron radiological weighting factor. Due to its high dependence on various parameters of the irradiation (beam, accelerator, patient), the neutron spectrum should be measured independently for each treatment. The current reference method for the measurement of the neutron energy, the Bonner Sphere System, consists of several homogeneous polyethylene spheres with increasing diameters equipped with a proportional counter. It provides a highresolution reconstruction of the neutron spectrum but requires a time-consuming work of signal deconvolution. New neutron spectrometers are being developed, but the main experimental limitation remains the high neutron flux in proton therapy treatment rooms. A new model of a real-time neutron spectrometer, based on a Recoil Proton Telescope technology, has been developed at the IPHC. It enables a real-time high-rate reconstruction of the neutron spectrum from the measurement of the recoil proton trajectory and energy. A new fast-readout microelectronic integrated sensor, called FastPixN, has been developed for this specific purpose. A first prototype, able to detect neutrons between 5 and 20 MeV, has already been validated for metrology with the AMANDE facility at Cadarache. The geometry of the new Recoil Proton Telescope has been optimized via extensive Geant4 Monte Carlo simulations. Uncertainty sources have been carefully studied in order to improve simultaneously efficiency and energy resolution, and solutions have been found to suppress the various expected backgrounds. We are currently upgrading the prototype for secondary neutron detection in proton therapy applications.

SU-F-J-133: Adaptive Radiation Therapy with a Four-Dimensional Dose Calculation Algorithm That Optimizes Dose Distribution Considering Breathing Motion

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ali, I; Algan, O; Ahmad, S

Purpose: To model patient motion and produce four-dimensional (4D) optimized dose distributions that consider motion-artifacts in the dose calculation during the treatment planning process. Methods: An algorithm for dose calculation is developed where patient motion is considered in dose calculation at the stage of the treatment planning. First, optimal dose distributions are calculated for the stationary target volume where the dose distributions are optimized considering intensity-modulated radiation therapy (IMRT). Second, a convolution-kernel is produced from the best-fitting curve which matches the motion trajectory of the patient. Third, the motion kernel is deconvolved with the initial dose distribution optimized for themore » stationary target to produce a dose distribution that is optimized in four-dimensions. This algorithm is tested with measured doses using a mobile phantom that moves with controlled motion patterns. Results: A motion-optimized dose distribution is obtained from the initial dose distribution of the stationary target by deconvolution with the motion-kernel of the mobile target. This motion-optimized dose distribution is equivalent to that optimized for the stationary target using IMRT. The motion-optimized and measured dose distributions are tested with the gamma index with a passing rate of >95% considering 3% dose-difference and 3mm distance-to-agreement. If the dose delivery per beam takes place over several respiratory cycles, then the spread-out of the dose distributions is only dependent on the motion amplitude and not affected by motion frequency and phase. This algorithm is limited to motion amplitudes that are smaller than the length of the target along the direction of motion. Conclusion: An algorithm is developed to optimize dose in 4D. Besides IMRT that provides optimal dose coverage for a stationary target, it extends dose optimization to 4D considering target motion. This algorithm provides alternative to motion management techniques such as beam-gating or breath-holding and has potential applications in adaptive radiation therapy.« less

The Provision of Psychological Therapy to People with Intellectual Disabilities: An Investigation into Some of the Relevant Factors

ERIC Educational Resources Information Center

Mason, J.

2007-01-01

Background: Five factors are proposed as important in influencing the provision of psychological therapy to people with intellectual disabilities (IDs): the perceived effectiveness of psychological therapy, individual clinician competence, service resources (number of trained clinicians), the level of the clients disability and the diagnostic…

The Experiences of High Intensity Therapists Delivering Cognitive Behavioural Therapy to People with Intellectual Disabilities

ERIC Educational Resources Information Center

Marwood, Hayley; Chinn, Deborah; Gannon, Kenneth; Scior, Katrina

2018-01-01

Background: People with intellectual disabilities (ID) should be able to access the Improving Access to Psychological Therapies (IAPT) programme, currently a main provider of mainstream mental health services in England. IAPT offer cognitive behavioural therapy (CBT) to individuals experiencing mental health problems, although its effectiveness…

Child-Therapist Alliance and Clinical Outcomes in Cognitive Behavioral Therapy for Child Anxiety Disorders

ERIC Educational Resources Information Center

Chiu, Angela W.; McLeod, Bryce D.; Har, Kim; Wood, Jeffrey J.

2009-01-01

Background: Few studies have examined the link between child-therapist alliance and outcome in manual-guided cognitive behavioral therapy (CBT) for children diagnosed with anxiety disorders. This study sought to clarify the nature and strength of this relation. Methods: The Therapy Process Observational Coding System for Child…

Using Repertory Grid Techniques to Measure Change Following Dialectical Behaviour Therapy with Adults with Learning Disabilities: Two Case Studies

ERIC Educational Resources Information Center

McNair, Louisa; Woodrow, Ceri; Hare, Dougal

2016-01-01

Background: Government strategy indicates that individuals with learning disabilities should have access to adapted psychological therapies. Dialectical behaviour therapy (DBT) is recommended for the treatment of borderline personality disorder (BPD); however, there is little published research regarding whether it can be appropriately adapted for…

How do surgeons decide to refer patients for adjuvant cancer treatment? Protocol for a qualitative study

PubMed Central

2012-01-01

Background Non-small cell lung cancer, breast cancer, and colorectal cancer are commonly diagnosed cancers in Canada. Patients diagnosed with early-stage non-small cell lung, breast, or colorectal cancer represent potentially curable populations. For these patients, surgery is the primary mode of treatment, with (neo)adjuvant therapies (e.g., chemotherapy, radiotherapy) recommended according to disease stage. Data from our research in Nova Scotia, as well as others’, demonstrate that a substantial proportion of non-small cell lung cancer and colorectal cancer patients, for whom practice guidelines recommend (neo)adjuvant therapy, are not referred for an oncologist consultation. Conversely, surveillance data and clinical experience suggest that breast cancer patients have much higher referral rates. Since surgery is the primary treatment, the surgeon plays a major role in referring patients to oncologists. Thus, an improved understanding of how surgeons make decisions related to oncology services is important to developing strategies to optimize referral rates. Few studies have examined decision making for (neo)adjuvant therapy from the perspective of the cancer surgeon. This study will use qualitative methods to examine decision-making processes related to referral to oncology services for individuals diagnosed with potentially curable non-small cell lung, breast, or colorectal cancer. Methods A qualitative study will be conducted, guided by the principles of grounded theory. The study design is informed by our ongoing research, as well as a model of access to health services. The method of data collection will be in-depth, semi structured interviews. We will attempt to recruit all lung, breast, and/or colorectal cancer surgeons in Nova Scotia (n ≈ 42), with the aim of interviewing a minimum of 34 surgeons. Interviews will be audiotaped and transcribed verbatim. Data will be collected and analyzed concurrently, with two investigators independently coding and analyzing the data. Analysis will involve an inductive, grounded approach using constant comparative analysis. Discussion The primary outcomes will be (1) identification of the patient, surgeon, institutional, and health-system factors that influence surgeons’ decisions to refer non-small cell lung, breast, and colorectal cancer patients to oncology services when consideration for (neo)adjuvant therapy is recommended and (2) identification of potential strategies that could optimize referral to oncology for appropriate individuals. PMID:23098262

Optimizing biological therapy in Crohn's disease.

PubMed

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.

Patient-centered clinical trials.

PubMed

Chaudhuri, Shomesh E; Ho, Martin P; Irony, Telba; Sheldon, Murray; Lo, Andrew W

2018-02-01

We apply Bayesian decision analysis (BDA) to incorporate patient preferences in the regulatory approval process for new therapies. By assigning weights to type I and type II errors based on patient preferences, the significance level (α) and power (1-β) of a randomized clinical trial (RCT) for a new therapy can be optimized to maximize the value to current and future patients and, consequently, to public health. We find that for weight-loss devices, potentially effective low-risk treatments have optimal αs larger than the traditional one-sided significance level of 5%, whereas potentially less effective and riskier treatments have optimal αs below 5%. Moreover, the optimal RCT design, including trial size, varies with the risk aversion and time-to-access preferences and the medical need of the target population. Copyright © 2017 Elsevier Ltd. All rights reserved.

Inhalation devices: from basic science to practical use, innovative vs generic products.

PubMed

Pirozynski, Michal; Sosnowski, Tomasz R

2016-11-01

Inhalation therapy is a convenient method of treating respiratory diseases. The key factors required for inhalation are the preparation of drug carriers (aerosol particles) allowing reproducible dosing during administration. These technical challenges are accomplished with a variety of inhalation devices (inhalers) and medicinal formulations, which are optimized to be easily converted into inhalable aerosols. Areas covered: This review is focused on the most important, but often overlooked, effects, which are required for the reliable and reproducible inhalable drug administration. The effects of patient-related issues that influence inhalation therapy, such as proper selection of inhalers for specific cases is discussed. We also discuss factors that are the most essential if generic inhalation product should be considered equivalent to the drugs with the clinically confirmed efficacy. Expert opinion: Proper device selection is crucial in clinical results of inhalation therapy. The patients' ability to coordinate inhalation with actuation, generation of optimal flow through the device, use of optimal inspiratory volume, all produces crucial effects on disease control. Also the severity of the disease process effects proper use of inhalers. Interchanging of inhalers can produce potentially conflicting problem regarding efficacy and safety of inhalation therapy.

Antibody-cytokine fusion proteins for treatment of cancer: engineering cytokines for improved efficacy and safety.

PubMed

Young, Patricia A; Morrison, Sherie L; Timmerman, John M

2014-10-01

The true potential of cytokine therapies in cancer treatment is limited by the inability to deliver optimal concentrations into tumor sites due to dose-limiting systemic toxicities. To maximize the efficacy of cytokine therapy, recombinant antibody-cytokine fusion proteins have been constructed by a number of groups to harness the tumor-targeting ability of monoclonal antibodies. The aim is to guide cytokines specifically to tumor sites where they might stimulate more optimal anti-tumor immune responses while avoiding the systemic toxicities of free cytokine therapy. Antibody-cytokine fusion proteins containing interleukin (IL)-2, IL-12, IL-21, tumor necrosis factor (TNF)α, and interferons (IFNs) α, β, and γ have been constructed and have shown anti-tumor activity in preclinical and early-phase clinical studies. Future priorities for development of this technology include optimization of tumor targeting, bioactivity of the fused cytokine, and choice of appropriate agents for combination therapies. This review is intended to serve as a framework for engineering an ideal antibody-cytokine fusion protein, focusing on previously developed constructs and their clinical trial results. Copyright © 2014 Elsevier Inc. All rights reserved.

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

PubMed

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.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Camingue, Pamela; Christian, Rochelle; Ng, Davin

The purpose of this study was to compare 4 different external beam radiation therapy treatment techniques for the treatment of T1-2, N0, M0 glottic cancers: traditional lateral beams with wedges (3D), 5-field intensity-modulated radiation therapy (IMRT), volumetric modulated arc therapy (VMAT), and proton therapy. Treatment plans in each technique were created for 10 patients using consistent planning parameters. The photon treatment plans were optimized using Philips Pinnacle{sub 3} v.9 and the IMRT and VMAT plans used the Direct Machine Parameter Optimization algorithm. The proton treatment plans were optimized using Varian Eclipse Proton v.8.9. The prescription used for each plan wasmore » 63 Gy in 28 fractions. The contours for spinal cord, right carotid artery, left carotid artery, and normal tissue were created with respect to the patient's bony anatomy so that proper comparisons of doses could be made with respect to volume. An example of the different isodose distributions will be shown. The data collection for comparison purposes includes: clinical treatment volume coverage, dose to spinal cord, dose to carotid arteries, and dose to normal tissue. Data comparisons will be displayed graphically showing the maximum, mean, median, and ranges of doses.« less

Mutation testing for directing upfront targeted therapy and post-progression combination therapy strategies in lung adenocarcinoma

PubMed Central

Salgia, Ravi

2016-01-01

ABSTRACT Introduction: Advances in the biology of non-small-cell lung cancer, especially adenocarcinoma, reveal multiple molecular subtypes driving oncogenesis. Accordingly, individualized targeted therapeutics are based on mutational diagnostics. Areas covered: Advances in strategies and techniques for individualized treatment, particularly of adenocarcinoma, are described through literature review. Approved therapies are established for some molecular subsets, with new driver mutations emerging that represent increasing proportions of patients. Actionable mutations are de novo oncogenic drivers or acquired resistance mediators, and mutational profiling is important for directing therapy. Patients should be monitored for emerging actionable resistance mutations. Liquid biopsy and associated multiplex diagnostics will be important means to monitor patients during treatment. Expert commentary: Outcomes with targeted agents may be improved by integrating mutation screens during treatment to optimize subsequent therapy. In order for this to be translated into impactful patient benefit, appropriate platforms and strategies need to be optimized and then implemented universally. PMID:27139190

Low-level laser therapy of acute and chronic pain: results of the trials and light delivery optimization

NASA Astrophysics Data System (ADS)

Stoykova, Elena V.; Roeva, Tatiana

2003-09-01

The work presents the results of the low-level laser therapy (LLLT) of two groups of volunteers with a variety of conditions performed with a GaAs-system. The volunteers were randomly selected among the patients who were usually treated by conventional therapy that included massage and acupuncture needles. The LLLT was proposed to the first group as extension of conventional treatment. The second group underwent only the LLLT. The effectiveness of the therapy was graded under four categories. Short-term and long-term side effects as well as conditions responding only to LLLT were recorded. The successful treatments were up to 70% for both groups, which coincided with the result of the control group treated by the conventional therapy. For optimization of the light delivery, the spatial maps of the absorbed dose in a homogeneous medium, both in the proximity of the light source and at a distance from it, were compared for collimated and divergent light beams using a reduced variance Monte-Carlo code.

Optimal pharmacological therapy in ST-elevation myocardial infarction-a review : A review of antithrombotic therapies in STEMI.

PubMed

Hermanides, R S; Kilic, S; van 't Hof, A W J

2018-04-23

Antithrombotic therapy is an essential component in the optimisation of clinical outcomes in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention. There are currently several intravenous anticoagulant drugs available for primary percutaneous coronary intervention. Dual antiplatelet therapy comprising aspirin and P2Y12 inhibitor represents the cornerstone treatment for STEMI. However, these effective treatment strategies may be associated with bleeding complications. Compared with clopidogrel, prasugrel and ticagrelor are more potent and predictable, which translates into better clinical outcomes. Therefore, these agents are the first-line treatment in primary percutaneous coronary intervention. However, patients can still experience adverse ischaemic events, which might be in part attributed to alternative pathways triggering thrombosis. In this review, we provide a critical and updated review of currently available antithrombotic therapies used in patients with STEMI undergoing primary PCI. Finding a balance that minimises both thrombotic and bleeding risk is difficult, but crucial. Further randomised trials for this optimal balance are needed.

Optimized Delivery System Achieves Enhanced Endomyocardial Stem Cell Retention

PubMed Central

Behfar, Atta; Latere, Jean-Pierre; Bartunek, Jozef; Homsy, Christian; Daro, Dorothee; Crespo-Diaz, Ruben J.; Stalboerger, Paul G.; Steenwinckel, Valerie; Seron, Aymeric; Redfield, Margaret M.; Terzic, Andre

2014-01-01

Background Regenerative cell-based therapies are associated with limited myocardial retention of delivered stem cells. The objective of this study is to develop an endocardial delivery system for enhanced cell retention. Methods and Results Stem cell retention was simulated in silico using one and three-dimensional models of tissue distortion and compliance associated with delivery. Needle designs, predicted to be optimal, were accordingly engineered using nitinol – a nickel and titanium alloy displaying shape memory and super-elasticity. Biocompatibility was tested with human mesenchymal stem cells. Experimental validation was performed with species-matched cells directly delivered into Langendorff-perfused porcine hearts or administered percutaneously into the endocardium of infarcted pigs. Cell retention was quantified by flow cytometry and real time quantitative polymerase chain reaction methodology. Models, computing optimal distribution of distortion calibrated to favor tissue compliance, predicted that a 75°-curved needle featuring small-to-large graded side holes would ensure the highest cell retention profile. In isolated hearts, the nitinol curved needle catheter (C-Cath) design ensured 3-fold superior stem cell retention compared to a standard needle. In the setting of chronic infarction, percutaneous delivery of stem cells with C-Cath yielded a 37.7±7.1% versus 10.0±2.8% retention achieved with a traditional needle, without impact on biocompatibility or safety. Conclusions Modeling guided development of a nitinol-based curved needle delivery system with incremental side holes achieved enhanced myocardial stem cell retention. PMID:24326777

The Associations Between Physical Therapy and Long-Term Outcomes for Individuals with Lumbar Spinal Stenosis in the SPORT study

PubMed Central

Fritz, Julie M.; Lurie, Jon D.; Zhao, Wenyan; Whitman, Julie M.; Delitto, Anthony; Brennan, Gerard P.; Weinstein, James N.

2013-01-01

Background/Context A period of non-surgical management is advocated prior to surgical treatment for most patients with lumbar spinal stenosis. Currently, little evidence is available to define optimal non-surgical management. Physical therapy is often used, however its use and effectiveness relative to other non-surgical strategies has not been adequately explored. Purpose Describe the utilization of physical therapy and other non-surgical interventions by patients with lumbar spinal stenosis and examine the relationship between physical therapy and long-term prognosis. Study Design Secondary analysis of the Spine Patient Outcomes Research Trial (SPORT) combining data from randomized and observational studies. Setting 13 spine clinics in 11 states in the United States. Patient Sample Patients with lumbar spinal stenosis receiving non-surgical management including those who did or did not receive physical therapy within 6 weeks of enrollment. Outcome Measures Primary outcome measures included cross-over to surgery, the bodily pain and physical function scales changes from the Survey Short Form 36 (SF-36), and the modified Oswestry Disability Index. Secondary outcome measures were patient satisfaction and the Sciatica Bothersomeness Index. Methods Baseline characteristics and rates of cross-over to surgery were compared between patients who did or did not receive physical therapy. Baseline factors predictive of receiving physical therapy were examined with logistic regression. Mixed effects models were used to compare outcomes between groups at 3 and 6 months, and 1 year after enrollment adjusted for baseline severity and patient characteristics. Results Physical therapy was used in the first 6 weeks by 90 of 244 patients (37%) and was predicted by the absence of radiating pain and being single instead of married. Physical therapy was associated with a reduced likelihood of cross-over to surgery after 1 year (21% vs 33%, p=0.045), and greater reductions on the SF-36 physical functioning scale after 6 months (mean difference =6.0, 95% CI: 0.2, 11.7) and 1 year (mean difference =6.5, 95% CI: 0.6, 12.4). There were no differences in bodily pain or Oswestry scores across time. Conclusion Many patients with lumbar spinal stenosis pursuing conservative management receive physical therapy. Using physical therapy was associated with reduced likelihood of patients receiving surgery within 1 year. Results for other outcomes were mixed with no differences in several measures. Further research is needed to examine the effectiveness of physical therapy relative to other non-surgical management strategies for patients with lumbar spinal stenosis. PMID:24373681

[Acceptance and Commitment Therapy: Theoretical background and practice].

PubMed

Eisenbeck, Nikolett; Schlosser, Károly Kornél; Szondy, Máté; Szabó-Bartha, Anett

The Acceptance and Commitment Therapy (ACT) is one of the modern, so-called third-wave behavioural therapies. Among them the most successful is ACT, both in the number of therapists and respective scientific research. ACT's theoretical and philosophical background is described explicitly and its therapeutic interventions were developed according to this philosophy. Its psychopathological model is based on the idea that mainly the person's regulatory efforts of their own thoughts and feelings lead to psychological problems. That is, the source of human suffering and various psychological problems is the so called psychological inflexibility: control attempts of private events instead of living a life based on personal values and long-term goals. Therefore, clinical work in ACT focuses on the acceptance and defusion of the unwanted inner experiences and on the development of a meaningful life. The present article aims to provide a comprehensive description of ACT in Hungarian: its theoretical background, clinical techniques, and efficacy. At the end of the article, the state of ACT in Hungary will also be briefly discussed.

Optimal background matching camouflage.

PubMed

Michalis, Constantine; Scott-Samuel, Nicholas E; Gibson, David P; Cuthill, Innes C

2017-07-12

Background matching is the most familiar and widespread camouflage strategy: avoiding detection by having a similar colour and pattern to the background. Optimizing background matching is straightforward in a homogeneous environment, or when the habitat has very distinct sub-types and there is divergent selection leading to polymorphism. However, most backgrounds have continuous variation in colour and texture, so what is the best solution? Not all samples of the background are likely to be equally inconspicuous, and laboratory experiments on birds and humans support this view. Theory suggests that the most probable background sample (in the statistical sense), at the size of the prey, would, on average, be the most cryptic. We present an analysis, based on realistic assumptions about low-level vision, that estimates the distribution of background colours and visual textures, and predicts the best camouflage. We present data from a field experiment that tests and supports our predictions, using artificial moth-like targets under bird predation. Additionally, we present analogous data for humans, under tightly controlled viewing conditions, searching for targets on a computer screen. These data show that, in the absence of predator learning, the best single camouflage pattern for heterogeneous backgrounds is the most probable sample. © 2017 The Authors.

SU-F-J-178: A Computer Simulation Model Observer for Task-Based Image Quality Assessment in Radiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dolly, S; Mutic, S; Anastasio, M

Purpose: Traditionally, image quality in radiation therapy is assessed subjectively or by utilizing physically-based metrics. Some model observers exist for task-based medical image quality assessment, but almost exclusively for diagnostic imaging tasks. As opposed to disease diagnosis, the task for image observers in radiation therapy is to utilize the available images to design and deliver a radiation dose which maximizes patient disease control while minimizing normal tissue damage. The purpose of this study was to design and implement a new computer simulation model observer to enable task-based image quality assessment in radiation therapy. Methods: A modular computer simulation framework wasmore » developed to resemble the radiotherapy observer by simulating an end-to-end radiation therapy treatment. Given images and the ground-truth organ boundaries from a numerical phantom as inputs, the framework simulates an external beam radiation therapy treatment and quantifies patient treatment outcomes using the previously defined therapeutic operating characteristic (TOC) curve. As a preliminary demonstration, TOC curves were calculated for various CT acquisition and reconstruction parameters, with the goal of assessing and optimizing simulation CT image quality for radiation therapy. Sources of randomness and bias within the system were analyzed. Results: The relationship between CT imaging dose and patient treatment outcome was objectively quantified in terms of a singular value, the area under the TOC (AUTOC) curve. The AUTOC decreases more rapidly for low-dose imaging protocols. AUTOC variation introduced by the dose optimization algorithm was approximately 0.02%, at the 95% confidence interval. Conclusion: A model observer has been developed and implemented to assess image quality based on radiation therapy treatment efficacy. It enables objective determination of appropriate imaging parameter values (e.g. imaging dose). Framework flexibility allows for incorporation of additional modules to include any aspect of the treatment process, and therefore has great potential for both assessment and optimization within radiation therapy.« less

Left ventricular assist devices as destination therapy: a new look at survival.

PubMed

Park, Soon J; Tector, Alfred; Piccioni, William; Raines, Edward; Gelijns, Annetine; Moskowitz, Alan; Rose, Eric; Holman, William; Furukawa, Satoshi; Frazier, O Howard; Dembitsky, Walter

2005-01-01

The REMATCH trial compared the use of left ventricular assist devices with optimal medical management for patients with end-stage heart failure. When the trial met its primary end point criteria in July 2001, left ventricular assist device therapy was shown to significantly improve survival and quality of life. With extended follow-up, 2 critical questions emerge: (1) Did these benefits persist, and (2) did outcomes improve over the course of the trial, given the evolving nature of the technology? We analyzed survival in this randomized trial by using the product-limit method of Kaplan and Meier. Changes in the benefits of therapy were analyzed by examining the effect of the enrollment period. The survival rates for patients receiving left ventricular assist devices (n = 68) versus patients receiving optimal medical management (n = 61) were 52% versus 28% at 1 year and 29% versus 13% at 2 years ( P = .008, log-rank test). As of July 2003, 11 patients were alive on left ventricular assist device support out of a total 16 survivors (including 3 patients receiving optimal medical management who crossed over to left ventricular assist device therapy). There was a significant improvement in survival for left ventricular assist device-supported patients who enrolled during the second half of the trial compared with the first half ( P = .03). The Minnesota Living with Heart Failure scores improved significantly over the course of the trial. The extended follow-up confirms the initial observation that left ventricular assist device therapy renders significant survival and quality-of-life benefits compared with optimal medical management for patients with end-stage heart failure. Furthermore, we observed an improvement in the survival of patients receiving left ventricular assist devices over the course of the trial, suggesting the effect of greater clinical experience.

Impact of adherence on the outcome of antiviral therapy for chronic hepatitis C.

PubMed

Mulhall, Brian P; Younossi, Zobair

2005-01-01

Nearly 4 million people in the United States have evidence of hepatitis C infection (HCV), representing a significant cause of cirrhosis and liver cancer as well a major burden to our healthcare systems and society. Antiviral therapy can successfully eradicate HCV over the long term, potentially reducing the risk of progression and improving patients' quality of life. The currently preferred HCV treatment is a combination of pegylated interferon alfa and ribavirin, which can achieve an overall sustained viral eradication rate of 55%. The duration of this treatment is typically determined by HCV genotype and the patient's early virologic response to the antiviral regimen. Evidence has accumulated over the past few years to indicate that close adherence to the optimal antiviral regimen can enhance sustained virologic response. But optimal treatment outcomes require diligence and careful management of side effects related to combination therapy. Although reducing the dose of pegylated interferon alfa, ribavirin, or both can effectively treat side effects, suboptimal doses of this regimen, especially ribavirin, may negatively affect virologic response. An alternative strategy is to use growth factors to treat cytopenias. This strategy can obviate dose reductions while potentially improving patients' quality of life. Patient support seems especially important early after the initiation of antiviral therapy. Encouraging study findings involving the growth factors, epoetin alfa and darbepoetin alfa, suggest improved anemia and quality of life while maintaining the optimal ribavirin dose. Future work should be aimed at providing stronger evidence for the use of these "supportive products" during anti-HCV therapy. As we strive to develop better treatment options for our HCV patients, the importance of adhering to the treatment regimen continues to play a central role. Effective side effect management is crucial for the success of this treatment because adherence is negatively affected by side effects related to the antiviral regimen. By identifying and addressing the important side effects of combination therapy for HCV, adherence to treatment can be improved and optimal outcomes can be achieved.

Current challenges in optimizing systemic therapy for patients with pancreatic cancer: expert perspectives from the Australasian Gastrointestinal Trials Group (AGITG) with invited international faculty.

PubMed

Segelov, Eva; Lordick, Florian; Goldstein, David; Chantrill, Lorraine A; Croagh, Daniel; Lawrence, Ben; Arnold, Dirk; Chau, Ian; Obermannova, Radka; Price, Timothy Jay

2017-10-01

Despite recent progress, the outlook for most patients with pancreatic cancer remains poor. There is variation in how patients are managed globally due to differing interpretations of the evidence, partly because studies in this disease are challenging to undertake. This article collates the evidence upon which current best practice is based and offers an expert opinion from an international faculty on how latest developments should influence current treatment paradigms. Areas covered: Optimal chemotherapy for first and subsequent lines of therapy; optimal management of locally advanced, non-metastatic cancer including the role of neoadjuvant chemo(radio)therapy, current evidence for adjuvant chemotherapy, major advances in pancreatic cancer genomics and challenges in supportive care particularly relevant to patients with pancreatic cancer. For each section, literature was reviewed by comprehensive search techniques, including clinical trial websites and abstracts from international cancer meetings. Expert commentary: For each section, a commentary is provided. Overall the challenges identified were: difficulties in diagnosing pancreatic cancer early, challenges for performing randomised clinical trials in all stages of the disease, some progress in systemic therapy with new agents and in identifying molecular subtypes that may be clinically relevant and move towards personalized therapy, but still, pancreatic cancer remains a very poor prognosis cancer with significant palliative care needs.

Challenges with Evidence-Based Management of Stable Ischemic Heart Disease.

PubMed

Patel, Amit V; Bangalore, Sripal

2017-02-01

Stable ischemic heart disease (SIHD) is a highly prevalent condition associated with increased costs, morbidity, and mortality. Management goals of SIHD can broadly be thought of in terms of improving prognosis and/or improving symptoms. Treatment options include medical therapy as well as revascularization, either with percutaneous coronary intervention or coronary artery bypass grafting. Herein, we will review the current evidence base for treatment of SIHD as well as its challenges and discuss ongoing studies to help address some of these knowledge gaps. There has been no consistent reduction in death or myocardial infarction (MI) with revascularization vs. medical therapy in patients with SIHD in contemporary trials. Angina and quality of life have been shown to be relieved more rapidly with revascularization vs. optimal medical therapy; however, the durability of these results is uncertain. There have been challenges and limitations in several of the trials addressing the optimal treatment strategy for SIHD due to potential selection bias (due to knowledge of coronary anatomy prior to randomization), patient crossover, and advances in medical therapy and revascularization strategies since trial completion. The challenges inherent to prior trials addressing the optimal management strategy for SIHD have impacted the generalizability of results to real-world cohorts. Until the results of additional ongoing trials are available, the decision for revascularization or medical therapy should be based on patients' symptoms, weighing the risks and benefits of each approach, and patient preference.

Wireless gyroscope platform enabled by a portable media device for quantifying wobble board therapy.

PubMed

LeMoyne, Robert; Mastroianni, Timothy

2017-07-01

The wobble board enables a therapy strategy for rehabilitation of the ankle foot complex. Quantification of therapy, such as through the use of a wobble board, can facilitate a therapist's acuity for advancing and optimizing the overall therapy strategy. The portable media device, such as an iPod, can be equipped with a software application to function as a wireless gyroscope platform. Integration of the wobble board with the portable media device functioning as a wireless gyroscope enables the potential for patient to therapist interaction through connectivity to the Internet. A patient can conduct wobble board therapy for the ankle foot complex from the convenient vantage point of a homebound setting with therapy data transmitted wirelessly as email attachments. The gyroscope signal of the wobble board therapy can be consolidated into a feature set for machine learning classification. Using a multilayer perceptron neural network considerable classification accuracy has been achieved for differentiating between a hemiplegic affected ankle and unaffected ankle while using a wobble board. The combination of machine learning, wireless systems, such as a portable media device functioning as a wireless gyroscope, and a conventional therapy device, such as a wobble board, are envisioned to advance the capability to optimally impact the rehabilitation experience.

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

PubMed

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. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

State-of-the-Art Diagnosis and Treatment of Melanoma: Optimal Multidetector Computed Tomographic Practice to Identify Metastatic Disease and Review of Innovative Therapeutic Agents.

PubMed

Jones, Blake C; Lipson, Evan J; Childers, Brandon; Fishman, Elliot K; Johnson, Pamela T

The incidence of melanoma has risen dramatically over the past several decades. Oncologists rely on the ability of radiologists to identify subtle radiographic changes representing metastatic and recurrent melanoma in uncommon locations on multidetector computed tomography (MDCT) as the front-line imaging surveillance tool. To accomplish this goal, MDCT acquisition and display must be optimized and radiologist interpretation and search patterns must be tailored to identify the unique and often subtle metastatic lesions of melanoma. This article describes MDCT acquisition and display techniques that optimize the visibility of melanoma lesions, such as high-contrast display windows and multiplanar reconstructions. In addition, innovative therapies for melanoma, such as immunotherapy and small-molecule therapy, have altered clinical management and outcomes and have also changed the spectrum of therapeutic complications that can be detected on MDCT. Recent advances in melanoma therapy and potential complications that the radiologist can identify on MDCT are reviewed.

The Toronto Consensus Statements for the Management of Inflammatory Bowel Disease in Pregnancy.

PubMed

Nguyen, Geoffrey C; Seow, Cynthia H; Maxwell, Cynthia; Huang, Vivian; Leung, Yvette; Jones, Jennifer; Leontiadis, Grigorios I; Tse, Frances; Mahadevan, Uma; van der Woude, C Janneke

2016-03-01

The management of inflammatory bowel disease (IBD) poses a particular challenge during pregnancy because the health of both the mother and the fetus must be considered. A systematic literature search identified studies on the management of IBD during pregnancy. The quality of evidence and strength of recommendations were rated using the Grading of Recommendation Assessment, Development and Evaluation (GRADE) approach. Consensus was reached on 29 of the 30 recommendations considered. Preconception counseling and access to specialist care are paramount in optimizing disease management. In general, women on 5-ASA, thiopurine, or anti-tumor necrosis factor (TNF) monotherapy for maintenance should continue therapy throughout pregnancy. Discontinuation of anti-TNF therapy or switching from combination therapy to monotherapy may be considered in very select low-risk patients. Women who have a mild to moderate disease flare while on optimized 5-ASA or thiopurine therapy should be managed with systemic corticosteroid or anti-TNF therapy, and those with a corticosteroid-resistant flare should start anti-TNF therapy. Endoscopy or urgent surgery should not be delayed during pregnancy if indicated. Decisions regarding cesarean delivery should be based on obstetric considerations and not the diagnosis of IBD alone, with the exception of women with active perianal Crohn's disease. With the exception of methotrexate, the use of medications for IBD should not influence the decision to breast-feed and vice versa. Live vaccinations are not recommended within the first 6 months of life in the offspring of women who were on anti-TNF therapy during pregnancy. Optimal management of IBD before and during pregnancy is essential to achieving favorable maternal and neonatal outcomes. Copyright © 2016 AGA Institute. Published by Elsevier Inc. All rights reserved.

Optimizing the use of antithrombotic therapy for atrial fibrillation in older people: a pharmacist-led multidisciplinary intervention.

PubMed

Bajorek, Beata V; Krass, Ines; Ogle, Susan J; Duguid, Margaret J; Shenfield, Gillian M

2005-11-01

To develop, implement, and evaluate a pharmacist-led multidisciplinary intervention in a hospital setting that would optimize antithrombotic use in elderly atrial fibrillation patients. The hypothesis that there would be an increase in the proportion of patients receiving antithrombotic therapy at discharge was tested. Evidence-based algorithms were developed to define the criteria (stroke risk vs contraindications) by which an elderly patient's requirement for antithrombotic therapy was assessed. A major Sydney teaching hospital. Two hundred eighteen consecutively admitted elderly patients (mean age 85.2) were recruited over a 6-month period. A pharmacist-coordinated multidisciplinary review process was implemented to coordinate risk assessments and subsequently recommend appropriate antithrombotic therapy, as per the algorithms. The proportion of patients receiving antithrombotic therapy was assessed on admission (preintervention), at discharge (postintervention), and postdischarge (follow-up at 3 and 6 months). As a result of the intervention, 78 patients (35.8%) required changes to their existing antithrombotic therapy. Of these changes, 60 (76.9%) were "upgrades" to more-effective treatment options (e.g., from no therapy to any agent or from aspirin to warfarin). The remaining 18 (23.1%) changes were "downgrades" to less-effective, albeit safer, options. Despite a significant increase in anti thrombotic use overall (59.6% vs 81.2%, P<.001), fewer patients received warfarin postintervention, after having been assessed as inappropriate candidates (20.7% vs 17.4%, P=.39). A pharmacist-led multidisciplinary process was successfully developed and implemented within the hospital setting to increase overall antithrombotic use. Having addressed some of the known barriers and limitations to warfarin use, these algorithms may allow allied health workers, patients, and clinicians to work collaboratively to achieve optimal and, importantly, appropriate (i.e., safe and effective) antithrombotic use in at-risk elderly patients.

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

PubMed

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.

A comprehensive formulation for volumetric modulated arc therapy planning

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nguyen, Dan; Lyu, Qihui; Ruan, Dan

2016-07-15

Purpose: Volumetric modulated arc therapy (VMAT) is a widely employed radiation therapy technique, showing comparable dosimetry to static beam intensity modulated radiation therapy (IMRT) with reduced monitor units and treatment time. However, the current VMAT optimization has various greedy heuristics employed for an empirical solution, which jeopardizes plan consistency and quality. The authors introduce a novel direct aperture optimization method for VMAT to overcome these limitations. Methods: The comprehensive VMAT (comVMAT) planning was formulated as an optimization problem with an L2-norm fidelity term to penalize the difference between the optimized dose and the prescribed dose, as well as an anisotropicmore » total variation term to promote piecewise continuity in the fluence maps, preparing it for direct aperture optimization. A level set function was used to describe the aperture shapes and the difference between aperture shapes at adjacent angles was penalized to control MLC motion range. A proximal-class optimization solver was adopted to solve the large scale optimization problem, and an alternating optimization strategy was implemented to solve the fluence intensity and aperture shapes simultaneously. Single arc comVMAT plans, utilizing 180 beams with 2° angular resolution, were generated for a glioblastoma multiforme case, a lung (LNG) case, and two head and neck cases—one with three PTVs (H&N{sub 3PTV}) and one with foue PTVs (H&N{sub 4PTV})—to test the efficacy. The plans were optimized using an alternating optimization strategy. The plans were compared against the clinical VMAT (clnVMAT) plans utilizing two overlapping coplanar arcs for treatment. Results: The optimization of the comVMAT plans had converged within 600 iterations of the block minimization algorithm. comVMAT plans were able to consistently reduce the dose to all organs-at-risk (OARs) as compared to the clnVMAT plans. On average, comVMAT plans reduced the max and mean OAR dose by 6.59% and 7.45%, respectively, of the prescription dose. Reductions in max dose and mean dose were as high as 14.5 Gy in the LNG case and 15.3 Gy in the H&N{sub 3PTV} case. PTV coverages measured by D95, D98, and D99 were within 0.25% of the prescription dose. By comprehensively optimizing all beams, the comVMAT optimizer gained the freedom to allow some selected beams to deliver higher intensities, yielding a dose distribution that resembles a static beam IMRT plan with beam orientation optimization. Conclusions: The novel nongreedy VMAT approach simultaneously optimizes all beams in an arc and then directly generates deliverable apertures. The single arc VMAT approach thus fully utilizes the digital Linac’s capability in dose rate and gantry rotation speed modulation. In practice, the new single VMAT algorithm generates plans superior to existing VMAT algorithms utilizing two arcs.« less

Optimizing coherent anti-Stokes Raman scattering by genetic algorithm controlled pulse shaping

NASA Astrophysics Data System (ADS)

Yang, Wenlong; Sokolov, Alexei

2010-10-01

The hybrid coherent anti-Stokes Raman scattering (CARS) has been successful applied to fast chemical sensitive detections. As the development of femto-second pulse shaping techniques, it is of great interest to find the optimum pulse shapes for CARS. The optimum pulse shapes should minimize the non-resonant four wave mixing (NRFWM) background and maximize the CARS signal. A genetic algorithm (GA) is developed to make a heuristic searching for optimized pulse shapes, which give the best signal the background ratio. The GA is shown to be able to rediscover the hybrid CARS scheme and find optimized pulse shapes for customized applications by itself.

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

PubMed

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

2018-01-01

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

Outcomes and Experiences of an Adapted Dialectic Behaviour Therapy Skills Training Group for People with Intellectual Disabilities

ERIC Educational Resources Information Center

Crossland, Tom; Hewitt, Olivia; Walden, Sarah

2017-01-01

Background: A growing body of evidence supports the use of Dialectic Behaviour Therapy with people with an intellectual disability. Various adaptation have been used in studies exploring the efficacy of this intervention. Method: A Dialectic Behaviour Therapy DBT skills training group was attended by people with an intellectual disability and…

A Longitudinal Assessment of Early Childhood Education with Integrated Speech Therapy for Children with Significant Language Impairment in Germany

ERIC Educational Resources Information Center

Ullrich, Dieter; Ullrich, Katja; Marten, Magret

2014-01-01

Background: In Lower Saxony, Germany, pre-school children with language- and speech-deficits have the opportunity to access kindergartens with integrated language-/speech therapy prior to attending primary school, both regular or with integrated speech therapy. It is unknown whether these early childhood education treatments are helpful and…

Multiple Voices in Charles Van Riper's Desensitization Therapy

ERIC Educational Resources Information Center

Leahy, Margaret M.

2008-01-01

Background: Charles Van Riper (1905-94) author, researcher and practitioner, was one of the major contributors to the field of stuttering in the 20th century. His series of Action Therapy videotapes provide a useful model of how therapy was implemented by a master clinician. Aims: Van Riper's session with a client is analysed to reveal how voices…

Effectiveness of Semantic Therapy for Word-Finding Difficulties in Pupils with Persistent Language Impairments: A Randomized Control Trial

ERIC Educational Resources Information Center

Ebbels, Susan H.; Nicoll, Hilary; Clark, Becky; Eachus, Beth; Gallagher, Aoife L.; Horniman, Karen; Jennings, Mary; McEvoy, Kate; Nimmo, Liz; Turner, Gail

2012-01-01

Background: Word-finding difficulties (WFDs) in children have been hypothesized to be caused at least partly by poor semantic knowledge. Therefore, improving semantic knowledge should decrease word-finding errors. Previous studies of semantic therapy for WFDs are inconclusive. Aims: To investigate the effectiveness of semantic therapy for…

Employment Selections of Resident and Non-Resident Graduates of Physical Therapy Programs in Underserved Western States

ERIC Educational Resources Information Center

Swart, Kathryn D.

2011-01-01

Background and Purpose: Physical therapy (PT) is an essential component of the healthcare system in providing a comprehensive treatment plan for patients with functional limitations. The demand for physical therapy services is projected to expand in the next eight years, leading to an increased need for practicing physical therapists. The Mountain…

Witnessing Stories: Definitional Ceremonies in Narrative Therapy with Adults Who Stutter

ERIC Educational Resources Information Center

Leahy, Margaret M.; O'Dwyer, Mary; Ryan, Fiona

2012-01-01

Background: Narrative therapy (White & Epston, 1990) was developed as an approach to counselling, as a response to the power relations that influence people's lives. Its use with people who stutter has been documented. A basic tenet of narrative therapy is that the dominant problem-saturated narrative is challenged by externalizing the problem, in…

Using Computers to Enable Self-Management of Aphasia Therapy Exercises for Word Finding: The Patient and Carer Perspective

ERIC Educational Resources Information Center

Palmer, Rebecca; Enderby, Pam; Paterson, Gail

2013-01-01

Background: Speech and language therapy (SLT) for aphasia can be difficult to access in the later stages of stroke recovery, despite evidence of continued improvement with sufficient therapeutic intensity. Computerized aphasia therapy has been reported to be useful for independent language practice, providing new opportunities for continued…

Take a Paws: Fostering Student Wellness with a Therapy Dog Program at Your University Library

ERIC Educational Resources Information Center

Lannon, Amber; Harrison, Pamela

2015-01-01

Therapy dogs are trained and socialized to provide comfort to individuals who are ill or experiencing stress. The following article explores therapy dog outreach programs in academic libraries by describing a successful venture at McGill University Library. Background, planning advice, assessment results, and recommendations are presented with an…

Just-in-Time Training for High-Risk Low-Volume Therapies: An Approach to Ensure Patient Safety.

PubMed

Helman, Stephanie; Lisanti, Amy Jo; Adams, Ann; Field, Cynthia; Davis, Katherine Finn

2016-01-01

High-risk low-volume therapies are those therapies that are practiced infrequently and yet carry an increased risk to patients because of their complexity. Staff nurses are required to competently manage these therapies to treat patients' unique needs and optimize outcomes; however, maintaining competence is challenging. This article describes implementation of Just-in-Time Training, which requires validation of minimum competency of bedside nurses managing high-risk low-volume therapies through direct observation of a return-demonstration competency checklist.

High throughput RNAi assay optimization using adherent cell cytometry

PubMed Central

2011-01-01

Background siRNA technology is a promising tool for gene therapy of vascular disease. Due to the multitude of reagents and cell types, RNAi experiment optimization can be time-consuming. In this study adherent cell cytometry was used to rapidly optimize siRNA transfection in human aortic vascular smooth muscle cells (AoSMC). Methods AoSMC were seeded at a density of 3000-8000 cells/well of a 96well plate. 24 hours later AoSMC were transfected with either non-targeting unlabeled siRNA (50 nM), or non-targeting labeled siRNA, siGLO Red (5 or 50 nM) using no transfection reagent, HiPerfect or Lipofectamine RNAiMax. For counting cells, Hoechst nuclei stain or Cell Tracker green were used. For data analysis an adherent cell cytometer, Celigo® was used. Data was normalized to the transfection reagent alone group and expressed as red pixel count/cell. Results After 24 hours, none of the transfection conditions led to cell loss. Red fluorescence counts were normalized to the AoSMC count. RNAiMax was more potent compared to HiPerfect or no transfection reagent at 5 nM siGLO Red (4.12 +/-1.04 vs. 0.70 +/-0.26 vs. 0.15 +/-0.13 red pixel/cell) and 50 nM siGLO Red (6.49 +/-1.81 vs. 2.52 +/-0.67 vs. 0.34 +/-0.19). Fluorescence expression results supported gene knockdown achieved by using MARCKS targeting siRNA in AoSMCs. Conclusion This study underscores that RNAi delivery depends heavily on the choice of delivery method. Adherent cell cytometry can be used as a high throughput-screening tool for the optimization of RNAi assays. This technology can accelerate in vitro cell assays and thus save costs. PMID:21518450

Gene therapy for prostate cancer: where are we now?

PubMed

Steiner, M S; Gingrich, J R

2000-10-01

The ability to recombine specifically and alter DNA sequences followed by techniques to transfer these sequences or even whole genes into normal and diseased cells has revolutionized medical research and ushered the clinicians of today into the age of gene therapy. We provide urologists a review of relevant background information, outline current treatment strategies and clinical trials, and delineate current challenges facing the field of gene therapy for advanced prostate cancer. We comprehensively reviewed the literature, including PubMed and recent abstract proceedings from national meetings, relevant to gene therapy and advanced prostate cancer. We selected for review literature representative of the principal scientific background for current gene therapy strategies and National Institutes of Health Recombinant DNA Advisory Committee approved clinical trials. Current prostate cancer gene therapy strategies include correcting aberrant gene expression, exploiting programmed cell death pathways, targeting critical cell biological functions, introducing toxic or cell lytic suicide genes, enhancing the immune system antitumor response and combining treatment with conventional cytotoxic chemotherapy or radiation therapy. Many challenges lie ahead for gene therapy, including improving DNA transfer efficiency to cells locally and at distant sites, enhancing levels of gene expression and overcoming immune responses that limit the time that genes are expressed. Nevertheless, despite these current challenges it is almost certain that gene therapy will be part of the urological armamentarium against prostate cancer in this century.

Practitioner Review: Adolescent alcohol use disorders: assessment and treatment issues

PubMed Central

Perepletchikova, Francheska; Krystal, John H.; Kaufman, Joan

2014-01-01

Background Alcohol use disorders in adolescents are associated with significant morbidity and mortality. Over the past decade, there has been a burgeoning of research on adolescent alcohol use disorders. Methods A summary of the alcohol assessment tools is provided, and randomized studies reviewed and synthesized to provide an overview of state of the art knowledge of treatment of adolescent alcohol use disorders. Animal models of addiction are also briefly reviewed, and the value of translational research approaches, using findings from basic studies to guide the design of clinical investigations, is also highlighted. Results Comorbidity is the rule, not the exception in adolescent alcohol use disorders. Comprehensive assessment of psychiatric and other substance use disorders, trauma experiences, and suicidality is indicated in this population to optimize selection of appropriate clinical interventions. In terms of available investigated treatments for adolescents with alcohol use disorders, Multidimensional Family Therapy and group administered Cognitive Behavioral Therapies have received the most empirical support to date. There is a paucity of research on pharmacological interventions in this patient population, and no firm treatment recommendations can be made in this area. Conclusions Given the high rate of relapse after treatment, evaluation of combined psychosocial and pharmacological interventions, and the development of novel intervention strategies are indi cated. PMID:19017028

Diffuse correlation spectroscopy (DCS) study of blood flow changes during low level laser therapy (LLLT): a preliminary report

NASA Astrophysics Data System (ADS)

Soni, Sagar; Wang, Xinlong; Liu, Hanli; Tian, Fenghua

2017-02-01

Photobiomodulation with low-power, high-fluence light in the near-infrared range (600-1100nm), also known as low level laser therapy (LLLT), has been used for promoting healing of wounds, reducing pain, and so on. Understanding its physiological effect is essential for treatment optimization and evaluation. In this study, we used diffuse correlation spectroscopy (DCS) to investigate the changes of regional blood flow in skeletal muscle induced by a single session of LLLT. DCS is an emerging optical modality to probe microvascular blood flow in human tissues in vivo. We have developed a software-based autocorrelator system with the benefits such as flexibility in raw photon count data processing, portability and low cost. LLLT was administered at the human forearm with a 1064-nm, continuous-wave laser. The emitting power was 3.4 W in an area of 13.6 cm2, corresponding to 0.25W/cm2 irradiance. The emitting duration was 10 minutes. Eight healthy adults of any ethnic background, in an age range of 18-40 years old were included. The results indicate that LLLT causes reliable changes in regional blood flow. However, it remains unclear whether these changes are physiological or attributed to the heating effect of the stimulation laser.

Infrared-Transparent Gold Nanoparticles Converted by Tumors to Infrared Absorbers Cure Tumors in Mice by Photothermal Therapy

PubMed Central

Hainfeld, James F.; O'Connor, Michael J.; Lin, Ping; Qian, Luping; Slatkin, Daniel N.; Smilowitz, Henry M.

2014-01-01

Gold nanoparticles (AuNPs) absorb light and can be used to heat and ablate tumors. The “tissue window” at ∼800 nm (near infrared, NIR) is optimal for best tissue penetration of light. Previously, large, 50–150 nm, gold nanoshells and nanorods that absorb well in the NIR have been used. Small AuNPs that may penetrate tumors better unfortunately barely absorb at 800 nm. We show that small AuNPs conjugated to anti-tumor antibodies are taken up by tumor cells that catalytically aggregate them (by enzyme degradation of antibodies and pH effects), shifting their absorption into the NIR region, thus amplifying their photonic absorption. The AuNPs are NIR transparent until they accumulate in tumor cells, thus reducing background heating in blood and non-targeted cells, increasing specificity, in contrast to constructs that are always NIR-absorptive. Treatment of human squamous cell carcinoma A431 which overexpresses epidermal growth factor receptor (EGFr) in subcutaneous murine xenografts with anti-EGFr antibodies conjugated to 15 nm AuNPs and NIR resulted in complete tumor ablation in most cases with virtually no normal tissue damage. The use of targeted small AuNPs therefore provides a potent new method of selective NIR tumor therapy. PMID:24520385

Synergistic effects of Combined Therapy: nonfocused ultrasound plus Aussie current for noninvasive body contouring

PubMed Central

Canela, Vivianne Carvalho; Crivelaro, Cinthia Nicoletti; Ferla, Luciane Zacchi; Pelozo, Gisele Marques; Azevedo, Juliana; Liebano, Richard Eloin; Nogueira, Caroline; Guidi, Renata Michelini; Grecco, Clóvis; Sant’Ana, Estela

2018-01-01

Background and objectives Nowadays, there are several noninvasive technologies being used for improving of body contouring. The objectives of this pilot study were to verify the effectiveness of the Heccus® device, emphasizing the synergism between nonfocused ultrasound plus Aussie current in the improvement of body contour, and to determine if the association of this therapy with whole-body vibration exercises can have additional positive effects in the results of the treatments. Subjects and methods Twenty healthy women aged 20–40 years participated in the study. Ten patients received Combined Therapy treatment (G1) and the other 10 participants received Combined Therapy with additional vibratory platform treatment (G2). Anthropometric and standardized photography analysis, ultrasonography, cutometry and self-adminestered questionnaires of tolerance and satisfaction levels with the treatment were used. Results Compared with baseline values, reduction of fat thickness was observed by ultrasonography in the posterior thigh area in the G1 group (P<0.05) and in the buttocks (P<0.05) and the posterior thigh areas (P<0.05) in the G2. All the treated areas in both groups showed reduction in cellulite degree in the buttocks, G1 (P<0.05) and G2 (P<0.05), and in posterior thigh areas, G1 (P<0.05) and G2 (P<0.05). Optimal improvement of skin firmness (G1, P<0.0001; G2, P=0.0034) in the treated areas was observed in both groups. Conclusion We conclude that the synergistic effects of the Combined Therapy (nonfocused ultrasound plus Aussie current) might be a good option with noninvasive body contouring treatment for improving the aspect of the cellulite, skin firmness and localized fat. If used in association with the whole-body vibratory platform, the results can be better, especially in the treatment of localized fat. Further studies with larger sample size should be performed to confirm these results. PMID:29731654

Optimizing the use of oral anticoagulant therapy for atrial fibrilation in primary care: a pharmacist-led intervention.

PubMed

Virdee, Mandeep S; Stewart, Derek

2017-02-01

Background Updated evidence-based guidelines for the management of atrial fibrillation (AF) necessitate patient review, particularly with respect to oral anticoagulants, to ensure maximum health gain around stroke prophylaxis. Objective To quantify the level of anticoagulation utilisation in patients with a CHA 2 DS 2 -VASc ≥1/≥2 (male/female) according to evidence-based guidelines and to assess the impact of a pharmacist-led intervention to optimise therapy. Setting Fifteen general medical practices in Liverpool, North-West England with a practice population of 99,129. Method GRASP-AF software was employed to interrogate patient electronic medical records to identify and risk stratify AF patients (using CHA 2 DS 2 -VASc). A pharmacist then reviewed the medical records of those of patients not anticoagulated and with a CHA 2 DS 2 -VASc ≥1/≥2 (male/female). Recommendations were discussed with a general practitioner (GP) and those patients in whom the need for anticoagulation was agreed were invited for a consultation with either the pharmacist or GP and therapy optimised where appropriate. The GPs were responsible for managing those patients referred for diagnosis confirmation or further specialist opinion. Main outcome measure Proportion of patients eligible/not eligible for anticoagulation; proportions in whom anticoagulants initiated, refused, antiplatelets discontinued. Results Five hundred and twenty-three patients (31% of patients identified with AF and a CHA 2 DS 2 -VASc ≥1/≥2 (male/female)) were not receiving an anticoagulant (26 subsequently died or left the practice leaving 497). Three hundred and eighty-two (77%) pharmacist recommendations to a GP were agreed without modification. Following outcomes of diagnostic investigations and specialist referrals, 202 (41%) patients were candidates for anticoagulation, 251 (51%) were not eligible for anticoagulation, 103 (21%) were anticoagulated (56 warfarin, 47 DOAC). Conclusion A pharmacist-led intervention re-aligned oral anticoagulant therapy to the latest evidence based guidelines for stroke prophylaxis, whilst simultaneously correcting the over-utilisation of antiplatelet therapy.

The important role of von Willebrand factor in platelet-derived FVIII gene therapy for murine hemophilia A in the presence of inhibitory antibodies.

PubMed

Shi, Q; Schroeder, J A; Kuether, E L; Montgomery, R R

2015-07-01

Our previous studies have demonstrated that targeting FVIII expression to platelets results in FVIII storage together with von Willebrand factor (VWF) in platelet α-granules and that platelet-derived FVIII (2bF8) corrects the murine hemophilia A phenotype even in the presence of high-titer anti-FVIII inhibitory antibodies (inhibitors). To explore how VWF has an impact on platelet gene therapy for hemophilia A with inhibitors. 2bF8 transgenic mice in the FVIII(-/-) background (2bF8(tg+/-) F8(-/-) ) with varying VWF phenotypes were used in this study. Animals were analyzed by VWF ELISA, FVIII activity assay, Bethesda assay and tail clip survival test. Only 18% of 2bF8(tg+/-) F8(-/-) VWF(-/-) animals, in which VWF was deficient, survived the tail clip challenge with inhibitor titers of 3-8000 BU mL(-1) . In contrast, 82% of 2bF8(tg+/-) F8(-/-) VWF(+/+) mice, which had normal VWF levels, survived tail clipping with inhibitor titers of 10-50,000 BU mL(-1) . All 2bF8(tg+/-) F8(-/-) VWF(-/-) mice without inhibitors survived tail clipping and no VWF(-/-) F8(-/-) mice survived this challenge. Because VWF is synthesized by endothelial cells and megakaryocytes and is distributed in both plasma and platelets in peripheral blood, we further investigated the effect of each compartment of VWF on platelet-FVIII gene therapy for hemophilia A with inhibitors. In the presence of inhibitors, 42% of animals survived tail clipping in the group with plasma-VWF and 50% survived in the platelet-VWF group. VWF is essential for platelet gene therapy for hemophilia A with inhibitors. Both platelet-VWF and plasma-VWF are required for optimal platelet-derived FVIII gene therapy for hemophilia A in the presence of inhibitors. © 2015 International Society on Thrombosis and Haemostasis.

Descriptive analysis of spinal neuroaxial injections, surgical interventions and physical therapy utilization for degenerative lumbar spondylolisthesis within Medicare beneficiaries from 2000–2011

PubMed Central

Sclafani, Joseph A.; Constantin, Alexandra; Ho, Pei-Shu; Akuthota, Venu; Chan, Leighton

2016-01-01

Study Design Retrospective, observational study. Objective To determine the utilization of various treatment modalities in the management of degenerative spondylolisthesis within Medicare beneficiaries. Summary of Background Data Degenerative lumbar spondylolisthesis is a condition often identified in symptomatic low back pain. A variety of treatment algorithms including physical therapy and interventional techniques can be used to manage clinically significant degenerative spondylolisthesis. Methods This study utilized the 5% national sample of Medicare carrier claims from 2000 through 2011. A cohort of beneficiaries with a new ICD-9 diagnosis code for degenerative lumbar spondylolisthesis was identified. Current procedural terminology codes were used to identify the number of procedures performed each year by specialty on this cohort. Results A total of 95,647 individuals were included in the analysis. Average age at the time of initial diagnosis was 72.8 ± 9.8 years. Within this study cohort, spondylolisthesis was more prevalent in females (69%) than males and in Caucasians (88%) compared to other racial demographics. Over 40% of beneficiaries underwent at least one injection, approximately one third (37%) participated in physical therapy, one in five (22%) underwent spinal surgery, and one third (36%) did not utilize any of these interventions. Greater than half of all procedures (124,280/216,088) occurred within 2 years of diagnosis. The ratio of focal interventions (transforaminal and facet interventions) to less selective (interlaminar) procedures was greater for the specialty of Physical Medicine and Rehabilitation compared to the specialties of Anesthesiology, Interventional Radiology, Neurosurgery, and Orthopedic Surgery. The majority of physical therapy was dedicated to passive treatment modalities and range of motion exercises rather than active strengthening modalities within this cohort. Conclusion Interventional techniques and physical therapy are frequently used treatment modalities for symptomatic degenerative spondylolisthesis. Understanding utilization of these techniques is important to determine relative clinical efficacies and to optimize future health care expenditures. PMID:28207664

Plastic Surgery Challenges in War Wounded II: Regenerative Medicine

PubMed Central

Valerio, Ian L.; Sabino, Jennifer M.; Dearth, Christopher L.

2016-01-01

Background: A large volume of service members have sustained complex injuries during Operations Iraqi Freedom (OIF) and Enduring Freedom (OEF). These injuries are complicated by contamination with particulate and foreign materials, have high rates of bacterial and/or fungal infections, are often composite-type defects with massive soft tissue wounds, and usually have multisystem involvement. While traditional treatment modalities remain a mainstay for optimal wound care, traditional reconstruction approaches alone may be inadequate to fully address the scope and magnitude of such massive complex wounds. As a result of these difficult clinical problems, the use of regenerative medicine therapies, such as autologous adipose tissue grafting, stem cell therapies, nerve allografts, and dermal regenerate templates/extracellular matrix scaffolds, is increased as adjuncts to traditional reconstructive measures. Basic and Clinical Science Advances: The beneficial applications of regenerative medicine therapies have been well characterized in both in vitro studies and in vivo animal studies. The use of these regenerative medicine techniques in the treatment of combat casualty injuries has been increasing throughout the recent war conflicts. Clinical Care Relevance: Military medicine has shown positive results when utilizing certain regenerative medicine modalities in treating complex war wounds. As a result, multi-institution clinical trials are underway to further evaluate these observations and reconstruction measures. Conclusion: Successful combat casualty wound care often requires a combination of traditional aspects of the reconstructive ladder/elevator with adoption of various regenerative medicine therapies. Due to the recent OIF/OEF conflicts, a high volume of combat casualties have benefited from adoption of regenerative medicine therapies and increased access to innovative clinical trials. Furthermore, many of these patients have had long-term follow-up to report on clinical outcomes that substantiate current treatment paradigms and concepts within regenerative medicine, reconstructive, and rehabilitation care. These results are applicable to not only combat casualty care but also to nonmilitary patients. PMID:27679752

Predicting the safety and efficacy of buffer therapy to raise tumour pHe: an integrative modelling study

PubMed Central

Martin, N K; Robey, I F; Gaffney, E A; Gillies, R J; Gatenby, R A; Maini, P K

2012-01-01

Background: Clinical positron emission tomography imaging has demonstrated the vast majority of human cancers exhibit significantly increased glucose metabolism when compared with adjacent normal tissue, resulting in an acidic tumour microenvironment. Recent studies demonstrated reducing this acidity through systemic buffers significantly inhibits development and growth of metastases in mouse xenografts. Methods: We apply and extend a previously developed mathematical model of blood and tumour buffering to examine the impact of oral administration of bicarbonate buffer in mice, and the potential impact in humans. We recapitulate the experimentally observed tumour pHe effect of buffer therapy, testing a model prediction in vivo in mice. We parameterise the model to humans to determine the translational safety and efficacy, and predict patient subgroups who could have enhanced treatment response, and the most promising combination or alternative buffer therapies. Results: The model predicts a previously unseen potentially dangerous elevation in blood pHe resulting from bicarbonate therapy in mice, which is confirmed by our in vivo experiments. Simulations predict limited efficacy of bicarbonate, especially in humans with more aggressive cancers. We predict buffer therapy would be most effectual: in elderly patients or individuals with renal impairments; in combination with proton production inhibitors (such as dichloroacetate), renal glomular filtration rate inhibitors (such as non-steroidal anti-inflammatory drugs and angiotensin-converting enzyme inhibitors), or with an alternative buffer reagent possessing an optimal pK of 7.1–7.2. Conclusion: Our mathematical model confirms bicarbonate acts as an effective agent to raise tumour pHe, but potentially induces metabolic alkalosis at the high doses necessary for tumour pHe normalisation. We predict use in elderly patients or in combination with proton production inhibitors or buffers with a pK of 7.1–7.2 is most promising. PMID:22382688

Accurate Monte Carlo simulations for nozzle design, commissioning and quality assurance for a proton radiation therapy facility.

PubMed

Paganetti, H; Jiang, H; Lee, S Y; Kooy, H M

2004-07-01

Monte Carlo dosimetry calculations are essential methods in radiation therapy. To take full advantage of this tool, the beam delivery system has to be simulated in detail and the initial beam parameters have to be known accurately. The modeling of the beam delivery system itself opens various areas where Monte Carlo calculations prove extremely helpful, such as for design and commissioning of a therapy facility as well as for quality assurance verification. The gantry treatment nozzles at the Northeast Proton Therapy Center (NPTC) at Massachusetts General Hospital (MGH) were modeled in detail using the GEANT4.5.2 Monte Carlo code. For this purpose, various novel solutions for simulating irregular shaped objects in the beam path, like contoured scatterers, patient apertures or patient compensators, were found. The four-dimensional, in time and space, simulation of moving parts, such as the modulator wheel, was implemented. Further, the appropriate physics models and cross sections for proton therapy applications were defined. We present comparisons between measured data and simulations. These show that by modeling the treatment nozzle with millimeter accuracy, it is possible to reproduce measured dose distributions with an accuracy in range and modulation width, in the case of a spread-out Bragg peak (SOBP), of better than 1 mm. The excellent agreement demonstrates that the simulations can even be used to generate beam data for commissioning treatment planning systems. The Monte Carlo nozzle model was used to study mechanical optimization in terms of scattered radiation and secondary radiation in the design of the nozzles. We present simulations on the neutron background. Further, the Monte Carlo calculations supported commissioning efforts in understanding the sensitivity of beam characteristics and how these influence the dose delivered. We present the sensitivity of dose distributions in water with respect to various beam parameters and geometrical misalignments. This allows the definition of tolerances for quality assurance and the design of quality assurance procedures.

An assessment of antibiotic therapy of urinary tract infection in elderly, hospitalised patients.

PubMed

McCaig, D J; Stewart, D; Harvey, Y; Downie, G; Scott, C J

1995-11-01

The aim of the study was to compare the antibiotic treatment actually received by elderly, hospitalised patients with urinary tract infection (UTI) with 'optimal' therapy (as gauged by compliance with antibiotic policy, infecting organism, sensitivity data, patient renal function and cost). UTI was more common in females and in catheterised patients and E.Coli was the commonest pathogen. Trimethoprim and co-amoxiclav were the drugs used most frequently for either empirical or sensitivity data-based treatment. In 96% of infections a drug with appropriate action was administered. Often, however, treatment could have been optimised by substituting a cheaper suitable antibiotic, by standardising duration of therapy and ensuring that doses were adjusted for renal impairment. Savings from the use of 'optimal' therapy were estimated at 17%. There is clearly considerable scope for positive input from the clinical pharmacist in this area.

An Expert Opinion on Advanced Insulin Pump Use in Youth with Type 1 Diabetes.

PubMed

Bode, Bruce W; Kaufman, Francine R; Vint, Nan

2017-03-01

Among children and adolescents with type 1 diabetes mellitus, the use of insulin pump therapy has increased since its introduction in the early 1980s. Optimal management of type 1 diabetes mellitus depends on sufficient understanding by patients, their families, and healthcare providers on how to use pump technology. The goal for the use of insulin pump therapy should be to advance proficiency over time from the basics taught at the initiation of pump therapy to utilizing advanced settings to obtain optimal glycemic control. However, this goal is often not met, and appropriate understanding of the full features of pump technology can be lacking. The objective of this review is to provide an expert perspective on the advanced features and use of insulin pump therapy, including practical guidelines for the successful use of insulin pump technology, and other considerations specific to patients and healthcare providers.

Pulmonary surfactant for neonatal respiratory disorders.

PubMed

Merrill, Jeffrey D; Ballard, Roberta A

2003-04-01

Surfactant therapy has revolutionized neonatal care and is used routinely for preterm infants with respiratory distress syndrome. Recent investigation has further elucidated the function of surfactant-associated proteins and their contribution toward surfactant and lung immune defense functions. As the field of neonatology moves away from intubation and mechanical ventilation of preterm infants at birth toward more aggressive use of nasal continuous positive airway pressure, the optimal timing of exogenous surfactant therapy remains unclear. Evidence suggests that preterm neonates with bronchopulmonary dysplasia and prolonged mechanical ventilation also experience surfactant dysfunction; however, exogenous surfactant therapy beyond the first week of life has not been well studied. Surfactant replacement therapy has been studied for use in other respiratory disorders, including meconium aspiration syndrome and pneumonia. Commercial surfactant preparations currently available are not optimal, given the variability of surfactant protein content and their susceptibility to inhibition. Further progress in the treatment of neonatal respiratory disorders may include the development of "designer" surfactant preparations.

Management of Gastroesophageal Reflux Disease.

PubMed

Gyawali, C Prakash; Fass, Ronnie

2018-01-01

Management of gastroesophageal reflux disease (GERD) commonly starts with an empiric trial of proton pump inhibitor (PPI) therapy and complementary lifestyle measures, for patients without alarm symptoms. Optimization of therapy (improving compliance and timing of PPI doses), or increasing PPI dosage to twice daily in select circumstances, can reduce persistent symptoms. Patients with continued symptoms can be evaluated with endoscopy and tests of esophageal physiology, to better determine their disease phenotype and optimize treatment. Laparoscopic fundoplication, magnetic sphincter augmentation, and endoscopic therapies can benefit patients with well-characterized GERD. Patients with functional diseases that overlap with or mimic GERD can also be treated with neuromodulators (primarily antidepressants), or psychological interventions (psychotherapy, hypnotherapy, cognitive and behavioral therapy). Future approaches to treatment of GERD include potassium-competitive acid blockers, reflux-reducing agents, bile acid binders, injection of inert substances into the esophagogastric junction, and electrical stimulation of the lower esophageal sphincter. Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.

Use of the Occupational Therapy Task-Oriented Approach to optimize the motor performance of a client with cognitive limitations.

PubMed

Preissner, Katharine

2010-01-01

This case report describes the use of the Occupational Therapy Task-Oriented Approach with a client with occupational performance limitations after a cerebral vascular accident. The Occupational Therapy Task-Oriented Approach is often suggested as a preferred neurorehabilitation intervention to improve occupational performance by optimizing motor behavior. One common critique of this approach, however, is that it may seem inappropriate or have limited application for clients with cognitive deficits. This case report demonstrates how an occupational therapist working in an inpatient rehabilitation setting used the occupational therapy task-oriented evaluation framework and treatment principles described by Mathiowetz (2004) with a person with significant cognitive limitations. This approach was effective in assisting the client in meeting her long-term goals, maximizing her participation in meaningful occupations, and successfully transitioning to home with her daughter.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Taleei, R; Qin, N; Jiang, S

2016-06-15

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

A Methodology for Optimizing the Training and Utilization of Physical Therapy Personnel.

ERIC Educational Resources Information Center

Dumas, Neil S.; Muthard, John E.

A method for analyzing the work in a department of physical therapy was devised and applied in a teaching hospital. Physical therapists, trained as observer-investigators, helped refine the coding system and were able to reliably record job behavior in the physical therapy department. The nature of the therapist's and aide's job was described and…

When to Initiate Combined Antiretroviral Therapy to Reduce Mortality and AIDS-Defining Illness in HIV-Infected Persons in Developed Countries

PubMed Central

2012-01-01

Background Most clinical guidelines recommend that AIDS-free, HIV-infected persons with CD4 cell counts below 0.350 × 109 cells/L initiate combined antiretroviral therapy (cART), but the optimal CD4 cell count at which cART should be initiated remains a matter of debate. Objective To identify the optimal CD4 cell count at which cART should be initiated. Design Prospective observational data from the HIV-CAUSAL Collaboration and dynamic marginal structural models were used to compare cART initiation strategies for CD4 thresholds between 0.200 and 0.500 × 109 cells/L. Setting HIV clinics in Europe and the Veterans Health Administration system in the United States. Patients 20 971 HIV-infected, therapy-naive persons with baseline CD4 cell counts at or above 0.500 × 109 cells/L and no previous AIDS-defining illnesses, of whom 8392 had a CD4 cell count that decreased into the range of 0.200 to 0.499 × 109 cells/L and were included in the analysis. Measurements Hazard ratios and survival proportions for all-cause mortality and a combined end point of AIDS-defining illness or death. Results Compared with initiating cART at the CD4 cell count threshold of 0.500 × 109 cells/L, the mortality hazard ratio was 1.01 (95% CI, 0.84 to 1.22) for the 0.350 threshold and 1.20 (CI, 0.97 to 1.48) for the 0.200 threshold. The corresponding hazard ratios were 1.38 (CI, 1.23 to 1.56) and 1.90 (CI, 1.67 to 2.15), respectively, for the combined end point of AIDS-defining illness or death. Limitations CD4 cell count at cART initiation was not randomized. Residual confounding may exist. Conclusion Initiation of cART at a threshold CD4 count of 0.500 × 109 cells/L increases AIDS-free survival. However, mortality did not vary substantially with the use of CD4 thresholds between 0.300 and 0.500 ×109 cells/L. Primary Funding Source National Institutes of Health. PMID:21502648

Prevention and management of hepatitis B virus reactivation in patients with hematological malignancies treated with anticancer therapy

PubMed Central

Law, Man Fai; Ho, Rita; Cheung, Carmen K M; Tam, Lydia H P; Ma, Karen; So, Kent C Y; Ip, Bonaventure; So, Jacqueline; Lai, Jennifer; Ng, Joyce; Tam, Tommy H C

2016-01-01

Hepatitis due to hepatitis B virus (HBV) reactivation can be severe and potentially fatal, but is preventable. HBV reactivation is most commonly reported in patients receiving cancer chemotherapy, especially rituximab-containing therapy for hematological malignancies and those receiving stem cell transplantation. All patients with hematological malignancies receiving anticancer therapy should be screened for active or resolved HBV infection by blood tests for hepatitis B surface antigen (HBsAg) and antibody to hepatitis B core antigen (anti-HBc). Patients found to be positive for HBsAg should be given prophylactic antiviral therapy to prevent HBV reactivation. For patients with resolved HBV infection, no standard strategy has yet been established to prevent HBV reactivation. There are usually two options. One is pre-emptive therapy guided by serial HBV DNA monitoring, whereby antiviral therapy is given as soon as HBV DNA becomes detectable. However, there is little evidence regarding the optimal interval and period of monitoring. An alternative approach is prophylactic antiviral therapy, especially for patients receiving high-risk therapy such as rituximab, newer generation of anti-CD20 monoclonal antibody, obinutuzumab or hematopoietic stem cell transplantation. This strategy may effectively prevent HBV reactivation and avoid the inconvenience of repeated HBV DNA monitoring. Entecavir or tenofovir are preferred over lamivudine as prophylactic therapy. Although there is no well-defined guideline on the optimal duration of prophylactic therapy, there is growing evidence to recommend continuing prophylactic antiviral therapy for at least 12 mo after cessation of chemotherapy, and even longer for those who receive rituximab or who had high serum HBV DNA levels before the start of immunosuppressive therapy. Many novel agents have recently become available for the treatment of hematological malignancies, and these agents may be associated with HBV reactivation. Although there is currently limited evidence to guide the optimal preventive measures, we recommend antiviral prophylaxis in HBsAg-positive patients receiving novel treatments, especially the Bruton tyrosine kinase inhibitors and the phosphatidylinositol 3-kinase inhibitors, which are B-cell receptor signaling modulators and reduce proliferation of malignant B-cells. Further studies are needed to clarify the risk of HBV reactivation with these agents and the best prophylactic strategy in the era of targeted therapy for hematological malignancies. PMID:27605883

Cross-Cultural Approaches to Addict Families.

ERIC Educational Resources Information Center

Coleman, Sandra B.

1979-01-01

From a national survey of family therapy and drug abuse treatment, diverse methods of treating families from varying ethnic/minority backgrounds have been derived in an effort to integrate both family and environmental systems theory--an "ecological" family therapy approach. (Author)

Antibiotic Desensitization Therapy in Secondary Syphilis and Listeria Infection: Case Reports and Review of Desensitization Therapy

PubMed Central

Magpantay, Gil; Madar, Cristian S; Hsue, Gunther; Belnap, Conrad

2011-01-01

Two adult cases, one of secondary syphilis and one of Listeria monocytogenes bacteremia, in which antibiotic desensitization therapy was utilized to assist treatment of active infection in the face of severe penicillin allergy. Clinical considerations are discussed that led to the decision to employ a formal desensitization procedure. Antibiotic desensitization protocols can facilitate optimal and safe antibiotic therapy in the appropriate clinical setting. PMID:22187514

A Systems Approach to Designing Effective Clinical Trials Using Simulations

PubMed Central

Fusaro, Vincent A.; Patil, Prasad; Chi, Chih-Lin; Contant, Charles F.; Tonellato, Peter J.

2013-01-01

Background Pharmacogenetics in warfarin clinical trials have failed to show a significant benefit compared to standard clinical therapy. This study demonstrates a computational framework to systematically evaluate pre-clinical trial design of target population, pharmacogenetic algorithms, and dosing protocols to optimize primary outcomes. Methods and Results We programmatically created an end-to-end framework that systematically evaluates warfarin clinical trial designs. The framework includes options to create a patient population, multiple dosing strategies including genetic-based and non-genetic clinical-based, multiple dose adjustment protocols, pharmacokinetic/pharmacodynamics (PK/PD) modeling and international normalization ratio (INR) prediction, as well as various types of outcome measures. We validated the framework by conducting 1,000 simulations of the CoumaGen clinical trial primary endpoints. The simulation predicted a mean time in therapeutic range (TTR) of 70.6% and 72.2% (P = 0.47) in the standard and pharmacogenetic arms, respectively. Then, we evaluated another dosing protocol under the same original conditions and found a significant difference in TTR between the pharmacogenetic and standard arm (78.8% vs. 73.8%; P = 0.0065), respectively. Conclusions We demonstrate that this simulation framework is useful in the pre-clinical assessment phase to study and evaluate design options and provide evidence to optimize the clinical trial for patient efficacy and reduced risk. PMID:23261867

Design of clinical trials involving multiple hypothesis tests with a common control.

PubMed

Schou, I Manjula; Marschner, Ian C

2017-07-01

Randomized clinical trials comparing several treatments to a common control are often reported in the medical literature. For example, multiple experimental treatments may be compared with placebo, or in combination therapy trials, a combination therapy may be compared with each of its constituent monotherapies. Such trials are typically designed using a balanced approach in which equal numbers of individuals are randomized to each arm, however, this can result in an inefficient use of resources. We provide a unified framework and new theoretical results for optimal design of such single-control multiple-comparator studies. We consider variance optimal designs based on D-, A-, and E-optimality criteria, using a general model that allows for heteroscedasticity and a range of effect measures that include both continuous and binary outcomes. We demonstrate the sensitivity of these designs to the type of optimality criterion by showing that the optimal allocation ratios are systematically ordered according to the optimality criterion. Given this sensitivity to the optimality criterion, we argue that power optimality is a more suitable approach when designing clinical trials where testing is the objective. Weighted variance optimal designs are also discussed, which, like power optimal designs, allow the treatment difference to play a major role in determining allocation ratios. We illustrate our methods using two real clinical trial examples taken from the medical literature. Some recommendations on the use of optimal designs in single-control multiple-comparator trials are also provided. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Selective robust optimization: A new intensity-modulated proton therapy optimization strategy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Yupeng; Niemela, Perttu; Siljamaki, Sami

2015-08-15

Purpose: To develop a new robust optimization strategy for intensity-modulated proton therapy as an important step in translating robust proton treatment planning from research to clinical applications. Methods: In selective robust optimization, a worst-case-based robust optimization algorithm is extended, and terms of the objective function are selectively computed from either the worst-case dose or the nominal dose. Two lung cancer cases and one head and neck cancer case were used to demonstrate the practical significance of the proposed robust planning strategy. The lung cancer cases had minimal tumor motion less than 5 mm, and, for the demonstration of the methodology,more » are assumed to be static. Results: Selective robust optimization achieved robust clinical target volume (CTV) coverage and at the same time increased nominal planning target volume coverage to 95.8%, compared to the 84.6% coverage achieved with CTV-based robust optimization in one of the lung cases. In the other lung case, the maximum dose in selective robust optimization was lowered from a dose of 131.3% in the CTV-based robust optimization to 113.6%. Selective robust optimization provided robust CTV coverage in the head and neck case, and at the same time improved controls over isodose distribution so that clinical requirements may be readily met. Conclusions: Selective robust optimization may provide the flexibility and capability necessary for meeting various clinical requirements in addition to achieving the required plan robustness in practical proton treatment planning settings.« less

Pitfalls of tungsten multileaf collimator in proton beam therapy.

PubMed

Moskvin, Vadim; Cheng, Chee-Wai; Das, Indra J

2011-12-01

Particle beam therapy is associated with significant startup and operational cost. Multileaf collimator (MLC) provides an attractive option to improve the efficiency and reduce the treatment cost. A direct transfer of the MLC technology from external beam radiation therapy is intuitively straightforward to proton therapy. However, activation, neutron production, and the associated secondary cancer risk in proton beam should be an important consideration which is evaluated. Monte Carlo simulation with FLUKA particle transport code was applied in this study for a number of treatment models. The authors have performed a detailed study of the neutron generation, ambient dose equivalent [H∗(10)], and activation of a typical tungsten MLC and compared with those obtained from a brass aperture used in a typical proton therapy system. Brass aperture and tungsten MLC were modeled by absorber blocks in this study, representing worst-case scenario of a fully closed collimator. With a tungsten MLC, the secondary neutron dose to the patient is at least 1.5 times higher than that from a brass aperture. The H∗(10) from a tungsten MLC at 10 cm downstream is about 22.3 mSv/Gy delivered to water phantom by noncollimated 200 MeV beam of 20 cm diameter compared to 14 mSv/Gy for the brass aperture. For a 30-fraction treatment course, the activity per unit volume in brass aperture reaches 5.3 × 10⁴ Bq cm(-3) at the end of the last treatment. The activity in brass decreases by a factor of 380 after 24 h, additional 6.2 times after 40 days of cooling, and is reduced to background level after 1 yr. Initial activity in tungsten after 30 days of treating 30 patients per day is about 3.4 times higher than in brass that decreases only by a factor of 2 after 40 days and accumulates to 1.2 × 10⁶ Bq cm(-3) after a full year of operation. The daily utilization of the MLC leads to buildup of activity with time. The overall activity continues to increase due to (179)Ta with a half-life of 1.82 yr and thus require prolonged storage for activity cooling. The H∗(10) near the patient side of the tungsten block is about 100 μSv/h and is 27 times higher at the upstream side of the block. This would lead to an accumulated dose for therapists in a year that may exceed occupational maximum permissible dose (50 mSv/yr). The value of H∗(10) at the upstream surface of the tungsten block is about 220 times higher than that of the brass. MLC is an efficient way for beam shaping and overall cost reduction device in proton therapy. However, based on this study, tungsten seems to be not an optimal material for MLC in proton beam therapy. Usage of tungsten MLC in clinic may create unnecessary risks associated with the secondary neutrons and induced radioactivity for patients and staff depending on the patient load. A careful selection of material for manufacturing of an optimal MLC for proton therapy is thus desired.

Antiretroviral therapy provided to HIV-infected Malawian women in a randomized trial diminishes the posiitive effect of lipid-based nutrient supplements on breast milk B-vitamins

USDA-ARS?s Scientific Manuscript database

Background: There is little information on B-vitamin concentrations in human milk or how they are affected by maternal B-vitamin deficiencies, antiretroviral (ARV) therapy or maternal supplementation. Objective: To evaluate effects of ARV therapy and/or lipid-based nutrient supplements (LNS) on B-v...

Do Video Reviews of Therapy Sessions Help People with Mild Intellectual Disabilities Describe Their Perceptions of Cognitive Behaviour Therapy?

ERIC Educational Resources Information Center

Burford, B.; Jahoda, A.

2012-01-01

Background: This study examined the potential of a retrospective video reviewing process [Burford Reviewing Process (BRP)] for enabling people with intellectual disabilities to describe their experiences of cognitive behaviour therapy (CBT). It is the first time that the BRP, described in this paper, has been used with people with intellectual…

Evidence to Practice Commentary: Is More Therapy Better?

ERIC Educational Resources Information Center

Novak, Iona

2012-01-01

Parents seek sustained intense "hands-on" therapy for their children based on a belief that "more is better." Since the core objective of evidence-based practice (EBP) is to do the right things, for the right child, at the right time, and to optimize intervention outcomes, it is vital to know what the literature says about how much therapy to…

[Intensive therapy for patients with Guillian-Barré syndrome].

PubMed

Buus, Lone; Tønnesen, Else K

2014-10-13

Guillain-Barré syndrome is the leading cause of acute flaccid paralysis in the industrialized world. Approximately 25% of the patients suffering from Guillain-Barré syndrome develop respiratory failure requiring mechanical ventilation and intensive therapy. We seek answers to when it is optimal to start respiratory supportive therapy and review various complications associated with Guillain-Barré syndrome.

Optimizing Quality of Life in Patients with Hormone Receptor-Positive Metastatic Breast Cancer: Treatment Options and Considerations.

PubMed

Chalasani, Pavani

2017-01-01

The treatment landscape for hormone receptor-positive metastatic breast cancer continues to evolve as the molecular mechanisms of this heterogeneous disease are better understood and targeted treatment strategies are developed. Patients are now living for extended periods of time with this disease as they progress through sequential lines of treatment. With a rapidly expanding therapeutic armamentarium, the prevalence of metastatic breast cancer patients with prolonged survival is expected to increase, as is the duration of survival. Practice guidelines recommend endocrine therapy alone as first-line therapy for the majority of patients with metastatic hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer. The approval of new agents and expanded combination options has extended their use beyond first line, but endocrine therapy is not used as widely in clinical practice as recommended. As all treatments are palliative, even as survival is prolonged, optimizing and maintaining patient quality of life is crucial. This article surveys data relevant to the use of endocrine therapy in the setting of hormone receptor-positive metastatic breast cancer, including key clinical evidence regarding approved therapies and the impact of these therapies on patient quality of life. © 2017 S. Karger AG, Basel.

Treatment Perspectives in Crohn's Disease.

PubMed

Vetter, Marcel; Neurath, Markus F

2018-06-05

Crohn's disease (CD) is a chronic immune-mediated disorder of the gastrointestinal tract. The pathophysiological understanding of this disease is limited and no curative therapy is available so far. Therefore, most patients require long-lasting or even life-long immunosuppressive therapies for the suppression of symptoms to improve quality of life and reduction of long-term risks. However, in a relevant subgroup of patients, these therapeutic goals cannot be sufficiently attained. Clinically established therapies in active CD comprise corticosteroids and immunosuppressants such as azathioprine. After the introduction of anti-TNFα (Tumor necrosis factor alpha) antibodies, other biologicals (e.g., vedolizumab and ustekinumab) have also been approved. New drugs in the pipeline like filgotinib, upadacitinib, risankizumab or rifaximin could improve the therapy of CD in the near future. Thus, an individualized therapy management, based on optimal selection of therapeutic agents will become more important. Additionally, the local application of mesenchymal stem cells might be helpful in the management of fistulas. Key Messages: The targeted biological therapeutic agents (anti-TNFα antibodies, vedolizumab, ustekinumab) are well established for therapy in CD. There are several new substances in the pipeline with promising results in phase II trials (filgotinib, rifaximin, risankizumab, upadacitinib). The upcoming extension of the therapeutic arsenal will require methods for an optimized selection of substances, thus enabling a more individualized therapy. © 2018 S. Karger AG, Basel.

Optimal Clinical Doses of Faropenem, Linezolid, and Moxifloxacin in Children With Disseminated Tuberculosis: Goldilocks

PubMed Central

Srivastava, Shashikant; Deshpande, Devyani; Pasipanodya, Jotam; Nuermberger, Eric; Swaminathan, Soumya; Gumbo, Tawanda

2016-01-01

Background. When treated with the same antibiotic dose, children achieve different 0- to 24-hour area under the concentration-time curves (AUC0–24) because of maturation and between-child physiological variability on drug clearance. Children are also infected by Mycobacterium tuberculosis isolates with different antibiotic minimum inhibitory concentrations (MICs). Thus, each child will achieve different AUC0–24/MIC ratios when treated with the same dose. Methods. We used 10 000-subject Monte Carlo experiments to identify the oral doses of linezolid, moxifloxacin, and faropenem that would achieve optimal target exposures associated with optimal efficacy in children with disseminated tuberculosis. The linezolid and moxifloxacin exposure targets were AUC0–24/MIC ratios of 62 and 122, and a faropenem percentage of time above MIC >60%, in combination therapy. A linezolid AUC0–24 of 93.4 mg × hour/L was target for toxicity. Population pharmacokinetic parameters of each drug and between-child variability, as well as MIC distribution, were used, and the cumulative fraction of response (CFR) was calculated. We also considered drug penetration indices into meninges, bone, and peritoneum. Results. The linezolid dose of 15 mg/kg in full-term neonates and infants aged up to 3 months and 10 mg/kg in toddlers, administered once daily, achieved CFR ≥ 90%, with <10% achieving linezolid AUC0–24 associated with toxicity. The moxifloxacin dose of 25 mg/kg/day achieved a CFR > 90% in infants, but the optimal dose was 20 mg/kg/day in older children. The faropenem medoxomil optimal dosage was 30 mg/kg 3–4 times daily. Conclusions. The regimen and doses of linezolid, moxifloxacin, and faropenem identified are proposed to be adequate for all disseminated tuberculosis syndromes, whether drug-resistant or -susceptible. PMID:27742641

Epicardial left ventricular lead placement for cardiac resynchronization therapy: optimal pace site selection with pressure-volume loops.

PubMed

Dekker, A L A J; Phelps, B; Dijkman, B; van der Nagel, T; van der Veen, F H; Geskes, G G; Maessen, J G

2004-06-01

Patients in heart failure with left bundle branch block benefit from cardiac resynchronization therapy. Usually the left ventricular pacing lead is placed by coronary sinus catheterization; however, this procedure is not always successful, and patients may be referred for surgical epicardial lead placement. The objective of this study was to develop a method to guide epicardial lead placement in cardiac resynchronization therapy. Eleven patients in heart failure who were eligible for cardiac resynchronization therapy were referred for surgery because of failed coronary sinus left ventricular lead implantation. Minithoracotomy or thoracoscopy was performed, and a temporary epicardial electrode was used for biventricular pacing at various sites on the left ventricle. Pressure-volume loops with the conductance catheter were used to select the best site for each individual patient. Relative to the baseline situation, biventricular pacing with an optimal left ventricular lead position significantly increased stroke volume (+39%, P =.01), maximal left ventricular pressure derivative (+20%, P =.02), ejection fraction (+30%, P =.007), and stroke work (+66%, P =.006) and reduced end-systolic volume (-6%, P =.04). In contrast, biventricular pacing at a suboptimal site did not significantly change left ventricular function and even worsened it in some cases. To optimize cardiac resynchronization therapy with epicardial leads, mapping to determine the best pace site is a prerequisite. Pressure-volume loops offer real-time guidance for targeting epicardial lead placement during minimal invasive surgery.

Optimization of combination therapy of arsenic trioxide and fractionated radiotherapy for malignant glioma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ning Shoucheng; Knox, Susan J.

2006-06-01

Purpose: The primary objective was to optimize the combined treatment regimen using arsenic trioxide (ATO) and fractionated radiotherapy for the treatment of malignant glioma. Methods and Materials: Nude mice with human glioma xenograft tumors were treated with fractionated local tumor radiation of 250 cGy/fraction/day and 5 mg/kg ATO for 5-10 days. Results: Time course experiments demonstrated that maximal tumor growth delay occurred when ATO was administered between 0 and 4 h after radiation. The combination treatment of ATO and radiation synergistically inhibited tumor growth and produced a tumor growth delay time of 13.2 days, compared with 1.4 days and 6.5more » days for ATO and radiation alone (p < 0.01), respectively. The use of concurrent therapy of radiation and ATO initially, followed by ATO as maintenance therapy, was superior to the use of preloading with ATO before combined therapy and produced a tumor growth delay time of 22.7 days as compared with 11.7 days for the ATO preloading regimen (p < 0.01). The maintenance dose of ATO after concurrent therapy was effective and important for continued inhibition of tumor growth. Conclusions: The combined use of fractionated radiation and ATO is effective for the treatment of glioma xenograft tumors. ATO was most effective when administered 0-4 h after radiation without pretreatment with ATO. These results have important implications for the optimization of treatment regimen using ATO and fractionated radiotherapy for the treatment of brain tumors.« less

Rational Management of Iron-Deficiency Anaemia in Inflammatory Bowel Disease

PubMed Central

Vikner, Malene Elbaek; Weiss, Günter

2018-01-01

Anaemia is the most frequent, though often neglected, comorbidity of inflammatory bowel disease (IBD). Here we want to briefly present (1) the burden of anaemia in IBD, (2) its pathophysiology, which mostly arises from bleeding-associated iron deficiency, followed by (3) diagnostic evaluation of anaemia, (4) a balanced overview of the different modes of iron replacement therapy, (5) evidence for their therapeutic efficacy and subsequently, (6) an updated recommendation for the practical management of anaemia in IBD. Following the introduction of various intravenous iron preparations over the last decade, questions persist about when to use these preparations as opposed to traditional and other novel oral iron therapeutic agents. At present, oral iron therapy is generally preferred for patients with quiescent IBD and mild iron-deficiency anaemia. However, in patients with flaring IBD that hampers intestinal iron absorption and in those with inadequate responses to or side effects with oral preparations, intravenous iron supplementation is the therapy of choice, although information on the efficacy of intravenous iron in patients with active IBD and anaemia is scare. Importantly, anaemia in IBD is often multifactorial and a careful diagnostic workup is mandatory for optimized treatment. Nevertheless, limited information is available on optimal therapeutic start and end points for treatment of anaemia. Of note, neither oral nor intravenous therapies seem to exacerbate the clinical course of IBD. However, additional prospective studies are still warranted to determine the optimal therapy in complex conditions such as IBD. PMID:29342861

Challenges and unmet needs in basal insulin therapy: lessons from the Asian experience

PubMed Central

Chan, Wing Bun; Chen, Jung Fu; Goh, Su-Yen; Vu, Thi Thanh Huyen; Isip-Tan, Iris Thiele; Mudjanarko, Sony Wibisono; Bajpai, Shailendra; Mabunay, Maria Aileen; Bunnag, Pongamorn

2017-01-01

Basal insulin therapy can improve glycemic control in people with type 2 diabetes. However, timely initiation, optimal titration, and proper adherence to prescribed basal insulin regimens are necessary to achieve optimal glycemic control. Even so, glycemic control may remain suboptimal in a significant proportion of patients. Unique circumstances in Asia (eg, limited resources, management of diabetes primarily in nonspecialist settings, and patient populations that are predominantly less educated) coupled with the limitations of current basal insulin options (eg, risk of hypoglycemia and dosing time inflexibility) amplify the challenge of optimal basal insulin therapy in Asia. Significant progress has been made with long-acting insulin analogs (insulin glargine 100 units/mL and insulin detemir), which provide longer coverage and less risk of hypoglycemia over intermediate-acting insulin (Neutral Protamine Hagedorn insulin). Furthermore, recent clinical evidence suggests that newer long-acting insulin analogs, new insulin glargine 300 units/mL and insulin degludec, may address some of the unmet needs of current basal insulin options in terms of risk of hypoglycemia and dosing time inflexibility. Nevertheless, more can be done to overcome barriers to basal insulin therapy in Asia, through educating both patients and physicians, developing better patient support models, and improving accessibility to long-acting insulin analogs. In this study, we highlight the unique challenges associated with basal insulin therapy in Asia and, where possible, propose strategies to address the unmet needs by drawing on clinical experiences and perspectives in Asia. PMID:29276400

Challenges and unmet needs in basal insulin therapy: lessons from the Asian experience.

PubMed

Chan, Wing Bun; Chen, Jung Fu; Goh, Su-Yen; Vu, Thi Thanh Huyen; Isip-Tan, Iris Thiele; Mudjanarko, Sony Wibisono; Bajpai, Shailendra; Mabunay, Maria Aileen; Bunnag, Pongamorn

2017-01-01

Basal insulin therapy can improve glycemic control in people with type 2 diabetes. However, timely initiation, optimal titration, and proper adherence to prescribed basal insulin regimens are necessary to achieve optimal glycemic control. Even so, glycemic control may remain suboptimal in a significant proportion of patients. Unique circumstances in Asia (eg, limited resources, management of diabetes primarily in nonspecialist settings, and patient populations that are predominantly less educated) coupled with the limitations of current basal insulin options (eg, risk of hypoglycemia and dosing time inflexibility) amplify the challenge of optimal basal insulin therapy in Asia. Significant progress has been made with long-acting insulin analogs (insulin glargine 100 units/mL and insulin detemir), which provide longer coverage and less risk of hypoglycemia over intermediate-acting insulin (Neutral Protamine Hagedorn insulin). Furthermore, recent clinical evidence suggests that newer long-acting insulin analogs, new insulin glargine 300 units/mL and insulin degludec, may address some of the unmet needs of current basal insulin options in terms of risk of hypoglycemia and dosing time inflexibility. Nevertheless, more can be done to overcome barriers to basal insulin therapy in Asia, through educating both patients and physicians, developing better patient support models, and improving accessibility to long-acting insulin analogs. In this study, we highlight the unique challenges associated with basal insulin therapy in Asia and, where possible, propose strategies to address the unmet needs by drawing on clinical experiences and perspectives in Asia.

Virtual Reality Reflection Therapy Improves Balance and Gait in Patients with Chronic Stroke: Randomized Controlled Trials.

PubMed

In, Taesung; Lee, Kyeongjin; Song, Changho

2016-10-28

BACKGROUND Virtual reality reflection therapy (VRRT) is a technically enhanced version of the mirror therapy concept. The aim of this study was to investigate whether VRRT could improve the postural balance and gait ability of patients with chronic stroke. MATERIAL AND METHODS Twenty-five patients with chronic stroke were randomly allocated into the VRRT group (n=13) and the control group (n=12). The participants in both groups performed a conventional rehabilitation program for 30 minutes. The VRRT group also performed a VRRT program for 30 minutes, five times a week for 4 weeks. The control group performed conventional rehabilitation program and a placebo VRRT program. Outcome measures included Berg Balance Scale (BBS), the Functional Reaching Test (FRT), and the Timed Up and Go (TUG) test (for dynamic balance ability), postural sway (for static balance ability), and 10 meter walking velocity (10 mWV) for gait ability. RESULTS There were statistically significant improvements in the VRRT group compared with the control group for BBS, FRT, TUG, postural sway (mediolateral sway distance with eyes open and eyes closed, anteroposterior and total sway distance with eyes open but not with eyes closed), and 10 mWV (p<0.05). CONCLUSIONS Applying VRRT (even as a home treatment) along with a conventional rehabilitation program for patients with chronic stroke might be even more beneficial than conventional rehabilitation program alone in improving affected lower limb function. Future studies should investigate the effectiveness of VRRT with optimal patient selection, and duration and intensity of training.

Superficial Burn Wound Healing with Intermittent Negative Pressure Wound Therapy Under Limited Access and Conventional Dressings

PubMed Central

Honnegowda, Thittamaranahalli Muguregowda; Padmanabha Udupa, Echalasara Govindarama; Rao, Pragna; Kumar, Pramod; Singh, Rekha

2016-01-01

BACKGROUND Thermal injury is associated with several biochemical and histopathological alteration in tissue. Analysis of these objective parameters in research and clinical field are common to determine healing rate of burn wound. Negative pressure wound therapy has been achieved wide success in treating chronic wounds. This study determines superficial burn wound healing with intermittent negative pressure wound therapy under limited access and conventional dressings METHODS A total 50 patients were randomised into two equal groups: limited access and conventional dressing groups. Selective biochemical parameters such as hydroxyproline, hexosamine, total protein, and antioxidants, malondialdhyde (MDA), wound surface pH, matrix metalloproteinase-2 (MMP-2), and nitric oxide (NO) were measured in the granulation tissue. Histopathologically, necrotic tissue, amount of inflammatory infiltrate, angiogenesis and extracellular matrix deposition (ECM) were studied to determine wound healing under intermittent negative pressure. RESULTS Patients treated with limited access have shown significant increase in the mean hydroxyproline, hexosamine, total protein, reduced glutathione (GSH), glutathione peroxidase (GPx), and decrease in MDA, MMP-2, wound surface pH, and NO. Histopathologic study showed that there was a significant difference after 10 days of treatment between limited access vs conventional dressing group, Median (Q1, Q3)=3 (2, 4.25) vs 2 (1.75, 4). CONCLUSION Limited access was shown to exert its beneficial effects on wound healing by increasing ground substance, antioxidants and reducing MMP-2 activity, MDA, NO and providing optimal pH, decreasing necrotic tissue, amount of inflammatory infiltrate, increasing ECM deposition and angiogenesis. PMID:27853690

Threaded biliary inside stents are a safe and effective therapeutic option in cases of malignant hilar obstruction

PubMed Central

2013-01-01

Background Although endoscopic biliary stents have been accepted as part of palliative therapy for cases of malignant hilar obstruction, the optimal endoscopic management regime remains controversial. In this study, we evaluated the safety and efficacy of placing a threaded stent above the sphincter of Oddi (threaded inside plastic stents, threaded PS) and compared the results with those of other stent types. Methods Patients with malignant hilar obstruction, including those requiring biliary drainage for stent occlusion, were selected. Patients received either one of the following endoscopic indwelling stents: threaded PS, conventional plastic stents (conventional PS), or metallic stents (MS). Duration of stent patency and the incident of complication were compared in these patients. Results Forty-two patients underwent placement of endoscopic indwelling stents (threaded PS = 12, conventional PS = 17, MS = 13). The median duration of threaded PS patency was significantly longer than that of conventional PS patency (142 vs. 32 days; P = 0.04, logrank test). The median duration of threaded PS and MS patency was not significantly different (142 vs. 150 days, P = 0.83). Stent migration did not occur in any group. Among patients who underwent threaded PS placement as a salvage therapy after MS obstruction due to tumor ingrowth, the median duration of MS patency was significantly shorter than that of threaded PS patency (123 vs. 240 days). Conclusions Threaded PS are safe and effective in cases of malignant hilar obstruction; moreover, it is a suitable therapeutic option not only for initial drainage but also for salvage therapy. PMID:23410217

Negative argininosuccinate synthetase expression in melanoma tumours may predict clinical benefit from arginine-depleting therapy with pegylated arginine deiminase

PubMed Central

Feun, L G; Marini, A; Walker, G; Elgart, G; Moffat, F; Rodgers, S E; Wu, C J; You, M; Wangpaichitr, M; Kuo, M T; Sisson, W; Jungbluth, A A; Bomalaski, J; Savaraj, N

2012-01-01

Background: Arginine-depleting therapy with pegylated arginine deiminase (ADI-PEG20) was reported to have activity in advanced melanoma in early phase I–II trial, and clinical trials are currently underway in other cancers. However, the optimal patient population who benefit from this treatment is unknown. Methods: Advanced melanoma patients with accessible tumours had biopsy performed before the start of treatment with ADI-PEG20 and at the time of progression or relapse when amenable to determine whether argininosuccinate synthetase (ASS) expression in tumour was predictive of response to ADI-PEG20. Results: Twenty-seven of thirty-eight patients treated had melanoma tumours assessable for ASS staining before treatment. Clinical benefit rate (CBR) and longer time to progression were associated with negative expression of tumour ASS. Only 1 of 10 patients with ASS-positive tumours (ASS+) had stable disease, whereas 4 of 17 (24%) had partial response and 5 had stable disease, when ASS expression was negative (ASS−), giving CBR rates of 52.9 vs 10%, P=0.041. Two responding patients with negative ASS expression before therapy had rebiopsy after tumour progression and the ASS expression became positive. The survival of ASS− patients receiving at least four doses at 320 IU m−2 was significantly better than the ASS+ group at 26.5 vs 8.5 months, P=0.024. Conclusion: ADI-PEG20 is safe and the drug is only efficacious in melanoma patients whose tumour has negative ASS expression. Argininosuccinate synthetase tumour positivity is associated with drug resistance and tumour progression. PMID:22472884

Guidelines for the prevention and treatment of travelers’ diarrhea: a graded expert panel report

PubMed Central

Beeching, Nicholas J.; DuPont, Herbert L.; Hamer, Davidson H.; Kozarsky, Phyllis; Libman, Michael; Steffen, Robert; Taylor, David; Tribble, David R.; Vila, Jordi; Zanger, Philipp; Ericsson, Charles D.

2017-01-01

Abstract Background: Travelers’ diarrhea causes significant morbidity including some sequelae, lost travel time and opportunity cost to both travelers and countries receiving travelers. Effective prevention and treatment are needed to reduce these negative impacts. Methods: This critical appraisal of the literature and expert consensus guideline development effort asked several key questions related to antibiotic and non-antibiotic prophylaxis and treatment, utility of available diagnostics, impact of multi-drug resistant (MDR) colonization associated with travel and travelers’ diarrhea, and how our understanding of the gastrointestinal microbiome should influence current practice and future research. Studies related to these key clinical areas were assessed for relevance and quality. Based on this critical appraisal, guidelines were developed and voted on using current standards for clinical guideline development methodology. Results: New definitions for severity of travelers’ diarrhea were developed. A total of 20 graded recommendations on the topics of prophylaxis, diagnosis, therapy and follow-up were developed. In addition, three non-graded consensus-based statements were adopted. Conclusions: Prevention and treatment of travelers’ diarrhea requires action at the provider, traveler and research community levels. Strong evidence supports the effectiveness of antimicrobial therapy in most cases of moderate to severe travelers’ diarrhea, while either increasing intake of fluids only or loperamide or bismuth subsalicylate may suffice for most cases of mild diarrhea. Further studies are needed to address knowledge gaps regarding optimal therapies, the individual, community and global health risks of MDR acquisition, manipulation of the microbiome in prevention and treatment and the utility of laboratory testing in returning travelers with persistent diarrhea. PMID:28521004

Virtual Reality Reflection Therapy Improves Balance and Gait in Patients with Chronic Stroke: Randomized Controlled Trials

PubMed Central

In, Taesung; Lee, Kyeongjin; Song, Changho

2016-01-01

Background Virtual reality reflection therapy (VRRT) is a technically enhanced version of the mirror therapy concept. The aim of this study was to investigate whether VRRT could improve the postural balance and gait ability of patients with chronic stroke. Material/Methods Twenty-five patients with chronic stroke were randomly allocated into the VRRT group (n=13) and the control group (n=12). The participants in both groups performed a conventional rehabilitation program for 30 minutes. The VRRT group also performed a VRRT program for 30 minutes, five times a week for 4 weeks. The control group performed conventional rehabilitation program and a placebo VRRT program. Outcome measures included Berg Balance Scale (BBS), the Functional Reaching Test (FRT), and the Timed Up and Go (TUG) test (for dynamic balance ability), postural sway (for static balance ability), and 10 meter walking velocity (10 mWV) for gait ability. Results There were statistically significant improvements in the VRRT group compared with the control group for BBS, FRT, TUG, postural sway (mediolateral sway distance with eyes open and eyes closed, anteroposterior and total sway distance with eyes open but not with eyes closed), and 10 mWV (p<0.05). Conclusions Applying VRRT (even as a home treatment) along with a conventional rehabilitation program for patients with chronic stroke might be even more beneficial than conventional rehabilitation program alone in improving affected lower limb function. Future studies should investigate the effectiveness of VRRT with optimal patient selection, and duration and intensity of training. PMID:27791207

Cancer treatment as a game: integrating evolutionary game theory into the optimal control of chemotherapy

NASA Astrophysics Data System (ADS)

Orlando, Paul A.; Gatenby, Robert A.; Brown, Joel S.

2012-12-01

Chemotherapy for metastatic cancer commonly fails due to evolution of drug resistance in tumor cells. Here, we view cancer treatment as a game in which the oncologists choose a therapy and tumors ‘choose’ an adaptive strategy. We propose the oncologist can gain an upper hand in the game by choosing treatment strategies that anticipate the adaptations of the tumor. In particular, we examine the potential benefit of exploiting evolutionary tradeoffs in tumor adaptations to therapy. We analyze a math model where cancer cells face tradeoffs in allocation of resistance to two drugs. The tumor ‘chooses’ its strategy by natural selection and the oncologist chooses her strategy by solving a control problem. We find that when tumor cells perform best by investing resources to maximize response to one drug the optimal therapy is a time-invariant delivery of both drugs simultaneously. However, if cancer cells perform better using a generalist strategy allowing resistance to both drugs simultaneously, then the optimal protocol is a time varying solution in which the two drug concentrations negatively covary. However, drug interactions can significantly alter these results. We conclude that knowledge of both evolutionary tradeoffs and drug interactions is crucial in planning optimal chemotherapy schedules for individual patients.

Optimization and evaluation of lipid emulsions for intravenous co-delivery of artemether and lumefantrine in severe malaria treatment.

PubMed

Yang, Yinxian; Gao, Hailing; Zhou, Shuang; Kuang, Xiao; Wang, Zhenjie; Liu, Hongzhuo; Sun, Jin

2018-05-10

Parenteral therapy for severe and complicated malaria is necessary, but currently available parenteral antimalarials have their own drawbacks. As for recommended artemisinin-based combination therapy, antimalarial artemether and lumefantrine are limited in parenteral delivery due to their poor water solubility. Herein, the aim of this study was to develop the lipid-based emulsions for intravenous co-delivery of artemether and lumefantrine. The lipid emulsion was prepared by high-speed shear and high-pressure homogenization, and the formulations were optimized mainly by monitoring particle size distribution under autoclaved conditions. The final optimal formulation was with uniform particle size distribution (~ 220 nm), high encapsulation efficiency (~ 99%), good physiochemical stability, and acceptable hemolysis potential. The pharmacokinetic study in rats showed that C max of artemether and lumefantrine for the optimized lipid emulsions were significantly increased than the injectable solution, which was critical for rapid antimalarial activity. Furthermore, the AUC 0-t of artemether and lumefantrine in the lipid emulsion group were 5.01- and 1.39-fold of those from the solution, respectively, suggesting enhanced bioavailability. With these findings, the developed lipid emulsion is a promising alternative parenteral therapy for the malaria treatment, especially for severe or complicated malaria.

Safinamide as Add-On Therapy to Levodopa in Mid- to Late-Stage Parkinson’s Disease Fluctuating Patients: Post hoc Analysesof Studies 016 and SETTLE

PubMed Central

Cattaneo, Carlo; Sardina, Marco; Bonizzoni, Ermino

2016-01-01

Background: Studies 016 and SETTLE showed that safinamide was safe and effective as adjunct therapy in patients with advanced Parkinson’s disease (PD) and motor fluctuations. The addition of safinamide to a stable dose of levodopa alone or with other antiparkinsonian medications significantly increased ON time with no/non-troublesome dyskinesia, decreased OFF time and improved Parkinson’s symptoms. Objective: To evaluate the clinical effects of safinamide 100 mg/day on motor fluctuations and cardinal Parkinson’s symptoms in specific patient subgroups using pooled data from Studies 016 and SETTLE. Methods: Both studies were double blind, placebo-controlled, randomized, phase 3 trials which enrolled patients with mid- to late-stage PD experiencing motor fluctuations while receiving optimized and stable doses of levodopa, alone or with other dopaminergic treatments. The present post-hoc analyses assessed the change from baseline in ON time (with no or non-troublesome dyskinesia) and OFF time in subgroups of patients who were receiving only levodopa at baseline, who were classified as “mild fluctuators” (daily OFF time ≤4 h), and who were receiving concomitant dopaminergic therapy, with or without amantadine, and the effects of safinamide versus placebo on individual cardinal PD symptoms during ON time. Results: Safinamide significantly increased mean ON time (with no or non-troublesome dyskinesia) and reduced mean OFF time when used as first adjunct therapy in levodopa-treated patients and patients with mild motor fluctuations. Mean daily ON time (with no or non-troublesome dyskinesia) and OFF time were favorably changed, compared with placebo, to similar extents regardless of whether patients were receiving concomitant dopamine agonists, catechol-O-methyltransferase inhibitors and amantadine. Additionally, safinamide improved bradykinesia, rigidity, tremor and gait. Conclusions: Safinamide was a safe and effective first adjunct therapy in levodopa-treated patients and improved 4/5 cardinal symptoms of PD while providing benefits to mild and non-mild fluctuators and patients receiving other concomitant dopaminergic therapies. PMID:26889632

Maximizing Exposure Therapy: An Inhibitory Learning Approach

PubMed Central

Craske, Michelle G.; Treanor, Michael; Conway, Chris; Zbozinek, Tomislav; Vervliet, Bram

2014-01-01

Exposure therapy is an effective approach for treating anxiety disorders, although a substantial number of individuals fail to benefit or experience a return of fear after treatment. Research suggests that anxious individuals show deficits in the mechanisms believed to underlie exposure therapy, such as inhibitory learning. Targeting these processes may help improve the efficacy of exposure-based procedures. Although evidence supports an inhibitory learning model of extinction, there has been little discussion of how to implement this model in clinical practice. The primary aim of this paper is to provide examples to clinicians for how to apply this model to optimize exposure therapy with anxious clients, in ways that distinguish it from a ‘fear habituation’ approach and ‘belief disconfirmation’ approach within standard cognitive-behavior therapy. Exposure optimization strategies include 1) expectancy violation, 2) deepened extinction, 3) occasional reinforced extinction, 4) removal of safety signals, 5) variability, 6) retrieval cues, 7) multiple contexts, and 8) affect labeling. Case studies illustrate methods of applying these techniques with a variety of anxiety disorders, including obsessive-compulsive disorder, posttraumatic stress disorder, social phobia, specific phobia, and panic disorder. PMID:24864005

Topology Optimization of an Aircraft Wing

DTIC Science & Technology

2015-06-11

Fraction VWT Virtual Wind Tunnel xvi TOPOLOGY OPTIMIZATION OF AN AIRCRAFT WING I. Introduction 1.1 Background Current aircraft wing design , which...ware in order to optimize the design of individual spars and wing-box structures for large commercial aircraft . They considered a hybrid global/local...weight in an aircraft by eliminating unnecessary material. An optimized approach has the potential to streamline the design process by allowing a

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

PubMed

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 < 0.05). The MMP-9/MMP-2 ratio increased at 14 days after the 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 clinical application.

Feminist Therapy with Mainland Puerto Rican Women.

ERIC Educational Resources Information Center

Comas-Diaz, Lillian

1987-01-01

Discusses the use of feminist therapy with mainland Puerto Rican women, presenting clinical vignettes. Emphasizes the consideration of sociocultural context, including the experience of cross-cultural translocation, transculturation, the colonial background of Puerto Rico, Puerto Rican sex roles, power issues and Puertorriquenas' sense of…

Feminist Therapy with Ethnic Minority Women.

ERIC Educational Resources Information Center

Sieber, Jindra A.; Cairns, Kathleen V.

1991-01-01

Asserts that feminist assumptions about nature, process, and goals of therapy make feminist counseling particularly effective approach for women from diverse racial and cultural backgrounds. Considers feminist interpretation of women's problems from social, political, and economic perspectives to be particularly relevant to experiences and…

Physical therapies for Achilles tendinopathy: systematic review and meta-analysis

PubMed Central

2012-01-01

Background Achilles tendinopathy (AT) is a common condition, causing considerable morbidity in athletes and non-athletes alike. Conservative or physical therapies are accepted as first-line management of AT; however, despite a growing volume of research, there remains a lack of high quality studies evaluating their efficacy. Previous systematic reviews provide preliminary evidence for non-surgical interventions for AT, but lack key quality components as outlined in the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) Statement. The aim of this study was to conduct a systematic review and meta-analysis (where possible) of the evidence for physical therapies for AT management. Methods A comprehensive strategy was used to search 11 electronic databases from inception to September 2011. Search terms included Achilles, tendinopathy, pain, physical therapies, electrotherapy and exercise (English language full-text publications, human studies). Reference lists of eligible papers were hand-searched. Randomised controlled trials (RCTs) were included if they evaluated at least one non-pharmacological, non-surgical intervention for AT using at least one outcome of pain and/or function. Two independent reviewers screened 2852 search results, identifying 23 suitable studies, and assessed methodological quality and risk of bias using a modified PEDro scale. Effect size calculation and meta-analyses were based on fixed and random effects models respectively. Results Methodological quality ranged from 2 to 12 (/14). Four studies were excluded due to high risk of bias, leaving 19 studies, the majority of which evaluated midportion AT. Effect sizes from individual RCTs support the use of eccentric exercise. Meta-analyses identified significant effects favouring the addition of laser therapy to eccentric exercise at 12 weeks (pain VAS: standardised mean difference −0.59, 95% confidence interval −1.11 to −0.07), as well as no differences in effect between eccentric exercise and shock wave therapy at 16 weeks (VISA-A:–0.55,–2.21 to 1.11). Pooled data did not support the addition of night splints to eccentric exercise at 12 weeks (VISA-A:–0.35,–1.44 to 0.74). Limited evidence from an individual RCT suggests microcurrent therapy to be an effective intervention. Conclusions Practitioners can consider eccentric exercise as an initial intervention for AT, with the addition of laser therapy as appropriate. Shock wave therapy may represent an effective alternative. High-quality RCTs following CONSORT guidelines are required to further evaluate the efficacy of physical therapies and determine optimal clinical pathways for AT. PMID:22747701

DOE Office of Scientific and Technical Information (OSTI.GOV)

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

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

Optimal nutrition therapy in paediatric critical care in the Asia-Pacific and Middle East: a consensus.

PubMed

Lee, Jan Hau; Rogers, Elizabeth; Chor, Yek Kee; Samransamruajkit, Rujipat; Koh, Pei Lin; Miqdady, Mohamad; Al-Mehaidib, Ali Ibrahim; Pudjiadi, Antonius; Singhi, Sunit; Mehta, Nilesh M

2016-12-01

Current practices and available resources for nutrition therapy in paediatric intensive care units (PICUs) in the Asia Pacific-Middle East region are expected to differ from western countries. Existing guidelines for nutrition management in critically ill children may not be directly applicable in this region. This paper outlines consensus statements developed by the Asia Pacific-Middle East Consensus Working Group on Nutrition Therapy in the Paediatric Critical Care Environment. Challenges and recommendations unique to the region are described. Following a systematic literature search from 2004-2014, consensus statements were developed for key areas of nutrient delivery in the PICU. This review focused on evidence applicable to the Asia Pacific-Middle East region. Quality of evidence and strength of recommendations were rated according to the Grading of Recommendation Assessment, Development and Evaluation approach. Enteral nutrition (EN) is the preferred mode of nutritional support. Feeding algorithms that optimize EN should be encouraged and must include: assessment and monitoring of nutritional status, selection of feeding route, time to initiate and advance EN, management strategies for EN intolerance and indications for using parenteral nutrition (PN). Despite heterogeneity in nutritional status of patients, availability of resources and diversity of cultures, PICUs in the region should consider involvement of dieticians and/or nutritional support teams. Robust evidence for several aspects of optimal nutrition therapy in PICUs is lacking. Nutritional assessment must be implemented to document prevalence and impact of malnutrition. Nutritional support must be given greater priority in PICUs, with particular emphasis in optimizing EN delivery.

Adherence to medication under mandatory and voluntary mail benefit designs.

PubMed

Liberman, Joshua N; Hutchins, David S; Shrank, Will H; Slezak, Julie; Brennan, Troyen A

2011-07-01

To compare adherence rates under voluntary and mandatory mail benefit designs. Matched retrospective cohort. Adherence rates in the first year of therapy were compared between voluntary and mandatory mail cohorts composed of individuals who initiated statin, angiotensin-converting enzyme (ACE) inhibitor, angiotensin receptor blocker (ARB), platelet aggregation inhibitor, metformin, glitazone, or sulfonylurea therapy at a retail pharmacy between January 1 and March 31, 2009. Initiators in mandatory mail plans were matched on therapeutic class, age, sex, prospective risk, and cost of initial prescription with those in voluntary mail plans. Logistic regression models of optimal adherence were constructed to adjust for measured confounders. Persistence rates were similar through the first 60 days of therapy. The mandatory mail cohort had a notable drop in persistence by day 90 (63.3% vs 56.3%, P <.001), with a more pronounced drop among those without previous mail-service pharmacy use (50.5%). Median medication possession ratio (49.2% vs 57.4%) and optimal adherence (33.6% vs 36.1) were also lower. In the multivariable models, mandatory mail participants were less likely to achieve optimal adherence overall (odds ratio [OR] 0.70; 95% confidence interval [CI] 0.67-0.74) and in the metformin (OR 0.55), sulfonylurea (OR 0.72), ACE inhibitor (OR 0.74), ARB (OR 0.69), and statin (OR 0.69) classes. Participants with no prior use of mail-service pharmacy had significantly lower odds of achieving optimal adherence in all therapeutic classes. Mandatory mail appears to cause some members to discontinue therapy prematurely, particularly those without previous mail service pharmacy experience.

[Baseline characteristics and changes in treatment after a period of optimization of the patients included in the study EFICAR].

PubMed

Gómez-Marcos, Manuel A; Agudo-Conde, Cristina; Torcal, Jesús; Echevarria, Pilar; Domingo, Mar; Arietaleanizbeascoa, María; Sanz-Guinea, Aitor; de la Torre, Maria M; Ramírez, Jose I; García-Ortiz, Luis

2016-03-01

To describe the baseline date and drugs therapy changes during treatment optimization in patients with heart failure with depressed systolic function included in the EFICAR study. Multicenter randomized clinical trial. Seven Health Centers. 150 patients (ICFSD) age 68±10 years, 77% male. Sociodemographic variables, comorbidities (Charlson index), functional capacity and quality of life. Drug therapy optimization was performed. The main etiology was ischemic heart disease (45%), with 89% in functional class II. The Charlson index was 2.03±1.05. The ejection fraction mean was 37%±8, 19% with ejection fraction <30%. With the stress test 6.3±1.6 mean was reached, with the 6 minutes test 446±78 meters and the chair test 13.7±4.4 seconds. The overall quality of life with ejection fraction was 22.8±18.7 and with the Short Form-36 Health Survey, physical health 43.3±8.4 and mental health 50.1±10.6. After optimizing the treatment, the percentage of patients on drugs therapy and the dose of angiotensin converting enzyme inhibitors, angiotensin II receptor antagonists and beta-blockers were not changed. The majority of the subjects are in functional class II, with functional capacity and quality of life decreased and comorbidity index high. A protocolized drug therapy adjustment did not increase the dose or number of patients with effective drugs for heart failure with depressed systolic function. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.

New Therapies in Head and Neck Cancer.

PubMed

Santuray, Rodell T; Johnson, Daniel E; Grandis, Jennifer R

2018-05-01

Head and neck squamous cell carcinoma (HNSCC) is a common malignancy with high rates of mortality and morbidity. Beginning with cetuximab, investigators continue to optimize antibody technology to target cell-surface receptors that promote HNSCC growth. Small molecules and oligonucleotides have also emerged as therapeutic inhibitors of key receptor-mediated signaling pathways. Although many such therapies have been disappointing in clinical trials as single agents, they continue to be studied in combination with standard therapies. Approvals of pembrolizumab and nivolumab opened a new era of immunotherapy that aims to stimulate antitumor immunity in the tumor microenvironment. Immunotherapies are being intensively investigated in new HNSCC clinical trials, with the goal of optimizing the therapeutic potential of this new class of anticancer agent. Copyright © 2018 Elsevier Inc. All rights reserved.

Two is better than one; toward a rational design of combinatorial therapy.

PubMed

Chen, Sheng-Hong; Lahav, Galit

2016-12-01

Drug combination is an appealing strategy for combating the heterogeneity of tumors and evolution of drug resistance. However, the rationale underlying combinatorial therapy is often not well established due to lack of understandings of the specific pathways responding to the drugs, and their temporal dynamics following each treatment. Here we present several emerging trends in harnessing properties of biological systems for the optimal design of drug combinations, including the type of drugs, specific concentration, sequence of addition and the temporal schedule of treatments. We highlight recent studies showing different approaches for efficient design of drug combinations including single-cell signaling dynamics, adaption and pathway crosstalk. Finally, we discuss novel and feasible approaches that can facilitate the optimal design of combinatorial therapy. Copyright © 2016 Elsevier Ltd. All rights reserved.

The Application of Optimal Defaults to Improve Elementary School Lunch Selections: Proof of Concept

ERIC Educational Resources Information Center

Loeb, Katharine L.; Radnitz, Cynthia; Keller, Kathleen L.; Schwartz, Marlene B.; Zucker, Nancy; Marcus, Sue; Pierson, Richard N.; Shannon, Michael; DeLaurentis, Danielle

2018-01-01

Background: In this study, we applied behavioral economics to optimize elementary school lunch choices via parent-driven decisions. Specifically, this experiment tested an optimal defaults paradigm, examining whether strategically manipulating the health value of a default menu could be co-opted to improve school-based lunch selections. Methods:…

Immunomodulation to Optimize Vascularized Composite Allograft Integration in Limb Loss Therapy

DTIC Science & Technology

2014-10-01

AD_________________ Award Number: W81XWH-12-2-0058 TITLE: Immunomodulation to Optimize Vascularized...ADDRESS. 1. REPORT DATE October 2014 2. REPORT TYPE Annual 3. DATES COVERED 30 Sep 2013 - 29 Sep 2014 4. TITLE AND SUBTITLE Immunomodulation to...efficacious immunomodulation regimen based on belatacept to optimize the integration of limb transplantation after limb loss. Regulatory Review

Child Speech, Language and Communication Need Re-Examined in a Public Health Context: A New Direction for the Speech and Language Therapy Profession

ERIC Educational Resources Information Center

Law, James; Reilly, Sheena; Snow, Pamela C.

2013-01-01

Background: Historically speech and language therapy services for children have been framed within a rehabilitative framework with explicit assumptions made about providing therapy to individuals. While this is clearly important in many cases, we argue that this model needs revisiting for a number of reasons. First, our understanding of the nature…

On the Role of Dopamine Replacement Therapy in Decision-Making, Working Memory, and Reward in Parkinson's Disease: Does the Therapy-Dose Matter?

ERIC Educational Resources Information Center

Torta, Diana Maria Elena; Castelli, Lorys; Zibetti, Maurizio; Lopiano, Leonardo; Geminiani, Giuliano

2009-01-01

Background: Dopaminergic therapy proved to ameliorate motor deficits in Parkinson's disease but its effects on behavior and cognition vary according to factors that include, among others, the evolution of the disease and the nature of the task that is tested. This study addressed the question of whether, in moderate to advanced Parkinson's disease…

Direct versus Indirect and Individual versus Group Modes of Language Therapy for Children with Primary Language Impairment: Principal Outcomes from a Randomized Controlled Trial and Economic Evaluation

ERIC Educational Resources Information Center

Boyle, James M.; McCartney, Elspeth; O'Hare, Anne; Forbes, John

2009-01-01

Background: Many school-age children with language impairments are enrolled in mainstream schools and receive indirect language therapy, but there have been, to the authors' knowledge, no previous controlled studies comparing the outcomes and costs of direct and indirect intervention delivered by qualified therapists and therapy assistants, and…

Simple automatic strategy for background drift correction in chromatographic data analysis.

PubMed

Fu, Hai-Yan; Li, He-Dong; Yu, Yong-Jie; Wang, Bing; Lu, Peng; Cui, Hua-Peng; Liu, Ping-Ping; She, Yuan-Bin

2016-06-03

Chromatographic background drift correction, which influences peak detection and time shift alignment results, is a critical stage in chromatographic data analysis. In this study, an automatic background drift correction methodology was developed. Local minimum values in a chromatogram were initially detected and organized as a new baseline vector. Iterative optimization was then employed to recognize outliers, which belong to the chromatographic peaks, in this vector, and update the outliers in the baseline until convergence. The optimized baseline vector was finally expanded into the original chromatogram, and linear interpolation was employed to estimate background drift in the chromatogram. The principle underlying the proposed method was confirmed using a complex gas chromatographic dataset. Finally, the proposed approach was applied to eliminate background drift in liquid chromatography quadrupole time-of-flight samples used in the metabolic study of Escherichia coli samples. The proposed method was comparable with three classical techniques: morphological weighted penalized least squares, moving window minimum value strategy and background drift correction by orthogonal subspace projection. The proposed method allows almost automatic implementation of background drift correction, which is convenient for practical use. Copyright © 2016 Elsevier B.V. All rights reserved.

Relevant factors for the optimal duration of extended endocrine therapy in early breast cancer.

PubMed

Blok, Erik J; Kroep, Judith R; Meershoek-Klein Kranenbarg, Elma; Duijm-de Carpentier, Marjolijn; Putter, Hein; Liefers, Gerrit-Jan; Nortier, Johan W R; Rutgers, Emiel J Th; Seynaeve, Caroline M; van de Velde, Cornelis J H

2018-04-01

For postmenopausal patients with hormone receptor-positive early breast cancer, the optimal subgroup and duration of extended endocrine therapy is not clear yet. The aim of this study using the IDEAL patient cohort was to identify a subgroup for which longer (5 years) extended therapy is beneficial over shorter (2.5 years) extended endocrine therapy. In the IDEAL trial, 1824 patients who completed 5 years of adjuvant endocrine therapy (either 5 years of tamoxifen (12%), 5 years of an AI (29%), or a sequential strategy of both (59%)) were randomized between either 2.5 or 5 years of extended letrozole. For each prior therapy subgroup, the value of longer therapy was assessed for both node-negative and node-positive patients using Kaplan Meier and Cox regression survival analyses. In node-positive patients, there was a significant benefit of 5 years (over 2.5 years) of extended therapy (disease-free survival (DFS) HR 0.67, p = 0.03, 95% CI 0.47-0.96). This effect was only observed in patients who were treated initially with a sequential scheme (DFS HR 0.60, p = 0.03, 95% CI 0.38-0.95). In all other subgroups, there was no significant benefit of longer extended therapy. Similar results were found in patients who were randomized for their initial adjuvant therapy in the TEAM trial (DFS HR 0.37, p = 0.07, 95% CI 0.13-1.06), although this additional analysis was underpowered for definite conclusions. This study suggests that node-positive patients could benefit from longer extended endocrine therapy, although this effect appears isolated to patients treated with sequential endocrine therapy during the first 5 years and needs validation and long-term follow-up.

Optimizing Timing of Immunotherapy Improves Control of Tumors by Hypofractionated Radiation Therapy

PubMed Central

Baird, Jason R.; Savage, Talicia; Cottam, Benjamin; Friedman, David; Bambina, Shelly; Messenheimer, David J.; Fox, Bernard; Newell, Pippa; Bahjat, Keith S.; Gough, Michael J.; Crittenden, Marka R.

2016-01-01

The anecdotal reports of promising results seen with immunotherapy and radiation in advanced malignancies have prompted several trials combining immunotherapy and radiation. However, the ideal timing of immunotherapy with radiation has not been clarified. Tumor bearing mice were treated with 20Gy radiation delivered only to the tumor combined with either anti-CTLA4 antibody or anti-OX40 agonist antibody. Immunotherapy was delivered at a single timepoint around radiation. Surprisingly, the optimal timing of these therapies varied. Anti-CTLA4 was most effective when given prior to radiation therapy, in part due to regulatory T cell depletion. Administration of anti-OX40 agonist antibody was optimal when delivered one day following radiation during the post-radiation window of increased antigen presentation. Combination treatment of anti-CTLA4, radiation, and anti-OX40 using the ideal timing in a transplanted spontaneous mammary tumor model demonstrated tumor cures. These data demonstrate that the combination of immunotherapy and radiation results in improved therapeutic efficacy, and that the ideal timing of administration with radiation is dependent on the mechanism of action of the immunotherapy utilized. PMID:27281029

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

PubMed

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

2017-11-01

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

Making it stick: chasing the optimal stem cells for cardiac regeneration

PubMed Central

Quijada, Pearl; Sussman, Mark A

2014-01-01

Despite the increasing use of stem cells for regenerative-based cardiac therapy, the optimal stem cell population(s) remains in a cloud of uncertainty. In the past decade, the field has witnessed a surge of researchers discovering stem cell populations reported to directly and/or indirectly contribute to cardiac regeneration through processes of cardiomyogenic commitment and/or release of cardioprotective paracrine factors. This review centers upon defining basic biological characteristics of stem cells used for sustaining cardiac integrity during disease and maintenance of communication between the cardiac environment and stem cells. Given the limited successes achieved so far in regenerative therapy, the future requires development of unprecedented concepts involving combinatorial approaches to create and deliver the optimal stem cell(s) that will enhance myocardial healing. PMID:25340282

Optimizing countershading camouflage.

PubMed

Cuthill, Innes C; Sanghera, N Simon; Penacchio, Olivier; Lovell, Paul George; Ruxton, Graeme D; Harris, Julie M

2016-11-15

Countershading, the widespread tendency of animals to be darker on the side that receives strongest illumination, has classically been explained as an adaptation for camouflage: obliterating cues to 3D shape and enhancing background matching. However, there have only been two quantitative tests of whether the patterns observed in different species match the optimal shading to obliterate 3D cues, and no tests of whether optimal countershading actually improves concealment or survival. We use a mathematical model of the light field to predict the optimal countershading for concealment that is specific to the light environment and then test this prediction with correspondingly patterned model "caterpillars" exposed to avian predation in the field. We show that the optimal countershading is strongly illumination-dependent. A relatively sharp transition in surface patterning from dark to light is only optimal under direct solar illumination; if there is diffuse illumination from cloudy skies or shade, the pattern provides no advantage over homogeneous background-matching coloration. Conversely, a smoother gradation between dark and light is optimal under cloudy skies or shade. The demonstration of these illumination-dependent effects of different countershading patterns on predation risk strongly supports the comparative evidence showing that the type of countershading varies with light environment.

Fluid therapy in vomiting and diarrhea.

PubMed

Brown, Andrew J; Otto, Cynthia M

2008-05-01

Fluid therapy in the patient with vomiting and diarrhea is essential to correct hypovolemia, dehydration, acid-base imbalance, and serum electrolyte abnormalities. Prediction of acid-base or electrolyte disturbances is difficult; therefore, point of care testing is beneficial to optimize therapy. This article focuses on the pathophysiology and treatment of hypovolemia, dehydration, electrolyte disturbances, and acid-base derangements resulting from and associated with vomiting and diarrhea.

TARGETED THERAPY: Generic imatinib — impact on frontline and salvage therapy for CML

PubMed Central

Gorkin, Larry; Kantarjian, Hagop

2017-01-01

Imatinib has revolutionized the treatment of chronic myeloid leukaemia (CML). In 2016, generic imatinib will be introduced into the US market. We analyse the potential impact of this new product on patient care and optimal CML therapy, and comment on the effect that distorted cancer drug pricing in the USA will have on treatment for patients with limited therapeutic options. PMID:27098218

Occupational Therapy for School-Aged Children in India

ERIC Educational Resources Information Center

Asher, Asha; Jatar, Anuradha; Bijlani, Jyothika

2015-01-01

Occupational therapists exploring international opportunities should understand how the profession is practiced globally. This paper describes the framework under which occupational therapy services can be accessed by families of children with disabilities in urban India. Background information about the country, its health care, and occupational…

Helping Individuals with Sleep Disturbances: Some Behavior Therapy Techniques.

ERIC Educational Resources Information Center

Alley, Patricia M.

1983-01-01

Describes a range of behavior therapy techniques for treating sleep disturbances, including physical activity, relaxation training, biofeedback, autogenic training, and cognitive techniques. The importance of understanding the client's background is emphasized. Restoring the client's self-control and positive psychological growth are stressed.…

Physical therapy and occupational therapy in Parkinson's disease.

PubMed

Radder, Danique L M; Sturkenboom, Ingrid H; van Nimwegen, Marlies; Keus, Samyra H; Bloem, Bastiaan R; de Vries, Nienke M

2017-10-01

Current medical management is only partially effective in controlling the symptoms of Parkinson's disease. As part of comprehensive multidisciplinary care, physical therapy and occupational therapy aim to support people with Parkinson's disease in dealing with the consequences of their disease in daily activities. In this narrative review, we address the limitations that people with Parkinson's disease may encounter despite optimal medical management, and we clarify both the unique and shared approaches that physical therapists and occupational therapists can apply in treating these limitations.

Improved outcome with early rifampicin combination treatment in methicillin-sensitive Staphylococcus aureus bacteraemia with a deep infection focus - a retrospective cohort study.

PubMed

Forsblom, Erik; Ruotsalainen, Eeva; Järvinen, Asko

2015-01-01

Rifampicin has been used as adjunctive therapy in Staphylococcus aureus bacteraemia (SAB) with a deep infection focus. However, data for prognostic impact of rifampicin therapy is unestablished including the optimal initiation time point. We studied the impact of rifampicin therapy and the optimal initiation time for rifampicin treatment on prognosis in methicillin-sensitive S. aureus bacteraemia with a deep infection. Retrospective, multicentre study in Finland including 357 SAB patients with a deep infection focus. Patients with alcoholism, liver disease or patients who died within 3 days were excluded. Patients were categorised according to duration of rifampicin therapy and according to whether rifampicin was initiated early (within 7 days) or late (7 days after) after the positive blood cultures. Primary end point was 90 days mortality. Twenty-seven percent of patients received no rifampicin therapy, 14% received rifampicin for 1-13 days whereas 59% received rifampicin ≥14 days. The 90 day mortality was; 26% for patients treated without rifampicin, 16% for rifampicin therapy of any length and 10% for early onset rifampicin therapy ≥14 days. Lack of rifampicin therapy increased (OR 1.89, p=0.026), rifampicin of any duration decreased (OR 0.53, p=0.026) and rifampicin therapy ≥14 days with early onset lowered the risk for a fatal outcome (OR 0.33, p<0.01) during 90 days follow-up. Rifampicin adjunctive therapy for at least 14 days and initiated within 7 days of positive blood culture associated with improved outcome among SAB patients with a deep infection.

SU-F-T-163: Improve Proton Therapy Efficiency: Report of a Workshop

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zheng, Y; Flanz, J; Mah, D

Purpose: The technology of proton therapy, especially the pencil beam scanning technique, is evolving very quickly. However, the efficiency of proton therapy seems to lag behind conventional photon therapy. The purpose of the abstract is to report on the findings of a workshop on improvement of QA, planning and treatment efficiency in proton therapy. Methods: A panel of physicists, clinicians, and vendor representatives from over 18 institutions in the United States and internationally were convened in Knoxville, Tennessee in November, 2015. The panel discussed several topics on how to improve proton therapy efficiency, including 1) lean principle and failure modemore » and effects analysis, 2) commissioning and machine QA, 3) treatment planning, optimization and evaluation, 4) patient positioning and IGRT, 5) vendor liaison and machine availability, and 6) staffing, education and training. Results: The relative time needed for machine QA, treatment planning & check in proton therapy was found to range from 1 to 2.5 times of that in photon therapy. Current status in proton QA, planning and treatment was assessed. Key areas for efficiency improvement, such as elimination of unnecessary QA items or steps and development of efficient software or hardware tools, were identified. A white paper to summarize our findings is being written. Conclusion: It is critical to improve efficiency by developing reliable proton beam lines, efficient software tools on treatment planning, optimization and evaluation, and dedicated proton QA device. Conscious efforts and collaborations from both industry leaders and proton therapy centers are needed to achieve this goal and further advance the technology of proton therapy.« less

Implications for managed care and specialty pharmacy in rheumatoid arthritis.

PubMed

Cardarelli, William J

2012-12-01

Treatment of rheumatoid arthritis (RA) can be very costly. Cost-effectiveness studies provide insight into the value of treatment from a number of perspectives (eg, societal, healthcare). In most cases, the indirect costs of RA can offset the direct costs in 2 ways. Prevention of disease progression can limit future costs, such as those related to surgery and hospitalization. When disease progression is minimized, patients feel better and can have improved work productivity. Disease control of RA has improved over time, and this is attributed primarily to the introduction of more effective therapies. Despite the effectiveness of new therapies, there are a number of barriers to optimal treatment. Barriers include lack of education for patients and practitioners about RA, poor patient-provider communication, uncertainty regarding which treatments to choose, cost, and lack of adherence. Specialty pharmacy and disease therapy management programs can assist patients by providing structure, education, and mechanisms to improve treatment adherence and persistence to optimize therapy.

Evolution of Resistance to Targeted Anti-Cancer Therapies during Continuous and Pulsed Administration Strategies

PubMed Central

Foo, Jasmine; Michor, Franziska

2009-01-01

The discovery of small molecules targeted to specific oncogenic pathways has revolutionized anti-cancer therapy. However, such therapy often fails due to the evolution of acquired resistance. One long-standing question in clinical cancer research is the identification of optimum therapeutic administration strategies so that the risk of resistance is minimized. In this paper, we investigate optimal drug dosing schedules to prevent, or at least delay, the emergence of resistance. We design and analyze a stochastic mathematical model describing the evolutionary dynamics of a tumor cell population during therapy. We consider drug resistance emerging due to a single (epi)genetic alteration and calculate the probability of resistance arising during specific dosing strategies. We then optimize treatment protocols such that the risk of resistance is minimal while considering drug toxicity and side effects as constraints. Our methodology can be used to identify optimum drug administration schedules to avoid resistance conferred by one (epi)genetic alteration for any cancer and treatment type. PMID:19893626

Optimizing management of actinic keratosis and photodamaged skin: utilizing a stepwise approach.

PubMed

Lee, Andrew D; Jorizzo, Joseph L

2009-09-01

The incidence of photodamaged skin and skin lesions of all degrees of severity, from actinic keratosis (AK) to skin cancers, has dramatically increased. Actinic keratoses are pathologic, reflecting damage of essential skin cell functions and potentially progressing to invasive squamous cell carcinoma (SCC). The rate of progression is uncertain but may be as high as 10%. Because it is impossible to predict which AKs will progress to SCC, all lesions should be treated. Options include topical therapies, cryotherapy, curettage, and photodynamic therapy. Unfortunately, many individuals do not seek treatment or avoid it because of irritation, discomfort, and concern for scarring. Combining field-directed therapy and cryotherapy has been more effective than cryotherapy alone. Incorporating patient education with treatment may optimize outcomes. We propose a comprehensive 5-step approach for managing AK lesions and photodamaged skin that includes periodic clinical skin examinations; treating AK lesions with a combination of field- and lesion-directed therapy; and patient education regarding sun-protective measures and regular skin self-examinations.

Driving personalized medicine: capturing maximum net present value and optimal return on investment.

PubMed

Roth, Mollie; Keeling, Peter; Smart, Dave

2010-01-01

In order for personalized medicine to meet its potential future promise, a closer focus on the work being carried out today and the foundation it will provide for that future is imperative. While big picture perspectives of this still nascent shift in the drug-development process are important, it is more important that today's work on the first wave of targeted therapies is used to build specific benchmarking and financial models against which further such therapies may be more effectively developed. Today's drug-development teams need a robust tool to identify the exact drivers that will ensure the successful launch and rapid adoption of targeted therapies, and financial metrics to determine the appropriate resource levels to power those drivers. This special report will describe one such benchmarking and financial model that is specifically designed for the personalized medicine field and will explain how the use of this or similar models can help to capture the maximum net present value of targeted therapies and help to realize optimal return on investment.

A randomized controlled trial testing an adherence-optimized Vitamin D regimen to mitigate bone change in adolescents being treated for acute lymphoblastic leukemia.

PubMed

Orgel, Etan; Mueske, Nicole M; Sposto, Richard; Gilsanz, Vicente; Wren, Tishya A L; Freyer, David R; Butturini, Anna M; Mittelman, Steven D

2017-10-01

Adolescents with acute lymphoblastic leukemia (ALL) develop osteopenia early in therapy, potentially exacerbated by high rates of concurrent Vitamin D deficiency. We conducted a randomized clinical trial testing a Vitamin D-based intervention to improve Vitamin D status and reduce bone density decline. Poor adherence to home supplementation necessitated a change to directly observed therapy (DOT) with intermittent, high-dose Vitamin D3 randomized versus standard of care (SOC). Compared to SOC, DOT Vitamin D3 successfully increased trough Vitamin 25(OH)D levels (p = .026) with no residual Vitamin D deficiency, 100% adherence to DOT Vitamin D3, and without associated toxicity. However, neither Vitamin D status nor supplementation impacted bone density. Thus, this adherence-optimized intervention is feasible and effective to correct Vitamin D deficiency in adolescents during ALL therapy. Repletion of Vitamin D and calcium alone did not mitigate osteopenia, however, and new, comprehensive approaches are needed to address treatment-associated osteopenia during ALL therapy.

Reduction of thermal damage in photodynamic therapy by laser irradiation techniques.

PubMed

Lim, Hyun Soo

2012-12-01

General application of continuous-wave (CW) laser irradiation modes in photodynamic therapy can cause thermal damage to normal tissues in addition to tumors. A new photodynamic laser therapy system using a pulse irradiation mode was optimized to reduce nonspecific thermal damage. In in vitro tissue specimens, tissue energy deposition rates were measured in three irradiation modes, CW, pulse, and burst-pulse. In addition, methods were tested for reducing variations in laser output and specific wavelength shifts using a thermoelectric cooler and thermistor. The average temperature elevation per 10 J/cm2 was 0.27°C, 0.09°C, and 0.08°C using the three methods, respectively, in pig muscle tissue. Variations in laser output were controlled within ± 0.2%, and specific wavelength shift was limited to ± 3 nm. Thus, optimization of a photodynamic laser system was achieved using a new pulse irradiation mode and controlled laser output to reduce potential thermal damage during conventional CW-based photodynamic therapy.

War, what is it good for? Historical contribution of the military and war to occupational therapy and hand therapy.

PubMed

Yakobina, Sheila Catherine; Yakobina, Stephanie Robin; Harrison-Weaver, Sandra

2008-01-01

War has negative connotations; nevertheless, this article aims to highlight some of the positive outcomes that have occurred in the fields of occupational therapy (OT) and hand therapy due to war and war-related injuries. From the military background of one of OT's founders, Thomas Kidner, to the valiant efforts of the reconstruction aides, to the origin of hand therapy during the Vietnam War, the military influence has been a powerful force in furthering our profession. This article reviews the unique history of war, the establishment and development of OT and hand therapy, and the contributions from military service members.

Guidelines for the Treatment of Hypothyroidism: Prepared by the American Thyroid Association Task Force on Thyroid Hormone Replacement

PubMed Central

Bianco, Antonio C.; Bauer, Andrew J.; Burman, Kenneth D.; Cappola, Anne R.; Celi, Francesco S.; Cooper, David S.; Kim, Brian W.; Peeters, Robin P.; Rosenthal, M. Sara; Sawka, Anna M.

2014-01-01

Background: A number of recent advances in our understanding of thyroid physiology may shed light on why some patients feel unwell while taking levothyroxine monotherapy. The purpose of this task force was to review the goals of levothyroxine therapy, the optimal prescription of conventional levothyroxine therapy, the sources of dissatisfaction with levothyroxine therapy, the evidence on treatment alternatives, and the relevant knowledge gaps. We wished to determine whether there are sufficient new data generated by well-designed studies to provide reason to pursue such therapies and change the current standard of care. This document is intended to inform clinical decision-making on thyroid hormone replacement therapy; it is not a replacement for individualized clinical judgment. Methods: Task force members identified 24 questions relevant to the treatment of hypothyroidism. The clinical literature relating to each question was then reviewed. Clinical reviews were supplemented, when relevant, with related mechanistic and bench research literature reviews, performed by our team of translational scientists. Ethics reviews were provided, when relevant, by a bioethicist. The responses to questions were formatted, when possible, in the form of a formal clinical recommendation statement. When responses were not suitable for a formal clinical recommendation, a summary response statement without a formal clinical recommendation was developed. For clinical recommendations, the supporting evidence was appraised, and the strength of each clinical recommendation was assessed, using the American College of Physicians system. The final document was organized so that each topic is introduced with a question, followed by a formal clinical recommendation. Stakeholder input was received at a national meeting, with some subsequent refinement of the clinical questions addressed in the document. Consensus was achieved for all recommendations by the task force. Results: We reviewed the following therapeutic categories: (i) levothyroxine therapy, (ii) non–levothyroxine-based thyroid hormone therapies, and (iii) use of thyroid hormone analogs. The second category included thyroid extracts, synthetic combination therapy, triiodothyronine therapy, and compounded thyroid hormones. Conclusions: We concluded that levothyroxine should remain the standard of care for treating hypothyroidism. We found no consistently strong evidence for the superiority of alternative preparations (e.g., levothyroxine–liothyronine combination therapy, or thyroid extract therapy, or others) over monotherapy with levothyroxine, in improving health outcomes. Some examples of future research needs include the development of superior biomarkers of euthyroidism to supplement thyrotropin measurements, mechanistic research on serum triiodothyronine levels (including effects of age and disease status, relationship with tissue concentrations, as well as potential therapeutic targeting), and long-term outcome clinical trials testing combination therapy or thyroid extracts (including subgroup effects). Additional research is also needed to develop thyroid hormone analogs with a favorable benefit to risk profile. PMID:25266247

Basic requirements and parameter optimization for boron neutron capture therapy of extracorporeal irradiated and auto-transplanted organs.

PubMed

Wortmann, Birgit; Knorr, Jürgen

2012-08-01

In 2001 and 2003, at the University of Pavia, Italy, boron neutron capture therapy (BNCT) has been successfully used in the treatment of hepatic colorectal metastases (Pinelli et al., 2002; Zonta et al., 2006). The treatment procedure (TAOrMINA protocol) is characterised by the auto-transplantation and extracorporeal irradiation of the liver using a thermal neutron beam. The clinical use of this approach requires well founded data and an optimized irradiation facility. In order to start with this work and to decide upon its feasibility at the research reactor TRIGA Mainz, basic data and requirements have been considered (Wortmann, 2008). Computer calculations using the ATTILA (Transpire Inc. 2006) and MCNP (LANL, 2005) codes have been performed, including data from conventional radiation therapy, from the TAOrMINA approach, resulting in reasonable estimations. Basic data and requirements and optimal parameters have been worked out, especially for use at an optimized TRIGA irradiation facility (Wortmann, 2008). Advantages of the extracorporeal irradiation with auto-transplantation and the potential of an optimized irradiation facility could be identified. Within the requirements, turning the explanted organ over by 180° appears preferable to a whole side source, similar to a permanent rotation of the organ. The design study and the parameter optimization confirm the potential of this approach to treat metastases in explanted organs. The results do not represent actual treatment data but a first estimation. Although all specific values refer to the TRIGA Mainz, they may act as a useful guide for other types of neutron sources. The recommended modifications (Wortmann, 2008) show the suitability of TRIGA reactors as a radiation source for BNCT of extracorporeal irradiated and auto-transplanted organs. Copyright © 2012 Elsevier Ltd. All rights reserved.

Beam angle optimization for intensity-modulated radiation therapy using a guided pattern search method

NASA Astrophysics Data System (ADS)

Rocha, Humberto; Dias, Joana M.; Ferreira, Brígida C.; Lopes, Maria C.

2013-05-01

Generally, the inverse planning of radiation therapy consists mainly of the fluence optimization. The beam angle optimization (BAO) in intensity-modulated radiation therapy (IMRT) consists of selecting appropriate radiation incidence directions and may influence the quality of the IMRT plans, both to enhance better organ sparing and to improve tumor coverage. However, in clinical practice, most of the time, beam directions continue to be manually selected by the treatment planner without objective and rigorous criteria. The goal of this paper is to introduce a novel approach that uses beam’s-eye-view dose ray tracing metrics within a pattern search method framework in the optimization of the highly non-convex BAO problem. Pattern search methods are derivative-free optimization methods that require a few function evaluations to progress and converge and have the ability to better avoid local entrapment. The pattern search method framework is composed of a search step and a poll step at each iteration. The poll step performs a local search in a mesh neighborhood and ensures the convergence to a local minimizer or stationary point. The search step provides the flexibility for a global search since it allows searches away from the neighborhood of the current iterate. Beam’s-eye-view dose metrics assign a score to each radiation beam direction and can be used within the pattern search framework furnishing a priori knowledge of the problem so that directions with larger dosimetric scores are tested first. A set of clinical cases of head-and-neck tumors treated at the Portuguese Institute of Oncology of Coimbra is used to discuss the potential of this approach in the optimization of the BAO problem.

[Lyme-Arthritis--a case report].

PubMed

von Ameln-Mayerhofer, Andreas

2016-05-01

Lyme disease is a serious infectious disease which, if untreated, does not recover and leads to further complications that might be severe. This exemplary case report describes a possible secondary Borrelia infection. It underlines that early antibiotic therapy in the correct dosage is essential. Furthermore, problems are discussed that might occur in context of the decision process concerning the best antibiotic substance and the optimal application route. Last but not least, possible problems associated with the discharge from hospital are discussed. In conclusion, early diagnosis together with an on-time optimal antibiotic therapy are fundamental in the clinical management of Lyme disease.

Impact of Matrix-Assisted Laser Desorption and Ionization Time-of-Flight and Antimicrobial Stewardship Intervention on Treatment of Bloodstream Infections in Hospitalized Children.

PubMed

Malcolmson, Caroline; Ng, Karen; Hughes, Shevaun; Kissoon, Niranjan; Schina, Jillian; Tilley, Peter A; Roberts, Ashley

2017-06-01

Early definitive identification of infectious pathogens coupled with antimicrobial stewardship interventions allow for targeted and timely administration of antimicrobials. We investigated the combined impact of matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) technology and an antimicrobial stewardship program (ASP) in pediatric patients with blood stream infections (BSIs). This is a single-center study comparing a control group of patients from October 2009 to July 2010 with BSIs to a cohort of patients postimplementation of MALDI-TOF and an ASP, from October 2013 to July 2014. Primary outcome was time to optimal therapy. Secondary outcomes included time to effective therapy, 30-day all-cause mortality, 30-day readmission rate, hospital length of stay, and intensive care admission. One hundred episodes of BSIs were identified in the preintervention period, and 121 episodes were identified in the postintervention period. Time from blood culture collection to organism identification was significantly reduced in the prospective cohort compared with historical controls (18.8 vs 43.7 hours, respectively). A total of 73 ASP interventions were made on the treatment of BSIs in the postintervention period. Combined use of MALDI-TOF and ASP significantly reduced time to optimal therapy (77.0 to 54.2 hours, P < .001). In the subgroup analysis of Gram-negative bacteremia, time to effective and optimal therapy were significantly reduced (2.0 vs 0.7 hours and 146.8 vs 48.0 hours, respectively). There were no significant differences in clinical outcomes. The combined use of MALDI-TOF and ASP allows early optimization of antimicrobial therapy in pediatric inpatients with BSIs. © The Author 2016. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Spot-Scanning Proton Arc (SPArc) Therapy: The First Robust and Delivery-Efficient Spot-Scanning Proton Arc Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ding, Xuanfeng, E-mail: Xuanfeng.ding@beaumont.org; Li, Xiaoqiang; Zhang, J. Michele

Purpose: To present a novel robust and delivery-efficient spot-scanning proton arc (SPArc) therapy technique. Methods and Materials: A SPArc optimization algorithm was developed that integrates control point resampling, energy layer redistribution, energy layer filtration, and energy layer resampling. The feasibility of such a technique was evaluated using sample patients: 1 patient with locally advanced head and neck oropharyngeal cancer with bilateral lymph node coverage, and 1 with a nonmobile lung cancer. Plan quality, robustness, and total estimated delivery time were compared with the robust optimized multifield step-and-shoot arc plan without SPArc optimization (Arc{sub multi-field}) and the standard robust optimized intensity modulatedmore » proton therapy (IMPT) plan. Dose-volume histograms of target and organs at risk were analyzed, taking into account the setup and range uncertainties. Total delivery time was calculated on the basis of a 360° gantry room with 1 revolutions per minute gantry rotation speed, 2-millisecond spot switching time, 1-nA beam current, 0.01 minimum spot monitor unit, and energy layer switching time of 0.5 to 4 seconds. Results: The SPArc plan showed potential dosimetric advantages for both clinical sample cases. Compared with IMPT, SPArc delivered 8% and 14% less integral dose for oropharyngeal and lung cancer cases, respectively. Furthermore, evaluating the lung cancer plan compared with IMPT, it was evident that the maximum skin dose, the mean lung dose, and the maximum dose to ribs were reduced by 60%, 15%, and 35%, respectively, whereas the conformity index was improved from 7.6 (IMPT) to 4.0 (SPArc). The total treatment delivery time for lung and oropharyngeal cancer patients was reduced by 55% to 60% and 56% to 67%, respectively, when compared with Arc{sub multi-field} plans. Conclusion: The SPArc plan is the first robust and delivery-efficient proton spot-scanning arc therapy technique, which could potentially be implemented into routine clinical practice.« less

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yamada, T; Fujii, Y; Hitachi Ltd., Hitachi-shi, Ibaraki

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-timemore » 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 Program.« less

The Treatment of Sexual Dysfunction in a University Health Service Setting

ERIC Educational Resources Information Center

Babineau, Raymond; Schwartz, Allan J.

1977-01-01

Experience of the authors indicates that solo therapists with adequate background in individual and couple therapy, who also have additional training/experience in sex therapy, can provide treatment for sexual dysfunction to student couples in a health service setting with encouraging results. (MB)

Personality Theory and Psychotherapy

ERIC Educational Resources Information Center

Fagan, Joen; And Others

1974-01-01

This group of articles discusses various aspects of Gestalt Therapy including its major contributions, role in psychotherapy, and contributions of Gestalt psychology in general. There is some discussion of the philosophical background of Gestalt therapy along with Gestalt theory of emotion. A case study and an annotated bibliography are included…

Active marks structure optimization for optical-electronic systems of spatial position control of industrial objects

NASA Astrophysics Data System (ADS)

Sycheva, Elena A.; Vasilev, Aleksandr S.; Lashmanov, Oleg U.; Korotaev, Valery V.

2017-06-01

The article is devoted to the optimization of optoelectronic systems of the spatial position of objects. Probabilistic characteristics of the detection of an active structured mark on a random noisy background are investigated. The developed computer model and the results of the study allow us to estimate the probabilistic characteristics of detection of a complex structured mark on a random gradient background, and estimate the error of spatial coordinates. The results of the study make it possible to improve the accuracy of measuring the coordinates of the object. Based on the research recommendations are given on the choice of parameters of the optimal mark structure for use in opticalelectronic systems for monitoring the spatial position of large-sized structures.

Prognostic benefit of optimum left ventricular lead position in cardiac resynchronization therapy: follow-up of the TARGET Study Cohort (Targeted Left Ventricular Lead Placement to guide Cardiac Resynchronization Therapy).

PubMed

Kydd, Anna C; Khan, Fakhar Z; Watson, William D; Pugh, Peter J; Virdee, Munmohan S; Dutka, David P

2014-06-01

This study was conducted to assess the impact of left ventricular (LV) lead position on longer-term survival after cardiac resynchronization therapy (CRT). An optimal LV lead position in CRT is associated with improved clinical outcome. A strategy of speckle-tracking echocardiography can be used to guide the implanter to the site of latest activation and away from segments of low strain amplitude (scar). Long-term, prospective survival data according to LV lead position in CRT are limited. Data from a follow-up registry of 250 consecutive patients receiving CRT between June 2008 and July 2010 were studied. The study population comprised patients recruited to the derivation group and the subsequent TARGET (Targeted Left Ventricular Lead Placement to guide Cardiac Resynchronization Therapy) randomized, controlled trial. Final LV lead position was described, in relation to the pacing site determined by pre-procedure speckle-tracking echocardiography, as optimal (concordant/adjacent) or suboptimal (remote). All-cause mortality was recorded at follow-up. An optimal LV lead position (n = 202) conferred LV remodeling response superior to that of a suboptimal lead position (change in LV end-systolic volume: -24 ± 15% vs. -12 ± 17% [p < 0.001]; change in ejection fraction: +7 ± 8% vs. +4 ± 7% [p = 0.02]). During long-term follow-up (median: 39 months; range: <1 to 61 months), an optimal LV lead position was associated with improved survival (log-rank p = 0.003). A suboptimal LV lead placement independently predicted all-cause mortality (hazard ratio: 1.8; p = 0.024). An optimal LV lead position at the site of latest mechanical activation, avoiding low strain amplitude (scar), was associated with superior CRT response and improved survival that persisted during follow-up. Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Long-term pain relief with optimized medical treatment including antioxidants and step-up interventional therapy in patients with chronic pancreatitis.

PubMed

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.

Impact of Reflex EGFR/ ALK Testing on Time to Treatment of Patients With Advanced Nonsquamous Non-Small-Cell Lung Cancer.

PubMed

Cheema, Parneet K; Menjak, Ines B; Winterton-Perks, Zoe; Raphael, Simon; Cheng, Susanna Y; Verma, Sunil; Muinuddin, Ahmad; Freedman, Ryan; Toor, Nevkeet; Perera, Joseph; Anaka, Matthew; Victor, J Charles

2017-02-01

Optimal first-line systemic therapy for patients with advanced nonsquamous (nonsq) non-small-cell lung cancer (NSCLC) requires confirmation of EGFR/ ALK status, which can delay treatment. We evaluated the impact of reflex testing, defined as pathologists initiating EGFR/ ALK testing at the time of diagnosis of nonsq NSCLC, on time to treatment (TTT). We conducted a retrospective review of patients with nonsq NSCLC with medical oncology consultation at Sunnybrook Odette Cancer Centre between March 18, 2010 and April 30, 2014. Data were compared during routine and reflex testing. TTT was defined as the interval between the first medical oncology visit with advanced NSCLC and the initiation of systemic therapy. A total of 306 patients were included (n = 232 for routine testing, n = 74 for reflex testing). There was a trend to improvement in median TTT with reflex testing (36 days [interquartile range {IQR}, 16 to 71 days v 26 days [IQR, 8 to 41 days], P = .071). Omitting patients with intentional delays in systemic therapy for low-volume disease, poor performance status, comorbidity management, and/or radiation therapy, median TTT improved (34 days [IQR, 15 to 67 days] v 22 days [IQR, 8 to 42 days], P = .049). Time to optimal first-line systemic therapy according to published guidelines improved (median, 36 days [IQR, 16 to 91 days] v 24 days [IQR, 8 to 43 days], P = .036). There was no impact on receipt of any first-line systemic therapy (55% v 59%, P = .66). The quality of biomarker testing improved, with fewer unsuccessful tests ( EGFR, 14% v 4%, P = .039; and ALK, 17% v 3%, P = .037). Reflex testing of EGFR/ ALK improved the time to optimal systemic therapy and the quality of biomarker testing for patients with advanced nonsq NSCLC.

Should psychology be ‘positive’? Letting the philosophers speak

PubMed Central

Oyebode, Femi

2014-01-01

This is a brief commentary on the value of optimism in therapy. It draws on the philosophical writings of Schopenhauer and Aristotle. It suggests that the modern preoccupation with optimism may be as extreme as the bleak pessimistic outlook favoured by Schopenhauer. PMID:25237498

Switches in Genomic GC Content Drive Shifts of Optimal Codons under Sustained Selection on Synonymous Sites

PubMed Central

Sun, Yu; Tamarit, Daniel

2017-01-01

Abstract The major codon preference model suggests that codons read by tRNAs in high concentrations are preferentially utilized in highly expressed genes. However, the identity of the optimal codons differs between species although the forces driving such changes are poorly understood. We suggest that these questions can be tackled by placing codon usage studies in a phylogenetic framework and that bacterial genomes with extreme nucleotide composition biases provide informative model systems. Switches in the background substitution biases from GC to AT have occurred in Gardnerella vaginalis (GC = 32%), and from AT to GC in Lactobacillus delbrueckii (GC = 62%) and Lactobacillus fermentum (GC = 63%). We show that despite the large effects on codon usage patterns by these switches, all three species evolve under selection on synonymous sites. In G. vaginalis, the dramatic codon frequency changes coincide with shifts of optimal codons. In contrast, the optimal codons have not shifted in the two Lactobacillus genomes despite an increased fraction of GC-ending codons. We suggest that all three species are in different phases of an on-going shift of optimal codons, and attribute the difference to a stronger background substitution bias and/or longer time since the switch in G. vaginalis. We show that comparative and correlative methods for optimal codon identification yield conflicting results for genomes in flux and discuss possible reasons for the mispredictions. We conclude that switches in the direction of the background substitution biases can drive major shifts in codon preference patterns even under sustained selection on synonymous codon sites. PMID:27540085

Interaction between Vestibular Compensation Mechanisms and Vestibular Rehabilitation Therapy: 10 Recommendations for Optimal Functional Recovery

PubMed Central

Lacour, Michel; Bernard-Demanze, Laurence

2015-01-01

This review questions the relationships between the plastic events responsible for the recovery of vestibular function after a unilateral vestibular loss (vestibular compensation), which has been well described in animal models in the last decades, and the vestibular rehabilitation (VR) therapy elaborated on a more empirical basis for vestibular loss patients. The main objective is not to propose a catalog of results but to provide clinicians with an understandable view on when and how to perform VR therapy, and why VR may benefit from basic knowledge and may influence the recovery process. With this perspective, 10 major recommendations are proposed as ways to identify an optimal functional recovery. Among them are the crucial role of active and early VR therapy, coincidental with a post-lesion sensitive period for neuronal network remodeling, the instructive role that VR therapy may play in this functional reorganization, the need for progression in the VR therapy protocol, which is based mainly on adaptation processes, the necessity to take into account the sensorimotor, cognitive, and emotional profile of the patient to propose individual or “à la carte” VR therapies, and the importance of motivational and ecologic contexts. More than 10 general principles are very likely, but these principles seem crucial for the fast recovery of vestibular loss patients to ensure good quality of life. PMID:25610424

Cost-Effectiveness of Nivolumab-Ipilimumab Combination Therapy Compared to Monotherapy for First-Line Treatment of Metastatic Melanoma in the United States

PubMed Central

Oh, Anna; Tran, Dang M; McDowell, Leann C; Keyvani, Dor; Barcelon, Jay Andrew; Merino, Oscar; Wilson, Leslie

2018-01-01

BACKGROUND The approval of new immunotherapies has dramatically changed the treatment landscape of metastatic melanoma. These survival gains come with trade-offs in side effects and costs, as well as important considerations to third-party payer systems, physicians, and patients. OBJECTIVE Develop a Markov model to determine the cost-effectiveness of nivolumab, ipilimumab, and nivolumab-ipilimumab combination as first-line therapy in metastatic melanoma while accounting for differential effectiveness in PD-L1 positive and negative patients. METHODS A three-state Markov model (‘PD-L1 positive stable disease’, ‘PD-L1 negative stable disease’, and ‘Progression and/or Death’) was developed using a US societal perspective with a lifetime time horizon of 14.5 years. Transition probabilities were calculated from progression-free survival data reported in the CheckMate-067 trial. Costs were expressed in 2015 US dollars and were determined using national sources. Adverse event (AE) management was determined using immune-related AE (irAE) data from CheckMate-067, irAE management guides for nivolumab and ipilimumab, and treatment guidelines. Utilities were obtained from published literature, using melanoma-specific studies when available, and were weighted based on incidence and duration of irAEs. Base case, one-way sensitivity, and probabilistic sensitivity analyses were conducted. RESULTS Nivolumab-ipilimumab combination therapy is not the cost effective choice ($454,092 per progression-free quality-adjusted-life-year [PFQALY]) compared to nivolumab monotherapy in our base case analysis at a willingness-to-pay threshold of $100,000/PFQALY. Both combination therapy and nivolumab monotherapy were cost-effective choices compared to ipilimumab monotherapy. PD-L1 positive status, utility of nivolumab and combination therapy, and medication costs contributed the most uncertainty to the model. In a population of 100% PD-L1 negative patients, nivolumab was still the optimal treatment but combination therapy had an improved ICER of $295,903/PFQALY. Combination therapy became dominated by nivolumab when 68% of the sample was PD-L1 positive. In addition, the cost of ipilimumab would have to decrease to <$21,555 per dose for combination therapy to have an ICER <$100,000/PFQALY, and to <$19,151 (a 42% reduction) to be more cost-effective than nivolumab monotherapy. CONCLUSIONS Nivolumab-ipilimumab combination therapy is not cost-effective compared to nivolumab monotherapy, which is the most cost-effective option. Professionals in managed care settings should consider the pharmacoeconomic implications of these new immunotherapies as they make value-based formulary decisions and future cost-effectiveness studies are completed. PMID:28530525

[Adequate anti-infective treatment : Importance of individual dosing and application].

PubMed

Brinkmann, A; Röhr, A C; Köberer, A; Fuchs, T; Krüger, W A; König, C; Richter, D; Weigand, M A; Frey, O R

2018-05-15

Sepsis-induced changes in pharmacokinetic parameters are a well-known problem in intensive care medicine. Dosing of antibiotics in this setting is therefore challenging. Alterations to the substance-specific kinetics of anti-infective substances have an effect on the distribution and excretion processes in the body. Increased clearance and an increased distribution volume (V d ) and particularly compromized organ function with reduced antibiotic elimination are often encountered in patients with sepsis. Renal replacement treatment, which is frequently used in intensive care medicine, represents a substantial intervention in this system. Current international guidelines recommend individualized dosing strategies and adaptation of doses according to measured serum levels and pharmacokinetic/pharmacodynamic (PK/PD) parameters as concepts to optimize anti-infective therapy in the critically ill. Likewise, the recommendation to adjust the administration form of beat-lactam antibiotics to prolonged or continuous infusion can be found increasingly more often in the literature. This article reviews the background of the individual dosing in intensive care patients and their applicability to the clinical routine.

Modeling Patient-Specific Magnetic Drug Targeting Within the Intracranial Vasculature

PubMed Central

Patronis, Alexander; Richardson, Robin A.; Schmieschek, Sebastian; Wylie, Brian J. N.; Nash, Rupert W.; Coveney, Peter V.

2018-01-01

Drug targeting promises to substantially enhance future therapies, for example through the focussing of chemotherapeutic drugs at the site of a tumor, thus reducing the exposure of healthy tissue to unwanted damage. Promising work on the steering of medication in the human body employs magnetic fields acting on nanoparticles made of paramagnetic materials. We develop a computational tool to aid in the optimization of the physical parameters of these particles and the magnetic configuration, estimating the fraction of particles reaching a given target site in a large patient-specific vascular system for different physiological states (heart rate, cardiac output, etc.). We demonstrate the excellent computational performance of our model by its application to the simulation of paramagnetic-nanoparticle-laden flows in a circle of Willis geometry obtained from an MRI scan. The results suggest a strong dependence of the particle density at the target site on the strength of the magnetic forcing and the velocity of the background fluid flow. PMID:29725303

Modeling Patient-Specific Magnetic Drug Targeting Within the Intracranial Vasculature.

PubMed

Patronis, Alexander; Richardson, Robin A; Schmieschek, Sebastian; Wylie, Brian J N; Nash, Rupert W; Coveney, Peter V

2018-01-01

Drug targeting promises to substantially enhance future therapies, for example through the focussing of chemotherapeutic drugs at the site of a tumor, thus reducing the exposure of healthy tissue to unwanted damage. Promising work on the steering of medication in the human body employs magnetic fields acting on nanoparticles made of paramagnetic materials. We develop a computational tool to aid in the optimization of the physical parameters of these particles and the magnetic configuration, estimating the fraction of particles reaching a given target site in a large patient-specific vascular system for different physiological states (heart rate, cardiac output, etc.). We demonstrate the excellent computational performance of our model by its application to the simulation of paramagnetic-nanoparticle-laden flows in a circle of Willis geometry obtained from an MRI scan. The results suggest a strong dependence of the particle density at the target site on the strength of the magnetic forcing and the velocity of the background fluid flow.

Report of a workshop on research gaps in the treatment of cerebral palsy

PubMed Central

Hirtz, Deborah; Damiano, Diane; Gross, Paul; Mink, Jonathan W.

2016-01-01

Cerebral palsy (CP) is heterogeneous in etiology and manifestations, making research into relevant therapies difficult and limiting the generalizability of the results. We report here on the NIH CP symposium, where stakeholders from academic, clinical, regulatory, and advocacy backgrounds discussed the major challenges and needs for moving forward with clinical research in CP, and outlined priorities and action items. New information is constantly generated through research into pathogenesis and etiology. Clinical research and new therapeutic approaches need to keep pace, through large data registry integration and new research designs. Development of standardized data collection, increasing academic focus on CP research, and iterative approaches to treatment throughout the patients' lives, have all been identified as areas of focus. The workshop identified critical gaps and areas of focus to increase the evidence base for therapeutic approaches to determine which treatments work best for which patients in the near future. These include consolidation and optimization of databases and registries, updates to the research methodology, and better integration of resources and stakeholders. PMID:27558377

Macrolide Therapy in Adults and Children with Non-Cystic Fibrosis Bronchiectasis: A Systematic Review and Meta-Analysis

PubMed Central

Tang, Yan; Gao, Yang; Lin, Zhi-ya; Lin, Zhi-min; Zhong, Nan-shan; Chen, Rong-chang

2014-01-01

Background A systematic review and meta-analysis was conducted to evaluate the efficacy and safety of macrolide therapy in adults and children with bronchiectasis. Methods We searched the PUBMED, EMBASE, CENTRAL databases to identify relevant studies. Two reviewers evaluated the studies and extracted data independently. The primary outcome was the number of bronchiectasis exacerbations. Secondary outcomes included exacerbation-related admissions, quality of life (QoL), spirometry, 6-minute walk test (6MWT) and adverse events. Results Nine eligible trials with 559 participants were included. Six were conducted on adults, and the remaining on children. Macrolide therapy significantly reduced the number of patients experiencing one or more exacerbation in adults [risk ratio (RR) = 0.59; 95% CI, 0.40 to 0.86; P = 0.006; I2 = 65%] and children [RR = 0.86; 95% CI, 0.75–0.99; P = 0.04; I2 = 0%], but not the number of patients with admissions for exacerbation. Macrolide therapy was also associated with reduced frequency of exacerbations in adults (RR = 0.42; 95% CI, 0.29 to 0.61; P<0.001; I2 = 64%) and children (RR = 0.50; 95% CI, 0.35 to 0.71; P<0.001). Pooled analyses suggested that spirometry, including FEV1 and FVC, were significantly improved in adults but not in children. Macrolide therapy improved the QoL (WMD, −6.56; 95% CI, −11.99 to −1.12; P = 0.02; I2 = 86%) but no significant difference in 6MWT (WMD, 4.15; 95% CI, −11.83 to 20.13; P = 0.61; I2 = 31%) and the overall adverse events (RR, 0.96; 95% CI, 0.82 to 1.13; P = 0.66; I2 = 0%) in adults. However, reports of diarrhea and abdominal discomforts were higher with macrolide therapy. Conclusions Macrolide maintenance therapy, both in adults and children, was effective and safe in reducing bronchiectasis exacerbations, but not the admissions for exacerbations. In addition, macrolide administration in adults was associated with improvement in QoL and spirometry, but not 6WMT. Future studies are warranted to verify the optimal populations and clarify its potential effects on antimicrobial resistance. PMID:24603554

Optimal mapping of neural-network learning on message-passing multicomputers

NASA Technical Reports Server (NTRS)

Chu, Lon-Chan; Wah, Benjamin W.

1992-01-01

A minimization of learning-algorithm completion time is sought in the present optimal-mapping study of the learning process in multilayer feed-forward artificial neural networks (ANNs) for message-passing multicomputers. A novel approximation algorithm for mappings of this kind is derived from observations of the dominance of a parallel ANN algorithm over its communication time. Attention is given to both static and dynamic mapping schemes for systems with static and dynamic background workloads, as well as to experimental results obtained for simulated mappings on multicomputers with dynamic background workloads.

Preoperative therapy in locally advanced esophageal cancer.

PubMed

Garg, Pankaj Kumar; Sharma, Jyoti; Jakhetiya, Ashish; Goel, Aakanksha; Gaur, Manish Kumar

2016-10-21

Esophageal cancer is an aggressive malignancy associated with dismal treatment outcomes. Presence of two distinct histopathological types distinguishes it from other gastrointestinal tract malignancies. Surgery is the cornerstone of treatment in locally advanced esophageal cancer (T2 or greater or node positive); however, a high rate of disease recurrence (systemic and loco-regional) and poor survival justifies a continued search for optimal therapy. Various combinations of multimodality treatment (preoperative/perioperative, or postoperative; radiotherapy, chemotherapy, or chemoradiotherapy) are being explored to lower disease recurrence and improve survival. Preoperative therapy followed by surgery is presently considered the standard of care in resectable locally advanced esophageal cancer as postoperative treatment may not be feasible for all the patients due to the morbidity of esophagectomy and prolonged recovery time limiting the tolerance of patient. There are wide variations in the preoperative therapy practiced across the centres depending upon the institutional practices, availability of facilities and personal experiences. There is paucity of literature to standardize the preoperative therapy. Broadly, chemoradiotherapy is the preferred neo-adjuvant modality in western countries whereas chemotherapy alone is considered optimal in the far East. The present review highlights the significant studies to assist in opting for the best evidence based preoperative therapy (radiotherapy, chemotherapy or chemoradiotherapy) for locally advanced esophageal cancer.

Task-based image quality assessment in radiation therapy: initial characterization and demonstration with CT simulation images

NASA Astrophysics Data System (ADS)

Dolly, Steven R.; Anastasio, Mark A.; Yu, Lifeng; Li, Hua

2017-03-01

In current radiation therapy practice, image quality is still assessed subjectively or by utilizing physically-based metrics. Recently, a methodology for objective task-based image quality (IQ) assessment in radiation therapy was proposed by Barrett et al.1 In this work, we present a comprehensive implementation and evaluation of this new IQ assessment methodology. A modular simulation framework was designed to perform an automated, computer-simulated end-to-end radiation therapy treatment. A fully simulated framework was created that utilizes new learning-based stochastic object models (SOM) to obtain known organ boundaries, generates a set of images directly from the numerical phantoms created with the SOM, and automates the image segmentation and treatment planning steps of a radiation therapy work ow. By use of this computational framework, therapeutic operating characteristic (TOC) curves can be computed and the area under the TOC curve (AUTOC) can be employed as a figure-of-merit to guide optimization of different components of the treatment planning process. The developed computational framework is employed to optimize X-ray CT pre-treatment imaging. We demonstrate that use of the radiation therapy-based-based IQ measures lead to different imaging parameters than obtained by use of physical-based measures.

Risk assessment and comparative effectiveness of left ventricular assist device and medical management in ambulatory heart failure patients: design and rationale of the ROADMAP clinical trial.

PubMed

Rogers, Joseph G; Boyle, Andrew J; O'Connell, John B; Horstmanshof, Douglas A; Haas, Donald C; Slaughter, Mark S; Park, Soon J; Farrar, David J; Starling, Randall C

2015-02-01

Mechanical circulatory support is now a proven therapy for the treatment of patients with advanced heart failure and cardiogenic shock. The role for this therapy in patients with less severe heart failure is unknown. The objective of this study is to examine the impact of mechanically assisted circulation using the HeartMate II left ventricular assist device in patients who meet current US Food and Drug Administration-defined criteria for treatment but are not yet receiving intravenous inotropic therapy. This is a prospective, nonrandomized clinical trial of 200 patients treated with either optimal medical management or a mechanical circulatory support device. This trial will be the first prospective clinical evaluation comparing outcomes of patients with advanced ambulatory heart failure treated with either ongoing medical therapy or a left ventricular assist device. It is anticipated to provide novel insights regarding relative outcomes with each treatment and an understanding of patient and provider acceptance of the ventricular assist device therapy. This trial will also provide information regarding the risk of events in "stable" patients with advanced heart failure and guidance for the optimal timing of left ventricular assist device therapy. Copyright © 2014 Elsevier Inc. All rights reserved.

Modeling antibiotic treatment in hospitals: A systematic approach shows benefits of combination therapy over cycling, mixing, and mono-drug therapies.

PubMed

Tepekule, Burcu; Uecker, Hildegard; Derungs, Isabel; Frenoy, Antoine; Bonhoeffer, Sebastian

2017-09-01

Multiple treatment strategies are available for empiric antibiotic therapy in hospitals, but neither clinical studies nor theoretical investigations have yielded a clear picture when which strategy is optimal and why. Extending earlier work of others and us, we present a mathematical model capturing treatment strategies using two drugs, i.e the multi-drug therapies referred to as cycling, mixing, and combination therapy, as well as monotherapy with either drug. We randomly sample a large parameter space to determine the conditions determining success or failure of these strategies. We find that combination therapy tends to outperform the other treatment strategies. By using linear discriminant analysis and particle swarm optimization, we find that the most important parameters determining success or failure of combination therapy relative to the other treatment strategies are the de novo rate of emergence of double resistance in patients infected with sensitive bacteria and the fitness costs associated with double resistance. The rate at which double resistance is imported into the hospital via patients admitted from the outside community has little influence, as all treatment strategies are affected equally. The parameter sets for which combination therapy fails tend to fall into areas with low biological plausibility as they are characterised by very high rates of de novo emergence of resistance to both drugs compared to a single drug, and the cost of double resistance is considerably smaller than the sum of the costs of single resistance.

[Antibiotics in the critically ill].

PubMed

Kolak, Radmila R

2010-01-01

Antibiotics are one the most common therapies administered in the intensive care unit setting. This review outlines the strategy for optimal use of antimicrobial agents in the critically ill. In severely ill patients, empirical antimicrobial therapy should be used when a suspected infection may impair the outcome. It is necessary to collect microbiological documentation before initiating empirical antimicrobial therapy. In addition to antimicrobial therapy, it is recommended to control a focus of infection and to modify factors that promote microbial growth or impair the host's antimicrobial defence. A judicious choice of antimicrobial therapy should be based on the host characteristics, the site of injection, the local ecology, and the pharmacokinetics/pharmacodynamics of antibiotics. This means treating empirically with broad-spectrum antimicrobials as soon as possible and narrowing the spectrum once the organism is identified (de-escalation), and limiting duration of therapy to the minimum effective period. Despite theoretical advantages, a combined antibiotic therapy is nor more effective than a mono-therapy in curing infections in most clinical trials involving intensive care patients. Nevertheless, textbooks and guidelines recommend a combination for specific pathogens and for infections commonly caused by these pathogens. Avoiding unnecessary antibiotic use and optimizing the administration of antimicrobial agents will improve patient outcomes while minimizing risks for the development of bacterial resistance. It is important to note that each intensive care unit should have a program in place which monitors antibiotic utilisation and its effectiveness. Only in this way can the impact of interventions aimed at improving antibiotic use be evaluated at the local level.

Electroconvulsive Therapy Intervention for Parkinson's Disease.

PubMed

Narang, Puneet; Glowacki, Anna; Lippmann, Steven

2015-01-01

Electroconvulsive therapy is an established means to improve function in a variety of psychiatric and neurologic conditions, particularly for patients who remain treatment-refractory. Parkinson's disease is a neurodegenerative disorder that sometimes does not respond well to conventional pharmacotherapies. Reports have indicated that electroconvulsive therapy may be an effective and safe treatment for those patients with Parkinson's disease who are not optimally responding to first-line treatments. Despite these reports, however, electroconvulsive therapy is not often used by clinicians in patients with treatment-resistant Parkinson's disease, perhaps due to stigma, lack of knowledge regarding its safety and efficacy, and/or inability to predict the duration of therapeutic benefit. Our objective was to determine if the available literature on ECT supports it as a safe and effective treatment option in patients with treatment-refractory Parkinson's disease. Motoric improvement induced by electroconvulsive therapy has been documented for decades in persons with Parkinson's disease. Efficacy and safety are reported following electroconvulsive therapy in people with Parkinson's disease who have sub-optimal response to medicines or experience the "on/off" phenomenon to L-dopa. Electroconvulsive therapy is an effective option for acute and maintenance treatment of Parkinson's disease in select patients. Inability to predict how long the beneficial effects of ECT therapy will last in patients with Parkinson's disease may be a reason why this treatment is underutilized by clinicians. More research is warranted to clarify parameters for application and duration of therapeutic benefit in individuals with difficult-to-treat Parkinson's disease.

Current and future management of treatment failure in low- and middle-income countries.

PubMed

Boyd, Mark A

2010-01-01

Access to second-line therapy in low- and middle-income countries has been limited to date. The WHO predicts that between 500 000 and 800 000 HIV-infected people on first-line combination antiretroviral therapy will require switch to second-line therapy by 2010. This paper aims to describe and review access to second-line therapy in low- and middle-income countries at present and examine future possibilities. The majority of HIV-infected patients failing first-line combination antiretroviral therapy is identified by way of routine monitoring of clinical and immunological status as a surrogate for virological monitoring. Evidence suggests that immunological and clinical monitoring lack both sensitivity and specificity for virological failure. Consequently, at treatment failure, patients have often selected a degree of resistance within the nucleoside/nucleotide reverse transcriptase inhibitor class that questions the efficacy of using nucleoside/nucleotide reverse transcriptase inhibitors in a second-line regimen. There is a paucity of good-quality evidence on which to base guidelines and policy. Optimally, a second-line regimen would be simple, potent, tolerable and lend itself to provision according to the successful 'public health' approach. Provision of second-line therapy to HIV-infected individuals failing first-line therapy is a major challenge to the ongoing success of access to HIV care programmes in low- and middle-income countries. The optimal second-line combination antiretroviral therapies are unknown. Research trials to help define best practice are in advanced stages of development and implementation.

Breast Cancer-Related Arm Lymphedema: Incidence Rates, Diagnostic Techniques, Optimal Management and Risk Reduction Strategies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shah, Chirag; Vicini, Frank A., E-mail: fvicini@beaumont.edu

As more women survive breast cancer, long-term toxicities affecting their quality of life, such as lymphedema (LE) of the arm, gain importance. Although numerous studies have attempted to determine incidence rates, identify optimal diagnostic tests, enumerate efficacious treatment strategies and outline risk reduction guidelines for breast cancer-related lymphedema (BCRL), few groups have consistently agreed on any of these issues. As a result, standardized recommendations are still lacking. This review will summarize the latest data addressing all of these concerns in order to provide patients and health care providers with optimal, contemporary recommendations. Published incidence rates for BCRL vary substantially withmore » a range of 2-65% based on surgical technique, axillary sampling method, radiation therapy fields treated, and the use of chemotherapy. Newer clinical assessment tools can potentially identify BCRL in patients with subclinical disease with prospective data suggesting that early diagnosis and management with noninvasive therapy can lead to excellent outcomes. Multiple therapies exist with treatments defined by the severity of BCRL present. Currently, the standard of care for BCRL in patients with significant LE is complex decongestive physiotherapy (CDP). Contemporary data also suggest that a multidisciplinary approach to the management of BCRL should begin prior to definitive treatment for breast cancer employing patient-specific surgical, radiation therapy, and chemotherapy paradigms that limit risks. Further, prospective clinical assessments before and after treatment should be employed to diagnose subclinical disease. In those patients who require aggressive locoregional management, prophylactic therapies and the use of CDP can help reduce the long-term sequelae of BCRL.« less

Design of optimal hyperthermia protocols for prostate cancer by controlling HSP expression through computer modeling (Invited Paper)

NASA Astrophysics Data System (ADS)

Rylander, Marissa N.; Feng, Yusheng; Diller, Kenneth; Bass, J.

2005-04-01

Heat shock proteins (HSP) are critical components of a complex defense mechanism essential for preserving cell survival under adverse environmental conditions. It is inevitable that hyperthermia will enhance tumor tissue viability, due to HSP expression in regions where temperatures are insufficient to coagulate proteins, and would likely increase the probability of cancer recurrence. Although hyperthermia therapy is commonly used in conjunction with radiotherapy, chemotherapy, and gene therapy to increase therapeutic effectiveness, the efficacy of these therapies can be substantially hindered due to HSP expression when hyperthermia is applied prior to these procedures. Therefore, in planning hyperthermia protocols, prediction of the HSP response of the tumor must be incorporated into the treatment plan to optimize the thermal dose delivery and permit prediction of overall tissue response. In this paper, we present a highly accurate, adaptive, finite element tumor model capable of predicting the HSP expression distribution and tissue damage region based on measured cellular data when hyperthermia protocols are specified. Cubic spline representations of HSP27 and HSP70, and Arrhenius damage models were integrated into the finite element model to enable prediction of the HSP expression and damage distribution in the tissue following laser heating. Application of the model can enable optimized treatment planning by controlling of the tissue response to therapy based on accurate prediction of the HSP expression and cell damage distribution.

4D Optimization of Scanned Ion Beam Tracking Therapy for Moving Tumors

PubMed Central

Eley, John Gordon; Newhauser, Wayne David; Lüchtenborg, Robert; Graeff, Christian; Bert, Christoph

2014-01-01

Motion mitigation strategies are needed to fully realize the theoretical advantages of scanned ion beam therapy for patients with moving tumors. The purpose of this study was to determine whether a new four-dimensional (4D) optimization approach for scanned-ion-beam tracking could reduce dose to avoidance volumes near a moving target while maintaining target dose coverage, compared to an existing 3D-optimized beam tracking approach. We tested these approaches computationally using a simple 4D geometrical phantom and a complex anatomic phantom, that is, a 4D computed tomogram of the thorax of a lung cancer patient. We also validated our findings using measurements of carbon-ion beams with a motorized film phantom. Relative to 3D-optimized beam tracking, 4D-optimized beam tracking reduced the maximum predicted dose to avoidance volumes by 53% in the simple phantom and by 13% in the thorax phantom. 4D-optimized beam tracking provided similar target dose homogeneity in the simple phantom (standard deviation of target dose was 0.4% versus 0.3%) and dramatically superior homogeneity in the thorax phantom (D5-D95 was 1.9% versus 38.7%). Measurements demonstrated that delivery of 4D-optimized beam tracking was technically feasible and confirmed a 42% decrease in maximum film exposure in the avoidance region compared with 3D-optimized beam tracking. In conclusion, we found that 4D-optimized beam tracking can reduce the maximum dose to avoidance volumes near a moving target while maintaining target dose coverage, compared with 3D-optimized beam tracking. PMID:24889215

4D optimization of scanned ion beam tracking therapy for moving tumors

NASA Astrophysics Data System (ADS)

Eley, John Gordon; Newhauser, Wayne David; Lüchtenborg, Robert; Graeff, Christian; Bert, Christoph

2014-07-01

Motion mitigation strategies are needed to fully realize the theoretical advantages of scanned ion beam therapy for patients with moving tumors. The purpose of this study was to determine whether a new four-dimensional (4D) optimization approach for scanned-ion-beam tracking could reduce dose to avoidance volumes near a moving target while maintaining target dose coverage, compared to an existing 3D-optimized beam tracking approach. We tested these approaches computationally using a simple 4D geometrical phantom and a complex anatomic phantom, that is, a 4D computed tomogram of the thorax of a lung cancer patient. We also validated our findings using measurements of carbon-ion beams with a motorized film phantom. Relative to 3D-optimized beam tracking, 4D-optimized beam tracking reduced the maximum predicted dose to avoidance volumes by 53% in the simple phantom and by 13% in the thorax phantom. 4D-optimized beam tracking provided similar target dose homogeneity in the simple phantom (standard deviation of target dose was 0.4% versus 0.3%) and dramatically superior homogeneity in the thorax phantom (D5-D95 was 1.9% versus 38.7%). Measurements demonstrated that delivery of 4D-optimized beam tracking was technically feasible and confirmed a 42% decrease in maximum film exposure in the avoidance region compared with 3D-optimized beam tracking. In conclusion, we found that 4D-optimized beam tracking can reduce the maximum dose to avoidance volumes near a moving target while maintaining target dose coverage, compared with 3D-optimized beam tracking.

High dose simvastatin exhibits enhanced lipid lowering effects relative to simvastatin/ezetimibe combination therapy

USDA-ARS?s Scientific Manuscript database

Technical Abstract: Background: Statins are the frontline in cholesterol reduction therapies; however use in combination with agents that possess complimentary mechanisms of action may achieve further reduce in LDL-C. Methods and Results: Thirty-nine patients were treated with either 80mg simvasta...

Children with Speech and Language Disability: Caseload Characteristics

ERIC Educational Resources Information Center

Broomfield, Jan; Dodd, Barbara

2004-01-01

Background: There has been no previous incidence survey of children referred to a speech and language therapy service in the UK. Previous studies of prevalence of specific communication difficulties provide contradictory data from which it is difficult to plan speech and language therapy service provision. Reliable data are needed concerning the…

77 FR 45061 - Hospital Outpatient Prospective and Ambulatory Surgical Center Payment Systems and Quality...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-30

... radiation therapy (IORT), brachytherapy composite APC, multiple imaging composite APCs, cardiac... Outpatient Code Editor IOL Intraocular lens IOM Institute of Medicine IORT Intraoperative radiation treatment... Radiation Therapy (IORT) (APC 0412) a. Background b. CY 2013 Proposals for CPT Codes 77424, 77425, and 77469...

Effectiveness of Speech Therapy in Adults with Intellectual Disabilities

ERIC Educational Resources Information Center

Terband, Hayo; Coppens-Hofman, Marjolein C.; Reffeltrath, Maaike; Maassen, Ben A. M.

2018-01-01

Background: This study investigated the effect of speech therapy in a heterogeneous group of adults with intellectual disability. Method: Thirty-six adults with mild and moderate intellectual disabilities (IQs 40-70; age 18-40 years) with reported poor speech intelligibility received tailored training in articulation and listening skills delivered…

Intrathecal Baclofen Therapy: Benefits and Complications

ERIC Educational Resources Information Center

Zdolsek, Helena Aniansson; Olesch, Christine; Antolovich, Giuliana; Reddihough, Dinah

2011-01-01

Background: Spasticity and dystonia in children with cerebral palsy has been treated with intrathecal baclofen therapy (ITB) at the Royal Children's Hospital, Melbourne, Australia (RCH) since 1999. Methods: The records of children having received or still receiving ITB during the period September 1999 until August 2005 were studied to evaluate…

Iowa Guidelines for Educationally Related Physical Therapy Services.

ERIC Educational Resources Information Center

David, Kathy

This guide provides background information to help interpret Iowa state and federal rules as they apply to physical therapy (PT) for students with disabilities (birth to age 21) in educational settings. The first section defines professional personnel requirements and statements of licensure for the positions of physical therapist and physical…

Educational Benefits of Music in an Inclusive Classroom

ERIC Educational Resources Information Center

Sze, Susan; Yu, Sanna

2004-01-01

The purpose of this study is to highlight literature concerning the effects of music therapy on children with disabilities. The paper is organized in the following sections: (1) background of music and children with disabilities, (2) the aims of music therapy, (3) main contributions to cognitive, biopsychosocial development of children with…

International survey of vestibular rehabilitation therapists by the Barany Society Ad Hoc Committee on Vestibular Rehabilitation Therapy.

PubMed

Cohen, Helen S; Gottshall, Kim R; Graziano, Mariella; Malmstrom, Eva-Maj; Sharpe, Margaret H

2009-01-01

The goal of this study was to determine how occupational and physical therapists learn about vestibular rehabilitation therapy, their educational backgrounds, referral patterns, and their ideas about entry-level and advanced continuing education in vestibular rehabilitation therapy. The Barany Society Ad Hoc Committee for Vestibular Rehabilitation Therapy invited therapists around the world to complete an E-mail survey. Participants were either known to committee members or other Barany Society members, known to other participants, identified from their self-listings on the Internet, or volunteered after reading notices published in publications read by therapists. Responses were received from 133 therapists in 19 countries. They had a range of educational backgrounds, practice settings, and referral patterns. Few respondents had had any training about vestibular rehabilitation during their professional entry-level education. Most respondents learned about vestibular rehabilitation from continuing education courses, interactions with their colleagues, and reading. All of them endorsed the concept of developing standards and educating therapists about vestibular anatomy and physiology, vestibular diagnostic testing, vestibular disorders and current intervention strategies. Therefore, the Committee recommends the development of international standards for education and practice in vestibular rehabilitation therapy.

All Might Have Won, But Not All Have the Prize: Optimal Treatment for Substance Abuse Among Adolescents with Conduct Problems

PubMed Central

Spas, Jayson; Ramsey, Susan; Paiva, Andrea L.; Stein, L.A.R.

2012-01-01

Considerable evidence from the literature on treatment outcomes indicates that substance abuse treatment among adolescents with conduct problems varies widely. Treatments commonly used among this population are cognitive-behavioral therapy (CBT), 12-step facilitation, multisystemic therapy (MST), psychoeducation (PE), and motivational interviewing (MI). This manuscript thoroughly and systematically reviews the available literature to determine which treatment is optimal for substance-abusing adolescents with conduct problems. Results suggest that although there are several evidence-based and empirically supported treatments, those that incorporate family-based intervention consistently provide the most positive treatment outcomes. In particular, this review further reveals that although many interventions have gained empirical support over the years, only one holds the prize as being the optimal treatment of choice for substance abuse treatment among adolescents with conduct problems. PMID:23170066

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

PubMed

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.

Haemodialysis in an emerging centre in a developing country: a two year review and predictors of mortality

PubMed Central

2011-01-01

Background Haemodialysis is the most common form of renal replacement therapy in Nigeria. The high cost of haemodialysis has made optimal therapy of end-stage renal disease difficult in Nigeria. This paper is a review of data collected over two years of provision of dialysis services in a new tertiary hospital in Southern Nigeria. Methods This retrospective analysis is done on data obtained from the patient case files and dialysis records in the first two years of provision of dialysis services in our centre. A gender comparison of the patients' baseline sociodemographic, clinical and biochemical was performed and a logistic regression model used to assess the predictors of mortality. Results A total of 98 patients had 471 sessions in the two years under review. Males and females had similar characteristics at baseline except for a higher median serum urea in the males. The commonest causes of end-stage renal disease were chronic glomerulonephritis (34.5%), hypertension (32.1%) and diabetes mellitus (17.9%). The main predictor of mortality was under treatment with haemodialysis due to inability to pay for more than a few dialysis sessions. Conclusions This study has highlighted the unchanging demographics of our advanced kidney failure patients. Efforts should be aimed at subsidizing the cost of dialysis for our teeming population of dialysis dependent chronic kidney disease patients. PMID:21962220

Development and testing of an optoacoustic imaging system for monitoring and guiding prostate cancer therapies

NASA Astrophysics Data System (ADS)

Spirou, Gloria M.; Vitkin, I. Alex; Wilson, B. C.; Whelan, William M.; Henrichs, Paul M.; Mehta, Ketan; Miller, Tom; Yee, Andrew; Meador, James; Oraevsky, Alexander A.

2004-07-01

Laser Optoacoustic Imaging System (LOIS) combines high tissue contrast based on the optical properties of tissue and high spatial resolution based on ultrawide-band ultrasonic detection. Patients undergoing thermal or photodynamic therapy of prostate cancer may benefit from capability of LOIS to detect and monitor treatment-induced changes in tissue optical properties and blood flow. The performance of a prototype LOIS was evaluated via 2D optoacoustic images of dye-colored objects of various shapes, small tubes with blood simulating veins and arteries, and thermally coagulated portions of chicken breasts imbedded tissue-mimicking gelatin phantoms. The optoacoustic image contrast was proportional to the ratio of the absorption coefficient between the embedded objects and the surrounding gel. The contrast of the venous blood relative to the background exceeded 250%, and the contrast of the thermally coagulated portions of flesh relative to the untreated tissue ranged between -100% to +200%, dependent on the optical wavelength. We used a 32-element optoacoustic transducer array and a novel design of low-noise preamplifiers and wide-band amplifiers to perform these studies. The system was optimized for imaging at a depth of ~50 mm. The system spatial resolution was better than 1-mm. The advantages and limitations of various signal-processing methods were investigated. LOIS demonstrates clinical potential for non- or minimally-invasive monitoring of treatment-induced tissue changes.

Dual-channel red/blue fluorescence dosimetry with broadband reflectance spectroscopic correction measures protoporphyrin IX production during photodynamic therapy of actinic keratosis

NASA Astrophysics Data System (ADS)

Kanick, Stephen Chad; Davis, Scott C.; Zhao, Yan; Hasan, Tayyaba; Maytin, Edward V.; Pogue, Brian W.; Chapman, M. Shane

2014-07-01

Dosimetry for aminolevulinic acid (ALA)-induced protoporphyrin IX (PpIX) photodynamic therapy of actinic keratosis was examined with an optimized fluorescence dosimeter to measure PpIX during treatment. While insufficient PpIX generation may be an indicator of incomplete response, there exists no standardized method to quantitate PpIX production at depths in the skin during clinical treatments. In this study, a spectrometer-based point probe dosimeter system was used to sample PpIX fluorescence from superficial (blue wavelength excitation) and deeper (red wavelength excitation) tissue layers. Broadband white light spectroscopy (WLS) was used to monitor aspects of vascular physiology and inform a correction of fluorescence for the background optical properties. Measurements in tissue phantoms showed accurate recovery of blood volume fraction and reduced scattering coefficient from WLS, and a linear response of PpIX fluorescence versus concentration down to 1.95 and 250 nM for blue and red excitations, respectively. A pilot clinical study of 19 patients receiving 1-h ALA incubation before treatment showed high intrinsic variance in PpIX fluorescence with a standard deviation/mean ratio of >0.9. PpIX fluorescence was significantly higher in patients reporting higher pain levels on a visual analog scale. These pilot data suggest that patient-specific PpIX quantitation may predict outcome response.

Dual-channel red/blue fluorescence dosimetry with broadband reflectance spectroscopic correction measures protoporphyrin IX production during photodynamic therapy of actinic keratosis

PubMed Central

Kanick, Stephen Chad; Davis, Scott C.; Zhao, Yan; Hasan, Tayyaba; Maytin, Edward V.; Pogue, Brian W.; Chapman, M. Shane

2014-01-01

Abstract. Dosimetry for aminolevulinic acid (ALA)-induced protoporphyrin IX (PpIX) photodynamic therapy of actinic keratosis was examined with an optimized fluorescence dosimeter to measure PpIX during treatment. While insufficient PpIX generation may be an indicator of incomplete response, there exists no standardized method to quantitate PpIX production at depths in the skin during clinical treatments. In this study, a spectrometer-based point probe dosimeter system was used to sample PpIX fluorescence from superficial (blue wavelength excitation) and deeper (red wavelength excitation) tissue layers. Broadband white light spectroscopy (WLS) was used to monitor aspects of vascular physiology and inform a correction of fluorescence for the background optical properties. Measurements in tissue phantoms showed accurate recovery of blood volume fraction and reduced scattering coefficient from WLS, and a linear response of PpIX fluorescence versus concentration down to 1.95 and 250 nM for blue and red excitations, respectively. A pilot clinical study of 19 patients receiving 1-h ALA incubation before treatment showed high intrinsic variance in PpIX fluorescence with a standard deviation/mean ratio of >0.9. PpIX fluorescence was significantly higher in patients reporting higher pain levels on a visual analog scale. These pilot data suggest that patient-specific PpIX quantitation may predict outcome response. PMID:24996661

At least seven days delayed stenting using minimalist immediate mechanical intervention (MIMI) in ST-segment elevation myocardial infarction: the SUPER-MIMI study.

PubMed

Mester, Petru; Bouvaist, Helene; Delarche, Nicolas; Bouisset, Frédéric; Abdellaoui, Mohamed; Petiteau, Pierre-Yves; Dubreuil, Olivier; Boueri, Ziad; Chettibi, Mohamed; Souteyrand, Géraud; Madiot, Hend; Belle, Loic

2017-07-20

The aim of this study was to ascertain whether a minimalist immediate mechanical intervention (MIMI) aiming to restore an optimal Thrombolysis In Myocardial Infarction (TIMI) flow in the culprit artery, followed ≥7 days later by a second percutaneous coronary intervention with intentional stenting, is safe in patients with ST-segment elevation myocardial infarction and large thrombotic burden. SUPER-MIMI was a prospective, observational trial conducted between January 2014 and April 2015 in 14 French centres. A total of 155 patients were enrolled. The pharmacological therapy was left to the operator's discretion. Eighty-one patients (52.3%) had glycoprotein IIb/IIIa inhibitors (GPI) initiated before the end of the first procedure. The median (interquartile range [IQR]) delay between the two procedures was eight (seven to 12) days. Infarct-related artery reocclusion between the two procedures (primary endpoint) occurred in two patients (1.3%), neither of whom received GPI treatment. TIMI flow was maintained or improved between the end of the first procedure and the beginning of the second procedure in all patients. Thrombotic burden and stenosis severity diminished significantly between the two procedures. Stents were ultimately implanted in 97 patients (62.6%). Deferred stenting (≥7 days) in patients with a high thrombus burden was safe on a background of GPI therapy.

The Role of Echocardiography in the Optimization of Cardiac Resynchronization Therapy: Current Evidence and Future Perspectives.

PubMed

Spartalis, Michael; Tzatzaki, Eleni; Spartalis, Eleftherios; Damaskos, Christos; Athanasiou, Antonios; Livanis, Efthimios; Voudris, Vassilis

2017-01-01

Cardiac resynchronization therapy (CRT) has become a mainstay in the management of heart failure. Up to one-third of patients who received resynchronization devices do not experience the full benefits of CRT. The clinical factors influencing the likelihood to respond to the therapy are wide QRS complex, left bundle branch block, female gender, non-ischaemic cardiomyopathy (highest responders), male gender, ischaemic cardiomyopathy (moderate responders) and narrow QRS complex, non-left bundle branch block (lowest, non-responders). This review provides a conceptual description of the role of echocardiography in the optimization of CRT. A literature survey was performed using PubMed database search to gather information regarding CRT and echocardiography. A total of 70 studies met selection criteria for inclusion in the review. Echocardiography helps in the initial selection of the patients with dyssynchrony, which will benefit the most from optimal biventricular pacing and provides a guide to left ventricular (LV) lead placement during implantation. Different echocardiographic parameters have shown promise and can offer the possibility of patient selection, response prediction, lead placement optimization strategies and optimization of device configurations. LV ejection fraction along with specific electrocardiographic criteria remains the cornerstone of CRT patient selection. Echocardiography is a non-invasive, cost-effective, highly reproducible method with certain limitations and accuracy that is affected by measurement errors. Echocardiography can assist with the identification of the appropriate electromechanical substrate of CRT response and LV lead placement. The targeted approach can improve the haemodynamic response, as also the patient-specific parameters estimation.

Dialectical Behavior Therapy (DBT) Applied to College Students: A Randomized Clinical Trial

ERIC Educational Resources Information Center

Pistorello, Jacqueline; Fruzzetti, Alan E.; MacLane, Chelsea; Gallop, Robert; Iverson, Katherine M.

2012-01-01

Objective: College counseling centers (CCCs) are increasingly being called upon to treat highly distressed students with complex clinical presentations. This study compared the effectiveness of Dialectical Behavior Therapy (DBT) for suicidal college students with an optimized control condition and analyzed baseline global functioning as a…

Therapy for Family Systems.

ERIC Educational Resources Information Center

Rosmann, Michael R.

A family therapy model, based on a conceptualization of the family as a behavioral system whose members interact adaptively so that an optimal level of functioning is maintained within the system, is described. The divergent roots of this conceptualization are discussed briefly, as are the treatment approaches based on it. The author's model,…

Optimizing Cognitive-Behavioral Therapy for Childhood Psychiatric Disorders

ERIC Educational Resources Information Center

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.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Novelli, Luigi, E-mail: luigi.novelli@egp.aphp.fr; Raynaud, Alain; Pellerin, Olivier

We report the case of a 50-year-old man who presented to our institution with septic thrombosis of the renal vein which had not resolved despite several days of antibiotic therapy. Optimal restoration of renal vein flow was obtained by percutaneous manual aspiration embolectomy (PMAE) in this patient with contraindication to fibrinolytic therapy and surgery.

A Randomized Placebo-Controlled Trial of D-Cycloserine for the Enhancement of Social Skills Training in Pervasive Development Disorders

DTIC Science & Technology

2015-03-01

Psychotherapy Physical Therapy Social Skills Training Music Therapy Other Treatments 12 (35.29) 9 (26.47) 1 (2.94) 0 (0.00) 3...Training Music Therapy Other Treatments 6 (40.00) 6 (40.00) 2 (13.33) 0 (0.00) 1 (6.67) 1 (6.67) 1 (6.67) 1 (6.67) 30 (57.69) 21...ASD). This study extended upon this background by combining DCS with behavioral social skills therapy in youth with ASD to assess its impact on the

Towards a hierarchical optimization modeling framework for the evaluation and construction of spatially targeted incentive policies to promote green infrastructure (GI) amidst budgetary, compliance and GI-effectiveness uncertainties

EPA Science Inventory

Background:Bilevel optimization has been recognized as a 2-player Stackelberg game where players are represented as leaders and followers and each pursue their own set of objectives. Hierarchical optimization problems, which are a generalization of bilevel, are especially difficu...

LED light design method for high contrast and uniform illumination imaging in machine vision.

PubMed

Wu, Xiaojun; Gao, Guangming

2018-03-01

In machine vision, illumination is very critical to determine the complexity of the inspection algorithms. Proper lights can obtain clear and sharp images with the highest contrast and low noise between the interested object and the background, which is conducive to the target being located, measured, or inspected. Contrary to the empirically based trial-and-error convention to select the off-the-shelf LED light in machine vision, an optimization algorithm for LED light design is proposed in this paper. It is composed of the contrast optimization modeling and the uniform illumination technology for non-normal incidence (UINI). The contrast optimization model is built based on the surface reflection characteristics, e.g., the roughness, the reflective index, and light direction, etc., to maximize the contrast between the features of interest and the background. The UINI can keep the uniformity of the optimized lighting by the contrast optimization model. The simulation and experimental results demonstrate that the optimization algorithm is effective and suitable to produce images with the highest contrast and uniformity, which is very inspirational to the design of LED illumination systems in machine vision.

He-Ne ILLLI used for brain trauma: a clinical observation of 46 cases

NASA Astrophysics Data System (ADS)

Yang, Da-Ke; Ru, Zheng-Guo; Ge, Sheng-Li; Shuo, Wei-Lan

1998-11-01

With the background that ILLLI can lower the viscosity of blood, improve the microcirculation, we investigated and compared the therapeutic effect of conventional drug therapy and ILLLI combined drug therapy for brain trauma. We found that ILLLI combined drug therapy could effectively alleviate some symptoms such as headache, vertigo, nausea, vomiting, blurred vision, anorexia caused by brain trauma. the therapeutic effect of treated group was prior to control group.

The new criterion for cardiac resynchronization therapy treatment assessed by two channels impedance cardiography

NASA Astrophysics Data System (ADS)

Peczalski, K.; Palko, T.; Wojciechowski, D.; Dunajski, Z.; Kowalewski, M.

2013-04-01

The cardiac resynchronization therapy is an effective treatment for systolic failure patients. Independent electrical stimulation of left and right ventricle corrects mechanical ventricular dyssynchrony. About 30-40% treated patients do not respond to therapy. In order to improve clinical outcome authors propose the two channels impedance cardiography for assessment of ventricular dyssynchrony. The proposed method is intended for validation of patients diagnosis and optimization of pacemaker settings for cardiac resynchronization therapy. The preliminary study has showed that bichannel impedance cardiography is a promising tool for assessment of ventricular dyssynchrony.

Novel medical therapeutics in glioblastomas, including targeted molecular therapies, current and future clinical trials.

PubMed

Quant, Eudocia C; Wen, Patrick Y

2010-08-01

The prognosis for glioblastoma is poor despite optimal therapy with surgery, radiation, and chemotherapy. New therapies that improve survival and quality of life are needed. Research has increased our understanding of the molecular pathways important for gliomagenesis and disease progression. Novel agents have been developed against these targets, including receptor tyrosine kinases, intracellular signaling molecules, epigenetic abnormalities, and tumor vasculature and microenvironment. This article reviews novel therapies for glioblastoma, with an emphasis on targeted agents. Copyright 2010 Elsevier Inc. All rights reserved.

Evolving Complexity in Hemophilia Management.

PubMed

Croteau, Stacy E

2018-06-01

Rapid expansion of therapeutic options have increased the complexity of hemophilia care. Previously, on-demand therapy aimed to reduce morbidity and early mortality; however, now aggressive prophylaxis, particularly in children, encourages an active lifestyle. Accurate diagnosis, recognition of early threats to musculoskeletal health, and optimization of therapy are critical for both males and females affected by hemophilia. The diversity of emerging hemophilia therapies, from modified factor protein concentrates, to gene therapy, to nonfactor hemostatic strategies, provide an exciting opportunity to target unmet needs in the bleeding disorder community. Copyright © 2018 Elsevier Inc. All rights reserved.

Physical reparative treatment in reptiles

PubMed Central

2013-01-01

Background The tissue growth necessary to achieve a complete or partial restitution ad integrum as a result of injury to soft tissue and/or hard times in reptiles is variable and often needs long time in relation to the species, to the habitat and to their intrinsic physiological characteristics. The purpose of this work was to see if the tissue optimization (TO) treatment with radio electric asymmetric conveyer (REAC) provided good results in these animals and whether its use translates into reduced time of tissue repair. This paper describes preliminary results with in promoting the tissue repair in reptiles. Cases presentation A 5 year old male Testudo graeca (Leo) and Trachemys scripta scripta (Mir) and a 15 year old female Testudo hermanni (Juta) were evaluated because of soft tissue injuries. A female 25 year old Trachemys scripta elegans (Ice), a female 2.5 year old Trachemys scripta scripta (Penelope) as well as a 50 year old male Testudo graeca (Margherito) were evaluated because of wounds of the carapace. Following debridement and traditional therapies, Leo, Penelope and Margherito were exposed to the radio electric asymmetric conveyer (REAC) device, with a specific treatment protocol, named tissue optimization-basic (TO-B). Also Ice and Mir were subjected to REAC treatment after wounds debridement. Juta was treated only with REAC treatment. Complete wound healing was evident after 17 days for Leo, 7 days for Penelope, 27 days for Mir, 78 days for Ice and after 14 days for Margherito. Juta showed a considerable tissue activation in 2 days and complete wound healing in 5 days. Conclusion Our findings suggest that REAC TO-B treatment may provide advantages over other traditional methods after complete wound healing in Leo, and also suitable healing in the other patients. Then REAC device with its specific treatment TO-B protocol, which induces tissue repair without causing severe stress to the patient, could be a potential therapy for tissue damage healing in reptiles. Further studies still need to be conducted to support our observations. PMID:23442770

Novel and optimized strategies for inducing fibrosis in vivo: focus on Duchenne Muscular Dystrophy

PubMed Central

2014-01-01

Background Fibrosis, an excessive collagen accumulation, results in scar formation, impairing function of vital organs and tissues. Fibrosis is a hallmark of muscular dystrophies, including the lethal Duchenne muscular dystrophy (DMD), which remains incurable. Substitution of muscle by fibrotic tissue also complicates gene/cell therapies for DMD. Yet, no optimal models to study muscle fibrosis are available. In the widely used mdx mouse model for DMD, extensive fibrosis develops in the diaphragm only at advanced adulthood, and at about two years of age in the ‘easy-to-access’ limb muscles, thus precluding fibrosis research and the testing of novel therapies. Methods We developed distinct experimental strategies, ranging from chronic exercise to increasing muscle damage on limb muscles of young mdx mice, by myotoxin injection, surgically induced trauma (laceration or denervation) or intramuscular delivery of profibrotic growth factors (such as TGFβ). We also extended these approaches to muscle of normal non-dystrophic mice. Results These strategies resulted in advanced and enhanced muscle fibrosis in young mdx mice, which persisted over time, and correlated with reduced muscle force, thus mimicking the severe DMD phenotype. Furthermore, increased fibrosis was also obtained by combining these procedures in muscles of normal mice, mirroring aberrant repair after severe trauma. Conclusions We have developed new and improved experimental strategies to accelerate and enhance muscle fibrosis in vivo. These strategies will allow rapidly assessing fibrosis in the easily accessible limb muscles of young mdx mice, without necessarily having to use old animals. The extension of these fibrogenic regimes to the muscle of non-dystrophic wild-type mice will allow fibrosis assessment in a wide array of pre-existing transgenic mouse lines, which in turn will facilitate understanding the mechanisms of fibrogenesis. These strategies should improve our ability to combat fibrosis-driven dystrophy progression and aberrant regeneration. PMID:25157321

Barriers and Facilitators of Adherence to Antiretroviral Drug Therapy and Retention in Care among Adult HIV-Positive Patients: A Qualitative Study from Ethiopia

PubMed Central

Bezabhe, Woldesellassie M.; Chalmers, Leanne; Bereznicki, Luke R.; Peterson, Gregory M.; Bimirew, Mekides A.; Kassie, Desalew M.

2014-01-01

Background Antiretroviral therapy (ART) has been life saving for hundreds of thousands of Ethiopians. With increased availability of ART in recent years, achievement of optimal adherence and patient retention are becoming the greatest challenges in the management of HIV/AIDS in Ethiopia. However, few studies have explored factors influencing medication adherence to ART and retention in follow-up care among adult Ethiopian HIV-positive patients, especially in the Amhara region of the country, where almost one-third of the country’s ART is prescribed. The aim of this qualitative study was to collect such data from patients and healthcare providers in the Amhara region of Ethiopia. Methods Semi-structured interviews were conducted with 24 patients, of whom 11 had been lost to follow-up and were non-persistent with ART. In addition, focus group discussions were performed with 15 ART nurses and 19 case managers. All interviews and focus groups were audio-recorded, transcribed, and coded for themes and patterns in Amharic using a grounded theory approach. The emergent concepts and categories were translated into English. Results Economic constraints, perceived stigma and discrimination, fasting, holy water, medication side effects, and dissatisfaction with healthcare services were major reasons for patients being non-adherent and lost to follow-up. Disclosure of HIV status, social support, use of reminder aids, responsibility for raising children, improved health on ART, and receiving education and counseling emerged as facilitators of adherence to ART. Conclusions Improving adherence and retention requires integration of enhanced treatment access with improved job and food security. Healthcare providers need to be supported to better equip patients to cope with the issues associated with ART. Development of social policies and cooperation between various agencies are required to facilitate optimal adherence to ART, patient retention, and improved patient outcomes. PMID:24828585

Aerobic Exercise for Reducing Migraine Burden: Mechanisms, Markers, and Models of Change Processes

PubMed Central

Irby, Megan B.; Bond, Dale S.; Lipton, Richard B.; Nicklas, Barbara; Houle, Timothy T.; Penzien, Donald B.

2016-01-01

Background Engagement in regular exercise routinely is recommended as an intervention for managing and preventing migraine, and yet empirical support is far from definitive. We possess at best a weak understanding of how aerobic exercise and resulting change in aerobic capacity influence migraine, let alone the optimal parameters for exercise regimens as migraine therapy (eg, who will benefit, when to prescribe, optimal types, and doses/intensities of exercise, level of anticipated benefit). These fundamental knowledge gaps critically limit our capacity to deploy exercise as an intervention for migraine. Overview Clear articulation of the markers and mechanisms through which aerobic exercise confers benefits for migraine would prove invaluable and could yield insights on migraine pathophysiology. Neurovascular and neuroinflammatory pathways, including an effect on obesity or adiposity, are obvious candidates for study given their role both in migraine as well as the changes known to accrue with regular exercise. In addition to these biological pathways, improvements in aerobic fitness and migraine alike also are mediated by changes in psychological and sociocognitive factors. Indeed a number of specific mechanisms and pathways likely are operational in the relationship between exercise and migraine improvement, and it remains to be established whether these pathways operate in parallel or synergistically. As heuristics that might conceptually benefit our research programs here forward, we: (1) provide an extensive listing of potential mechanisms and markers that could account for the effects of aerobic exercise on migraine and are worthy of empirical exploration and (2) present two exemplar conceptual models depicting pathways through which exercise may serve to reduce the burden of migraine. Conclusion Should the promise of aerobic exercise as a feasible and effective migraine therapy be realized, this line of endeavor stands to benefit migraineurs (including the many who presently remain suboptimally treated) by providing a new therapeutic avenue as an alternative or augmentative compliment to established interventions for migraine. PMID:26643584

Prevention of VTE in Orthopedic Surgery Patients

PubMed Central

Francis, Charles W.; Johanson, Norman A.; Curley, Catherine; Dahl, Ola E.; Schulman, Sam; Ortel, Thomas L.; Pauker, Stephen G.; Colwell, Clifford W.

2012-01-01

Background: VTE is a serious, but decreasing complication following major orthopedic surgery. This guideline focuses on optimal prophylaxis to reduce postoperative pulmonary embolism and DVT. Methods: The methods of this guideline follow those described in Methodology for the Development of Antithrombotic Therapy and Prevention of Thrombosis Guidelines: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines in this supplement. Results: In patients undergoing major orthopedic surgery, we recommend the use of one of the following rather than no antithrombotic prophylaxis: low-molecular-weight heparin; fondaparinux; dabigatran, apixaban, rivaroxaban (total hip arthroplasty or total knee arthroplasty but not hip fracture surgery); low-dose unfractionated heparin; adjusted-dose vitamin K antagonist; aspirin (all Grade 1B); or an intermittent pneumatic compression device (IPCD) (Grade 1C) for a minimum of 10 to 14 days. We suggest the use of low-molecular-weight heparin in preference to the other agents we have recommended as alternatives (Grade 2C/2B), and in patients receiving pharmacologic prophylaxis, we suggest adding an IPCD during the hospital stay (Grade 2C). We suggest extending thromboprophylaxis for up to 35 days (Grade 2B). In patients at increased bleeding risk, we suggest an IPCD or no prophylaxis (Grade 2C). In patients who decline injections, we recommend using apixaban or dabigatran (all Grade 1B). We suggest against using inferior vena cava filter placement for primary prevention in patients with contraindications to both pharmacologic and mechanical thromboprophylaxis (Grade 2C). We recommend against Doppler (or duplex) ultrasonography screening before hospital discharge (Grade 1B). For patients with isolated lower-extremity injuries requiring leg immobilization, we suggest no thromboprophylaxis (Grade 2B). For patients undergoing knee arthroscopy without a history of VTE, we suggest no thromboprophylaxis (Grade 2B). Conclusions: Optimal strategies for thromboprophylaxis after major orthopedic surgery include pharmacologic and mechanical approaches. PMID:22315265

Adjuvant Lapatinib and Trastuzumab for Early Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer: Results From the Randomized Phase III Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization Trial

PubMed Central

Holmes, Eileen; Baselga, José; de Azambuja, Evandro; Dueck, Amylou C.; Viale, Giuseppe; Zujewski, Jo Anne; Goldhirsch, Aron; Armour, Alison; Pritchard, Kathleen I.; McCullough, Ann E.; Dolci, Stella; McFadden, Eleanor; Holmes, Andrew P.; Tonghua, Liu; Eidtmann, Holger; Dinh, Phuong; Di Cosimo, Serena; Harbeck, Nadia; Tjulandin, Sergei; Im, Young-Hyuck; Huang, Chiun-Sheng; Diéras, Véronique; Hillman, David W.; Wolff, Antonio C.; Jackisch, Christian; Lang, Istvan; Untch, Michael; Smith, Ian; Boyle, Frances; Xu, Binghe; Gomez, Henry; Suter, Thomas; Gelber, Richard D.; Perez, Edith A.

2016-01-01

Background Lapatinib (L) plus trastuzumab (T) improves outcomes for metastatic human epidermal growth factor 2–positive breast cancer and increases the pathologic complete response in the neoadjuvant setting, but their role as adjuvant therapy remains uncertain. Methods In the Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization trial, patients with centrally confirmed human epidermal growth factor 2–positive early breast cancer were randomly assigned to 1 year of adjuvant therapy with T, L, their sequence (T→L), or their combination (L+T). The primary end point was disease-free survival (DFS), with 850 events required for 80% power to detect a hazard ratio (HR) of 0.8 for L+T versus T. Results Between June 2007 and July 2011, 8,381 patients were enrolled. In 2011, due to futility to demonstrate noninferiority of L versus T, the L arm was closed, and patients free of disease were offered adjuvant T. A protocol modification required P ≤ .025 for the two remaining pairwise comparisons. At a protocol-specified analysis with a median follow-up of 4.5 years, a 16% reduction in the DFS hazard rate was observed with L+T compared with T (555 DFS events; HR, 0.84; 97.5% CI, 0.70 to 1.02; P = .048), and a 4% reduction was observed with T→L compared with T (HR, 0.96; 97.5% CI, 0.80 to 1.15; P = .61). L-treated patients experienced more diarrhea, cutaneous rash, and hepatic toxicity compared with T-treated patients. The incidence of cardiac toxicity was low in all treatment arms. Conclusion Adjuvant treatment that includes L did not significantly improve DFS compared with T alone and added toxicity. One year of adjuvant T remains standard of care. PMID:26598744

Adenovirus-Associated Virus Vector–Mediated Gene Transfer in Hemophilia B

PubMed Central

Nathwani, Amit C.; Tuddenham, Edward G.D.; Rangarajan, Savita; Rosales, Cecilia; McIntosh, Jenny; Linch, David C.; Chowdary, Pratima; Riddell, Anne; Pie, Arnulfo Jaquilmac; Harrington, Chris; O’Beirne, James; Smith, Keith; Pasi, John; Glader, Bertil; Rustagi, Pradip; Ng, Catherine Y.C.; Kay, Mark A.; Zhou, Junfang; Spence, Yunyu; Morton, Christopher L.; Allay, James; Coleman, John; Sleep, Susan; Cunningham, John M.; Srivastava, Deokumar; Basner-Tschakarjan, Etiena; Mingozzi, Federico; High, Katherine A.; Gray, John T.; Reiss, Ulrike M.; Nienhuis, Arthur W.; Davidoff, Andrew M.

2012-01-01

BACKGROUND Hemophilia B, an X-linked disorder, is ideally suited for gene therapy. We investigated the use of a new gene therapy in patients with the disorder. METHODS We infused a single dose of a serotype-8–pseudotyped, self-complementary adenovirus-associated virus (AAV) vector expressing a codon-optimized human factor IX (FIX) transgene (scAAV2/8-LP1-hFIXco) in a peripheral vein in six patients with severe hemophilia B (FIX activity, <1% of normal values). Study participants were enrolled sequentially in one of three cohorts (given a high, intermediate, or low dose of vector), with two participants in each group. Vector was administered without immunosuppressive therapy, and participants were followed for 6 to 16 months. RESULTS AAV-mediated expression of FIX at 2 to 11% of normal levels was observed in all participants. Four of the six discontinued FIX prophylaxis and remained free of spontaneous hemorrhage; in the other two, the interval between prophylactic injections was increased. Of the two participants who received the high dose of vector, one had a transient, asymptomatic elevation of serum aminotransferase levels, which was associated with the detection of AAV8-capsid–specific T cells in the peripheral blood; the other had a slight increase in liver-enzyme levels, the cause of which was less clear. Each of these two participants received a short course of glucocorticoid therapy, which rapidly normalized aminotransferase levels and maintained FIX levels in the range of 3 to 11% of normal values. CONCLUSIONS Peripheral-vein infusion of scAAV2/8-LP1-hFIXco resulted in FIX transgene expression at levels sufficient to improve the bleeding phenotype, with few side effects. Although immune-mediated clearance of AAV-transduced hepatocytes remains a concern, this process may be controlled with a short course of glucocorticoids without loss of transgene expression. (Funded by the Medical Research Council and others; ClinicalTrials.gov number, NCT00979238.) PMID:22149959

Efficacy of second-line antiretroviral therapy among people living with HIV/AIDS in Asia: Results from the TREAT Asia HIV Observational Database

PubMed Central

BOETTIGER, David C; NGUYEN, Van Kinh; DURIER, Nicolas; BUI, Huy Vu; SIM, Benedict Lim Heng; AZWA, Iskandar; LAW, Matthew; RUXRUNGTHAM, Kiat

2014-01-01

Background Roughly 4% of the 1.25 million patients on antiretroviral therapy (ART) in Asia are using second-line therapy. To maximize patient benefit and regional resources it is important to optimize the timing of second-line ART initiation and use the most effective compounds available. Methods HIV positive patients enrolled in the TREAT Asia HIV Observational Database who had used second-line ART for ≥6 months were included. ART use and rates and predictors of second-line treatment failure were evaluated. Results There were 302 eligible patients. Most were male (76.5%) and exposed to HIV via heterosexual contact (71.5%). Median age at second-line initiation was 39.2 years, median CD4 cell count was 146 cells/mm3, and median HIV viral load was 16,224 copies/mL. Patients started second-line ART before 2007 (n=105), 2007-2010 (n=147) and after 2010 (n=50). Ritonavir-boosted lopinavir and atazanavir accounted for the majority of protease inhibitor use after 2006. Median follow-up time on second-line was 2.3 years. The rates of treatment failure and mortality per 100 patient/years were 8.8 (95%CI 7.1 to 10.9) and 1.1 (95%CI 0.6 to 1.9), respectively. Older age, high baseline viral load and use of a protease inhibitor other than lopinavir or atazanavir were associated with a significantly shorter time to second-line failure. Conclusions Increased access to viral load monitoring to facilitate early detection of first-line ART failure and subsequent treatment switch is important for maximizing the durability of second-line therapy in Asia. Although second-line ART is highly effective in the region, the reported rate of failure emphasizes the need for third-line ART in a small portion of patients. PMID:25590271

Is belief larger than fact: expectations, optimism and reality for translational stem cell research

PubMed Central

2012-01-01

Background Stem cell (SC) therapies hold remarkable promise for many diseases, but there is a significant gulf between public expectations and the reality of progress toward clinical application. Public expectations are fueled by stakeholder arguments for research and public funding, coupled with intense media coverage in an ethically charged arena. We examine media representations in light of the expanding global landscape of SC clinical trials, asking what patients may realistically expect by way of timelines for the therapeutic and curative potential of regenerative medicine? Methods We built 2 international datasets: (1) 3,404 clinical trials (CT) containing 'stem cell*' from ClinicalTrials.gov and the World Health Organization's International Clinical Trials Registry Search Portal; and (2) 13,249 newspaper articles on SC therapies using Factiva.com. We compared word frequencies between the CT descriptions and full-text newspaper articles for the number containing terms for SC type and diseases/conditions. We also developed inclusion and exclusion criteria to identify novel SC CTs, mainly regenerative medicine applications. Results Newspaper articles focused on human embryonic SCs and neurological conditions with significant coverage as well of cardiovascular disease and diabetes. In contrast, CTs used primarily hematopoietic SCs, with an increase in CTs using mesenchymal SCs since 2007. The latter dominated our novel classification for CTs, most of which are in phases I and II. From the perspective of the public, expecting therapies for neurological conditions, there is limited activity in what may be considered novel applications of SC therapies. Conclusions Given the research, regulatory, and commercialization hurdles to the clinical translation of SC research, it seems likely that patients and political supporters will become disappointed and disillusioned. In this environment, proponents need to make a concerted effort to temper claims. Even though the field is highly promising, it lacks significant private investment and is largely reliant on public support, requiring a more honest acknowledgement of the expected therapeutic benefits and the timelines to achieving them. PMID:23131007

Evidence-based recommendations for the use of topical oxygen therapy in the treatment of lower extremity wounds.

PubMed

Gordillo, Gayle M; Sen, Chandan K

2009-06-01

Topical oxygen therapy provides another tool in the armamentarium of clinicians treating refractory lower extremity wounds. Devices suitable for providing topical oxygen therapy in a clinical setting have recently become available. This article reviews the evidence to justify the use of this treatment modality, including in vitro, preclinical data, and clinical data. It also provides a protocol for how to administer topical oxygen therapy as well as guidance on patient selection and management to optimize outcomes. Randomized controlled trials are not yet reported and clearly necessary. The current body of evidence suggests that topical oxygen therapy may be considered as a second line of therapy for refractory wounds.

Therapeutics: Alpha-1 Antitrypsin Augmentation Therapy.

PubMed

Campos, Michael; Lascano, Jorge

2017-01-01

Subjects with alpha-1 antitrypsin deficiency who develop pulmonary disease are managed following general treatment guidelines, including disease management interventions. In addition, administration of intravenous infusions of alpha-1 proteinase inhibitor (augmentation therapy) at regular schedules is a specific therapy for individuals with AATD with pulmonary involvement.This chapter summarizes the manufacturing differences of commercially available formulations and the available evidence of the effects of augmentation therapy. Biologically, there is clear evidence of in vivo local antiprotease effects in the lung and systemic immunomodulatory effects. Clinically, there is cumulative evidence of slowing lung function decline and emphysema progression. The optimal dose of augmentation therapy is being revised as well as more individualized assessment of who needs this therapy.

Resectable Pediatric Nonrhabdomyosarcoma Soft Tissue Sarcoma: Which Patients Benefit from Adjuvant Radiation Therapy and How Much?

PubMed Central

Million, Lynn; Donaldson, Sarah S.

2012-01-01

It remains unclear which children and adolescents with resected nonrhabdomyosarcoma soft tissue sarcoma (NRSTS) benefit from radiation therapy, as well as the optimal dose, volume, and timing of radiotherapy when used with primary surgical resection. This paper reviews the sparse literature from clinical trials and retrospective studies of resected pediatric NRSTS to discern local recurrence rates in relationship to the use of radiation therapy. PMID:22523704

Redesigning Radiotherapy Quality Assurance: Opportunities to Develop an Efficient, Evidence-Based System to Support Clinical Trials

PubMed Central

Bekelman, Justin E.; Deye, James A.; Vikram, Bhadrasain; Bentzen, Soren M.; Bruner, Deborah; Curran, Walter J.; Dignam, James; Efstathiou, Jason A.; FitzGerald, T. J.; Hurkmans, Coen; Ibbott, Geoffrey S.; Lee, J. Jack; Merchant, Timothy E.; Michalski, Jeff; Palta, Jatinder R.; Simon, Richard; Ten Haken, Randal K.; Timmerman, Robert; Tunis, Sean; Coleman, C. Norman; Purdy, James

2012-01-01

Background In the context of national calls for reorganizing cancer clinical trials, the National Cancer Institute (NCI) sponsored a two day workshop to examine the challenges and opportunities for optimizing radiotherapy quality assurance (QA) in clinical trial design. Methods Participants reviewed the current processes of clinical trial QA and noted the QA challenges presented by advanced technologies. Lessons learned from the radiotherapy QA programs of recent trials were discussed in detail. Four potential opportunities for optimizing radiotherapy QA were explored, including the use of normal tissue toxicity and tumor control metrics, biomarkers of radiation toxicity, new radiotherapy modalities like proton beam therapy, and the international harmonization of clinical trial QA. Results Four recommendations were made: 1) Develop a tiered (and more efficient) system for radiotherapy QA and tailor intensity of QA to clinical trial objectives. Tiers include (i) general credentialing, (ii) trial specific credentialing, and (iii) individual case review; 2) Establish a case QA repository; 3) Develop an evidence base for clinical trial QA and introduce innovative prospective trial designs to evaluate radiotherapy QA in clinical trials; and 4) Explore the feasibility of consolidating clinical trial QA in the United States. Conclusion Radiotherapy QA may impact clinical trial accrual, cost, outcomes and generalizability. To achieve maximum benefit, QA programs must become more efficient and evidence-based. PMID:22425219

Research and the promotion of child health: a position paper of the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition.

PubMed

Koletzko, Berthold; Kolacek, Sanja; Phillips, Alan; Troncone, Riccardo; Vandenplas, Yvan; Thapar, Nikhil; Baumann, Ulrich; van Goudoever, Johannes; Mihatsch, Walter; de Swarte, Casper; Benninga, Marc; Mearin, Luisa

2014-08-01

Children comprise one-fifth of Europe's population. Promoting child health and development is of key importance for society and its future. This position paper highlights opportunities of investing in gastrointestinal, liver, and nutritional research to promote child health and delineates priorities for research. Investing in child health plays a key role in the promotion of population health, well-being, and disease prevention lifelong, with large health economic benefits. Major opportunities for improving knowledge and translational application arise from recent scientific and technological developments, for example, the long-term impact of early environmental cues interacting with genes. Personalised approaches to therapy and prevention should be enhanced. Deciphering the microbiome and its effects on functions can help in promoting long-term health. Epigenetic research can help to understand how early environmental factors influence later gastrointestinal and hepatic health and disease. A linked nutrition and physical activity strategy can promote health and prevent nutritional deficiencies, inactivity, and chronic noncommunicable diseases, such as diabetes, to ensure optimal health and cognition. Special attention should be devoted to populations with low socioeconomic status, migrant background, and ethnic minorities, and to critical life periods, including pregnancy, lactation, infancy, and childhood. Improved understanding of optimal nutrition and on maintaining gut and liver homeostasis throughout childhood will help prevent chronic diseases in later life.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

NONE

The physical pattern of energy deposition and the enhanced relative biological effectiveness (RBE) of protons and carbon ions compared to photons offer unique and not fully understood or exploited opportunities to improve the efficacy of radiation therapy. Variations in RBE within a pristine or spread out Bragg peak and between particle types may be exploited to enhance cell killing in target regions without a corresponding increase in damage to normal tissue structures. In addition, the decreased sensitivity of hypoxic tumors to photon-based therapies may be partially overcome through the use of more densely ionizing radiations. These and other differences betweenmore » particle and photon beams may be used to generate biologically optimized treatments that reduce normal tissue complications. In this symposium, speakers will examine the impact of the RBE of charged particles on measurable biological endpoints, treatment plan optimization, and the prediction or retrospective assessment of treatment outcomes. In particular, an AAPM task group was formed to critically examine the evidence for a spatially-variant RBE in proton therapy. Current knowledge of proton RBE variation with respect to dose, biological endpoint, and physics parameters will be reviewed. Further, the clinical relevance of these variations will be discussed. Recent work focused on improving simulations of radiation physics and biological response in proton and carbon ion therapy will also be presented. Finally, relevant biology research and areas of research needs will be highlighted, including the dependence of RBE on genetic factors including status of DNA repair pathways, the sensitivity of cancer stem-like cells to charged particles, the role of charged particles in hypoxic tumors, and the importance of fractionation effects. In addition to the physical advantages of protons and more massive ions over photons, the future application of biologically optimized treatment plans and their potential to provide higher levels of local tumor control and improved normal tissue sparing will be discussed. Learning Objectives: To assess whether the current practice of a constant RBE of 1.1 should be revised or maintained in proton therapy and to evaluate the potential clinical consequences of delivering RBE-weighted dose distributions based on variable RBE To review current research on biological models used to predict the increased biological effectiveness of proton and carbon ions to help move towards a practical understanding and implementation of biological optimization in particle therapy To discuss potential differences in biological mechanisms between photons and charged particles (light and heavy ions) that could impact clinical cancer therapy H. Paganetti, NCI U19 CA21239D. Grosshans, Our research is supported by the NCIK. Held, Funding Support: National Cancer Institute of the National Institutes of Health, USA, under Award Number R21CA182259 and Federal Share of Program Income Earned by Massachusetts General Hospital on C06CA059267, Proton Therapy Research and Treatment Center.« less

Influence of robust optimization in intensity-modulated proton therapy with different dose delivery techniques

PubMed Central

Liu, Wei; Li, Yupeng; Li, Xiaoqiang; Cao, Wenhua; Zhang, Xiaodong

2012-01-01

Purpose: The distal edge tracking (DET) technique in intensity-modulated proton therapy (IMPT) allows for high energy efficiency, fast and simple delivery, and simple inverse treatment planning; however, it is highly sensitive to uncertainties. In this study, the authors explored the application of DET in IMPT (IMPT-DET) and conducted robust optimization of IMPT-DET to see if the planning technique’s sensitivity to uncertainties was reduced. They also compared conventional and robust optimization of IMPT-DET with three-dimensional IMPT (IMPT-3D) to gain understanding about how plan robustness is achieved. Methods: They compared the robustness of IMPT-DET and IMPT-3D plans to uncertainties by analyzing plans created for a typical prostate cancer case and a base of skull (BOS) cancer case (using data for patients who had undergone proton therapy at our institution). Spots with the highest and second highest energy layers were chosen so that the Bragg peak would be at the distal edge of the targets in IMPT-DET using 36 equally spaced angle beams; in IMPT-3D, 3 beams with angles chosen by a beam angle optimization algorithm were planned. Dose contributions for a number of range and setup uncertainties were calculated, and a worst-case robust optimization was performed. A robust quantification technique was used to evaluate the plans’ sensitivity to uncertainties. Results: With no uncertainties considered, the DET is less robust to uncertainties than is the 3D method but offers better normal tissue protection. With robust optimization to account for range and setup uncertainties, robust optimization can improve the robustness of IMPT plans to uncertainties; however, our findings show the extent of improvement varies. Conclusions: IMPT’s sensitivity to uncertainties can be improved by using robust optimization. They found two possible mechanisms that made improvements possible: (1) a localized single-field uniform dose distribution (LSFUD) mechanism, in which the optimization algorithm attempts to produce a single-field uniform dose distribution while minimizing the patching field as much as possible; and (2) perturbed dose distribution, which follows the change in anatomical geometry. Multiple-instance optimization has more knowledge of the influence matrices; this greater knowledge improves IMPT plans’ ability to retain robustness despite the presence of uncertainties. PMID:22755694

Constraining neutron guide optimizations with phase-space considerations

NASA Astrophysics Data System (ADS)

Bertelsen, Mads; Lefmann, Kim

2016-09-01

We introduce a method named the Minimalist Principle that serves to reduce the parameter space for neutron guide optimization when the required beam divergence is limited. The reduced parameter space will restrict the optimization to guides with a minimal neutron intake that are still theoretically able to deliver the maximal possible performance. The geometrical constraints are derived using phase-space propagation from moderator to guide and from guide to sample, while assuming that the optimized guides will achieve perfect transport of the limited neutron intake. Guide systems optimized using these constraints are shown to provide performance close to guides optimized without any constraints, however the divergence received at the sample is limited to the desired interval, even when the neutron transport is not limited by the supermirrors used in the guide. As the constraints strongly limit the parameter space for the optimizer, two control parameters are introduced that can be used to adjust the selected subspace, effectively balancing between maximizing neutron transport and avoiding background from unnecessary neutrons. One parameter is needed to describe the expected focusing abilities of the guide to be optimized, going from perfectly focusing to no correlation between position and velocity. The second parameter controls neutron intake into the guide, so that one can select exactly how aggressively the background should be limited. We show examples of guides optimized using these constraints which demonstrates the higher signal to noise than conventional optimizations. Furthermore the parameter controlling neutron intake is explored which shows that the simulated optimal neutron intake is close to the analytically predicted, when assuming that the guide is dominated by multiple scattering events.

Why is it not working? Identifying barriers to the therapy of paediatric obesity in an intercultural setting.

PubMed

Ciupitu, Carmen Cristina; Babitsch, Birgit

2011-06-01

Given the high overweight prevalence among children with a migration background in Germany, this paper describes barriers to the treatment of paediatric obesity in a specialized clinic providing services to an ethnically diverse population. In a cross-sectional mixed-method design, a two-week participant observation was followed by a cultural competence survey among the healthcare professionals employed at the clinic. The present study revealed barriers related to all categories of social actors involved in the therapy process. A major difficulty encountered by providers when working with ethnically diverse patients was the lack of mutual understanding, often associated with language barriers. Language barriers were most prevalent between providers and ethnically diverse mothers. Targeted education programs for adults (particularly women) with a migration background and cultural competence training for healthcare providers are needed in Germany. Special attention should be paid to scheduling appointments and enhancing patients' engagement in the therapy process.

Dendritic Immunotherapy Improvement for an Optimal Control Murine Model

PubMed Central

Chimal-Eguía, J. C.; Castillo-Montiel, E.

2017-01-01

Therapeutic protocols in immunotherapy are usually proposed following the intuition and experience of the therapist. In order to deduce such protocols mathematical modeling, optimal control and simulations are used instead of the therapist's experience. Clinical efficacy of dendritic cell (DC) vaccines to cancer treatment is still unclear, since dendritic cells face several obstacles in the host environment, such as immunosuppression and poor transference to the lymph nodes reducing the vaccine effect. In view of that, we have created a mathematical murine model to measure the effects of dendritic cell injections admitting such obstacles. In addition, the model considers a therapy given by bolus injections of small duration as opposed to a continual dose. Doses timing defines the therapeutic protocols, which in turn are improved to minimize the tumor mass by an optimal control algorithm. We intend to supplement therapist's experience and intuition in the protocol's implementation. Experimental results made on mice infected with melanoma with and without therapy agree with the model. It is shown that the dendritic cells' percentage that manages to reach the lymph nodes has a crucial impact on the therapy outcome. This suggests that efforts in finding better methods to deliver DC vaccines should be pursued. PMID:28912828

Dosimetric advantages of IMPT over IMRT for laser-accelerated proton beams

NASA Astrophysics Data System (ADS)

Luo, W.; Li, J.; Fourkal, E.; Fan, J.; Xu, X.; Chen, Z.; Jin, L.; Price, R.; Ma, C.-M.

2008-12-01

As a clinical application of an exciting scientific breakthrough, a compact and cost-efficient proton therapy unit using high-power laser acceleration is being developed at Fox Chase Cancer Center. The significance of this application depends on whether or not it can yield dosimetric superiority over intensity-modulated radiation therapy (IMRT). The goal of this study is to show how laser-accelerated proton beams with broad energy spreads can be optimally used for proton therapy including intensity-modulated proton therapy (IMPT) and achieve dosimetric superiority over IMRT for prostate cancer. Desired energies and spreads with a varying δE/E were selected with the particle selection device and used to generate spread-out Bragg peaks (SOBPs). Proton plans were generated on an in-house Monte Carlo-based inverse-planning system. Fifteen prostate IMRT plans previously used for patient treatment have been included for comparison. Identical dose prescriptions, beam arrangement and consistent dose constrains were used for IMRT and IMPT plans to show the dosimetric differences that were caused only by the different physical characteristics of proton and photon beams. Different optimization constrains and beam arrangements were also used to find optimal IMPT. The results show that conventional proton therapy (CPT) plans without intensity modulation were not superior to IMRT, but IMPT can generate better proton plans if appropriate beam setup and optimization are used. Compared to IMRT, IMPT can reduce the target dose heterogeneity ((D5-D95)/D95) by up to 56%. The volume receiving 65 Gy and higher (V65) for the bladder and the rectum can be reduced by up to 45% and 88%, respectively, while the volume receiving 40 Gy and higher (V40) for the bladder and the rectum can be reduced by up to 49% and 68%, respectively. IMPT can also reduce the whole body non-target tissue dose by up to 61% or a factor 2.5. This study has shown that the laser accelerator under development has a potential to generate high-quality proton beams for cancer treatment. Significant improvement in target dose uniformity and normal tissue sparing as well as in reduction of whole body dose can be achieved by IMPT with appropriate optimization and beam setup.

Optimal Therapy Scheduling Based on a Pair of Collaterally Sensitive Drugs.

PubMed

Yoon, Nara; Vander Velde, Robert; Marusyk, Andriy; Scott, Jacob G

2018-05-07

Despite major strides in the treatment of cancer, the development of drug resistance remains a major hurdle. One strategy which has been proposed to address this is the sequential application of drug therapies where resistance to one drug induces sensitivity to another drug, a concept called collateral sensitivity. The optimal timing of drug switching in these situations, however, remains unknown. To study this, we developed a dynamical model of sequential therapy on heterogeneous tumors comprised of resistant and sensitive cells. A pair of drugs (DrugA, DrugB) are utilized and are periodically switched during therapy. Assuming resistant cells to one drug are collaterally sensitive to the opposing drug, we classified cancer cells into two groups, [Formula: see text] and [Formula: see text], each of which is a subpopulation of cells resistant to the indicated drug and concurrently sensitive to the other, and we subsequently explored the resulting population dynamics. Specifically, based on a system of ordinary differential equations for [Formula: see text] and [Formula: see text], we determined that the optimal treatment strategy consists of two stages: an initial stage in which a chosen effective drug is utilized until a specific time point, T, and a second stage in which drugs are switched repeatedly, during which each drug is used for a relative duration (i.e., [Formula: see text]-long for DrugA and [Formula: see text]-long for DrugB with [Formula: see text] and [Formula: see text]). We prove that the optimal duration of the initial stage, in which the first drug is administered, T, is shorter than the period in which it remains effective in decreasing the total population, contrary to current clinical intuition. We further analyzed the relationship between population makeup, [Formula: see text], and the effect of each drug. We determine a critical ratio, which we term [Formula: see text], at which the two drugs are equally effective. As the first stage of the optimal strategy is applied, [Formula: see text] changes monotonically to [Formula: see text] and then, during the second stage, remains at [Formula: see text] thereafter. Beyond our analytic results, we explored an individual-based stochastic model and presented the distribution of extinction times for the classes of solutions found. Taken together, our results suggest opportunities to improve therapy scheduling in clinical oncology.

Detection of Foreign Matter in Transfusion Solution Based on Gaussian Background Modeling and an Optimized BP Neural Network

PubMed Central

Zhou, Fuqiang; Su, Zhen; Chai, Xinghua; Chen, Lipeng

2014-01-01

This paper proposes a new method to detect and identify foreign matter mixed in a plastic bottle filled with transfusion solution. A spin-stop mechanism and mixed illumination style are applied to obtain high contrast images between moving foreign matter and a static transfusion background. The Gaussian mixture model is used to model the complex background of the transfusion image and to extract moving objects. A set of features of moving objects are extracted and selected by the ReliefF algorithm, and optimal feature vectors are fed into the back propagation (BP) neural network to distinguish between foreign matter and bubbles. The mind evolutionary algorithm (MEA) is applied to optimize the connection weights and thresholds of the BP neural network to obtain a higher classification accuracy and faster convergence rate. Experimental results show that the proposed method can effectively detect visible foreign matter in 250-mL transfusion bottles. The misdetection rate and false alarm rate are low, and the detection accuracy and detection speed are satisfactory. PMID:25347581

Nanodosimetry-Based Plan Optimization for Particle Therapy

PubMed Central

Schulte, Reinhard W.

2015-01-01

Treatment planning for particle therapy is currently an active field of research due uncertainty in how to modify physical dose in order to create a uniform biological dose response in the target. A novel treatment plan optimization strategy based on measurable nanodosimetric quantities rather than biophysical models is proposed in this work. Simplified proton and carbon treatment plans were simulated in a water phantom to investigate the optimization feasibility. Track structures of the mixed radiation field produced at different depths in the target volume were simulated with Geant4-DNA and nanodosimetric descriptors were calculated. The fluences of the treatment field pencil beams were optimized in order to create a mixed field with equal nanodosimetric descriptors at each of the multiple positions in spread-out particle Bragg peaks. For both proton and carbon ion plans, a uniform spatial distribution of nanodosimetric descriptors could be obtained by optimizing opposing-field but not single-field plans. The results obtained indicate that uniform nanodosimetrically weighted plans, which may also be radiobiologically uniform, can be obtained with this approach. Future investigations need to demonstrate that this approach is also feasible for more complicated beam arrangements and that it leads to biologically uniform response in tumor cells and tissues. PMID:26167202

Tolerability and Healthcare Utilization in Maintenance Hemodialysis Patients Undergoing Treatment for Tuberculosis-Related Conditions

PubMed Central

Hamadah, Abdurrahman M.; Beaulieu, Lynn M.; Wilson, John W.; Aksamit, Timothy R.; Gregoire, James R.; Williams, Amy W.; Dillon, John J.; Albright, Robert C.; Onuigbo, Macaulay; Iyer, Venkateshwaran K.; Hickson, LaTonya J.

2016-01-01

Background The incidence of tuberculosis in end-stage renal disease is significantly higher than the general population. Among those with kidney dysfunction, anti-tuberculosis treatment is associated with increased side effects, but the effect on healthcare utilization is unknown. Methods/Aim To assess patient-reported symptoms, adverse effects and describe changes in healthcare utilization patterns during treatment for tuberculosis, we conducted a case series (n=12) of patients receiving maintenance hemodialysis from Mayo Clinic Dialysis Services and concurrent drug therapy for tuberculosis from January 2002 through May 2014. Healthcare utilization (hospitalizations and emergency department visits independent of hospital admission) was compared before and during treatment. Results Patients were treated for latent (n=7) or active (n=5) tuberculosis. The majority of patients with latent disease were treated with isoniazid (n=5, 71%), while active-disease patients received a 4-drug regimen. Adverse effects were reported in 83% of patients. Compared to measurements prior to drug initiation, serum albumin and dialysis weights were similar at 3 months. Commonly reported anti-tuberculosis drug toxicities were described. More than half (58%) of patients were hospitalized at least once. No emergency department or hospital admissions occurred in the period prior to drug therapy, but healthcare utilization increased during treatment in the latent disease group (hospitalization rate per person-month: pre, 0 vs. post, 1). Conclusions Among hemodialysis patients, anti-tuberculosis therapy is associated with frequent patient-reported symptoms and increased healthcare utilization. Patients receiving treatment for latent disease may have the greatest increase in healthcare use. Careful monitoring and early complication detection may help optimize medication adherence and minimize hospitalizations. PMID:26859893

Gene polymorphisms in folate metabolizing enzymes in adult acute lymphoblastic leukemia: effects on methotrexate-related toxicity and survival

PubMed Central

Ongaro, Alessia; De Mattei, Monica; Della Porta, Matteo Giovanni; Rigolin, GianMatteo; Ambrosio, Cristina; Di Raimondo, Francesco; Pellati, Agnese; Masieri, Federica Francesca; Caruso, Angelo; Catozzi, Linda; Gemmati, Donato

2009-01-01

Background The antifolate agent methotrexate is an important component of maintenance therapy in acute lymphoblastic leukemia, although methotrexate-related toxicity is often a reason for interruption of chemotherapy. Prediction of toxicity is difficult because of inter-individual variability susceptibility to antileukemic agents. Methotrexate interferes with folate metabolism leading to depletion of reduced folates. Design and Methods The aim of this study was to investigate the influence of polymorphisms for folate metabolizing enzymes with respect to toxicity and survival in adult patients with acute lymphoblastic leukemia treated with methotrexate maintenance therapy. To this purpose, we evaluated possible associations between genotype and hematologic and non-hematologic toxicity and effects on survival at 2 years of follow-up in patients with acute lymphoblastic leukemia. Results Polymorphisms in the genes encoding for methylenetetrahydrofolate reductase (MTHFR 677C>T) and in dihydrofolate reductase (DHFR 19 bp deletion) significantly increased the risk of hepatotoxicity in single (odds ratio 5.23, 95% confidence interval 1.13–21.95 and odds ratio 4.57, 95% confidence interval 1.01–20.77, respectively) and in combined analysis (odds ratio 6.82, 95% confidence interval 1.38–33.59). MTHFR 677C>T also increased the risk of leukopenia and gastrointestinal toxicity, whilst thymidylate synthase 28 bp repeat polymorphism increased the risk of anemia (odds ratio 8.48, 95% confidence interval 2.00–36.09). Finally, patients with MTHFR 677TT had a decreased overall survival rate (hazard ratio 2.37, 95% confidence interval 1.46–8.45). Conclusions Genotyping of folate polymorphisms might be useful in adult acute lymphoblastic leukemia to optimize methotrexate therapy, reducing the associated toxicity with possible effects on survival. PMID:19648163

Peginterferon alfa‐2a (40KD) plus ribavirin in chronic hepatitis C patients who failed previous interferon therapy

PubMed Central

Sherman, M; Yoshida, E M; Deschenes, M; Krajden, M; Bain, V G; Peltekian, K; Anderson, F; Kaita, K; Simonyi, S; Balshaw, R; Lee, S S

2006-01-01

Background The management of patients with chronic hepatitis C who have relapsed or failed to respond to interferon based therapies is an important issue facing hepatologists. Aims We evaluated the efficacy and safety of peginterferon alfa‐2a (40KD) plus ribavirin in this population by conducting a multicentre open label study. Patients Data from adults with detectable serum hepatitis C virus (HCV) RNA who had not responded or had relapsed after previous conventional interferon or conventional interferon/ribavirin combination therapy were analysed. Methods Patients were retreated with peginterferon alfa‐2a (40KD) 180 µg/week plus ribavirin 800 mg/day for 24 or 48 weeks at the investigators' discretion. The study was conceived before the optimal dose of ribavirin (1000/1200 mg/day) for patients with genotype 1 was known. The primary endpoint was sustained virological response (SVR), defined as undetectable HCV RNA (<50 IU/ml) after 24 weeks of follow up. The analysis was conducted by intention to treat. Results A total of 312 patients (212 non‐responders, 100 relapsers) were included. Of these, 28 patients were treated for 24 weeks and 284 for 48 weeks. Baseline characteristics between non‐responders and relapsers were similar although more non‐responders had genotype 1 infection (87% v 69%). Overall SVR rates were 23% (48/212) for non‐responders and 41% (41/100) for relapsers. When data were analysed by genotype, SVR rates were 24% (61/253) in genotype 1 and 47% (28/59) in genotype 2/3. Conclusions These results in a large patient cohort demonstrate that it is possible to cure a proportion of previous non‐responders and relapsers by retreating with peginterferon alfa‐2a (40KD) plus ribavirin. PMID:16709661

Optimization of Clonazepam Therapy Adjusted to Patient’s CYP3A Status and NAT2 Genotype

PubMed Central

Tóth, Katalin; Csukly, Gábor; Sirok, Dávid; Belic, Ales; Kiss, Ádám; Háfra, Edit; Déri, Máté; Menus, Ádám; Bitter, István

2016-01-01

Background: The shortcomings of clonazepam therapy include tolerance, withdrawal symptoms, and adverse effects such as drowsiness, dizziness, and confusion leading to increased risk of falls. Inter-individual variability in the incidence of adverse events in patients partly originates from the differences in clonazepam metabolism due to genetic and nongenetic factors. Methods: Since the prominent role in clonazepam nitro-reduction and acetylation of 7-amino-clonazepam is assigned to CYP3A and N-acetyl transferase 2 enzymes, respectively, the association between the patients’ CYP3A status (CYP3A5 genotype, CYP3A4 expression) or N-acetyl transferase 2 acetylator phenotype and clonazepam metabolism (plasma concentrations of clonazepam and 7-amino-clonazepam) was evaluated in 98 psychiatric patients suffering from schizophrenia or bipolar disorders. Results: The patients’ CYP3A4 expression was found to be the major determinant of clonazepam plasma concentrations normalized by the dose and bodyweight (1263.5±482.9 and 558.5±202.4ng/mL per mg/kg bodyweight in low and normal expressers, respectively, P<.0001). Consequently, the dose requirement for the therapeutic concentration of clonazepam was substantially lower in low-CYP3A4 expresser patients than in normal expressers (0.029±0.011 vs 0.058±0.024mg/kg bodyweight, P<.0001). Furthermore, significantly higher (about 2-fold) plasma concentration ratio of 7-amino-clonazepam and clonazepam was observed in the patients displaying normal CYP3A4 expression and slower N-acetylation than all the others. Conclusion: Prospective assaying of CYP3A4 expression and N-acetyl transferase 2 acetylator phenotype can better identify the patients with higher risk of adverse reactions and can facilitate the improvement of personalized clonazepam therapy and withdrawal regimen. PMID:27639091

Clinical Outcomes After the Nonoperative Management of Lateral Patellar Dislocations: A Systematic Review

PubMed Central

Moiz, Munim; Smith, Nick; Smith, Toby O.; Chawla, Amit; Thompson, Peter; Metcalfe, Andrew

2018-01-01

Background: The first-line treatment for patellar dislocations is often nonoperative and consists of physical therapy and immobilization techniques, with various adjuncts employed. However, the outcomes of nonoperative therapy are poorly described, and there is a lack of quality evidence to define the optimal intervention. Purpose: To perform a comprehensive review of the literature and assess the quality of studies presenting patient outcomes from nonoperative interventions for patellar dislocations. Study Design: Systematic review; Level of evidence, 4. Methods: The MEDLINE, AMED, Embase, CINAHL, Cochrane Library, PEDro, and SPORTDiscus electronic databases were searched through July 2017 by 3 independent reviewers. The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines were followed. Study quality was assessed using the CONSORT (Consolidated Standards for Reporting Trials) criteria for randomized controlled trials and the Newcastle-Ottawa Scale for cohort studies and case series. Results: A total of 25 studies met our inclusion criteria, including 12 randomized controlled trials, 7 cohort studies, and 6 case series, consisting of 1066 patients. Studies were grouped according to 4 broad categories of nonoperative interventions based on immobilization, weightbearing status, quadriceps exercise type, and alternative therapies. The most commonly used outcome measure was the Kujala score, and the pooled redislocation rate was 31%. Conclusion: This systematic review found that patient-reported outcomes consistently improved after all methods of treatment but did not return to normal. Redislocation rates were high and close to the redislocation rates reported in natural history studies. There is a lack of quality evidence to advocate the use of any particular nonoperative technique for the treatment of patellar dislocations. PMID:29942814

Treatment Strategies in Octogenarians with Early-Stage, High-Risk Breast Cancer

PubMed Central

Mamtani, Anita; Gonzalez, Julie J.; Neo, Dayna T.; Friedman, Robb S.; Recht, Abram; Hacker, Michele R.; Sharma, Ranjna

2018-01-01

Background Octogenarians with early-stage breast cancer often have low-risk tumor biology. However, optimal treatment strategies for those with high-risk biology remain unclear. Methods We reviewed the records of women ages 80–89 years with biopsy-proven, Stage I–II invasive breast cancer who were referred for surgical evaluation from January 2001 through December 2010. High-risk was defined as human epidermal growth factor receptor-positive (HER2+), triple-negative (TN), or histologic grade 3 disease. Results Among 178 patients, 40 (22%) were high-risk: 12 were grade 1–2 (10 HER2 +, 2 TN); 28 were grade 3 (7 HER2+, 6 TN, 15 estrogen receptor-positive (ER+)/HER2−). The high-risk group had larger tumors and more often had ductal histology and lymphovascular invasion than the low-risk group and was more likely to undergo mastectomy (18 vs. 5%, p = 0.02), radiotherapy (55 vs. 36%, p = 0.03), and chemotherapy (10 vs. 0%, p = 0.002). Endocrine therapy use was similar among ER+ patients in both groups. The four patients in the high-risk group given chemotherapy were HER2+ and received trastuzumab-based regimens, without any reported toxicities. At median follow-up of 67 months, 10% of the high-risk group had a recurrence (3 distant-only, 1 simultaneous locoregional and distant in a patient treated with mastectomy without radiotherapy). Conclusions Tailored locoregional and systemic therapy resulted in low incidence of failure in these octogenarians with high-risk cancers with low morbidity. Modern adjuvant therapies should be considered for elderly women with high-risk cancers in the absence of significant comorbidities. PMID:29427213

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

PubMed

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 < .0001), and higher baseline optimism predicted a faster decline in 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.

Breaking down patient and physician barriers to optimize glycemic control in type 2 diabetes.

PubMed

Ross, Stuart A

2013-09-01

Approximately half of patients with type 2 diabetes (T2D) do not achieve globally recognized blood glucose targets, despite the availability of a wide range of effective glucose-lowering therapies. Failure to maintain good glycemic control increases the risk of diabetes-related complications and long-term health care costs. Patients must be brought under glycemic control to improve treatment outcomes, but existing barriers to optimizing glycemic control must first be overcome, including patient nonadherence to treatment, the failure of physicians to intensify therapy in a timely manner, and inadequacies in the health care system itself. The reasons for such barriers include treatment side effects, complex treatment regimens, needle anxiety, poor patient education, and the absence of an adequate patient care plan; however, newer therapies and devices, combined with comprehensive care plans involving adequate patient education, can help to minimize barriers and improve treatment outcomes. Copyright © 2013 Elsevier Inc. All rights reserved.

Role of Physical Therapists in Reducing Hospital Readmissions: Optimizing Outcomes for Older Adults During Care Transitions From Hospital to Community.

PubMed

Falvey, Jason R; Burke, Robert E; Malone, Daniel; Ridgeway, Kyle J; McManus, Beth M; Stevens-Lapsley, Jennifer E

2016-08-01

Hospital readmissions in older adult populations are an emerging quality indicator for acute care hospitals. Recent evidence has linked functional decline during and after hospitalization with an elevated risk of hospital readmission. However, models of care that have been developed to reduce hospital readmission rates do not adequately address functional deficits. Physical therapists, as experts in optimizing physical function, have a strong opportunity to contribute meaningfully to care transition models and demonstrate the value of physical therapy interventions in reducing readmissions. Thus, the purposes of this perspective article are: (1) to describe the need for physical therapist input during care transitions for older adults and (2) to outline strategies for expanding physical therapy participation in care transitions for older adults, with an overall goal of reducing avoidable 30-day hospital readmissions. © 2016 American Physical Therapy Association.

Defining the possibilities: is short duration treatment of chronic hepatitis C genotype 1 with sofosbuvir-containing regimens likely to be as effective as current regimens?

PubMed

Nafisi, Shirin; Roy, Sabyasachi; Gish, Robert; Manch, Richard; Kohli, Anita

2016-01-01

This review summarizes published data on sofosbuvir-based regimens for patients infected with HCV GT1 with a focus on evaluating the optimal and possible durations of treatment. PubMed and conference abstract books published between 2011-2015 were searched. HCV treatment has decreased from 24 week regimens to studies done as short as 4 weeks. History of prior treatment or cirrhosis have consistently shown lower SVR12 rates with shorter duration therapies. Low cure rates have been seen in patients within 4 week trials, however, select patients with low fibrosis scores, low HCV VL and HCV GT-1b have moderate cure rates. Most patients will require 12-24 weeks of therapy. Further studies are needed to elucidate the predictors of treatment response to short duration therapies and optimal combination of DAAs.

Amplifying the Red-Emission of Upconverting Nanoparticles for Biocompatible Clinically Used Prodrug-Induced Photodynamic Therapy

DOE PAGES

Punjabi, Amol; Wu, Xiang; Tokatli-Apollon, Amira; ...

2014-09-25

A class of biocompatible upconverting nanoparticles (UCNPs) with largely amplified red-emissions was developed. The optimal UCNP shows a high absolute upconversion quantum yield of 3.2% in red-emission, which is 15-fold stronger than the known optimal β-phase core/shell UCNPs. When conjugated to aminolevulinic acid, a clinically used photodynamic therapy (PDT) prodrug, significant PDT effect in tumor was demonstrated in a deep-tissue (>1.2 cm) setting in vivo at a biocompatible laser power density. Furthermore, we show that our UCNP–PDT system with NIR irradiation outperforms clinically used red light irradiation in a deep tumor setting in vivo. This study marks a major stepmore » forward in photodynamic therapy utilizing UCNPs to effectively access deep-set tumors.Lastly, it also provides an opportunity for the wide application of upconverting red radiation in photonics and biophotonics.« less

Supportive care for children with cancer. Guidelines of the Childrens Cancer Study Group. The use of nutritional therapy.

PubMed

Lukens, J N

1984-01-01

Nutritional support for children with cancer is predicated on the belief that optimal nutrition promotes tolerance of anti-neoplastic therapy and preserves immunologic responsiveness. The use of nutritional support is based on the assumption that there is effective therapy for the primary disease and that there will be a predictable period of nutritional stress. The most common nutritional problem is posed by the failure of sick children willingly to eat enough to maintain nutritional homeostasis. Supplementation of oral intake with a nutritional formula given by a small-bore nasogastric tube is simple, effective, and economical. If the sum of oral and tolerated nasogastric tube feedings is less than that required for optimal nutrition, unmet needs may be satisfied by nutrients given into a peripheral vein. Total parenteral nutrition, given by central vein, is reserved for situations in which the combination of enteral and peripheral venous alimentation is inadequate.

Process change evaluation framework for allogeneic cell therapies: impact on drug development and commercialization.

PubMed

Hassan, Sally; Huang, Hsini; Warren, Kim; Mahdavi, Behzad; Smith, David; Jong, Simcha; Farid, Suzanne S

2016-04-01

Some allogeneic cell therapies requiring a high dose of cells for large indication groups demand a change in cell expansion technology, from planar units to microcarriers in single-use bioreactors for the market phase. The aim was to model the optimal timing for making this change. A development lifecycle cash flow framework was created to examine the implications of process changes to microcarrier cultures at different stages of a cell therapy's lifecycle. The analysis performed under assumptions used in the framework predicted that making this switch earlier in development is optimal from a total expected out-of-pocket cost perspective. From a risk-adjusted net present value view, switching at Phase I is economically competitive but a post-approval switch can offer the highest risk-adjusted net present value as the cost of switching is offset by initial market penetration with planar technologies. The framework can facilitate early decision-making during process development.

Myocardial Viability: From Proof of Concept to Clinical Practice

PubMed Central

Tan, Timothy C.; Hsu, Chijen; Denniss, Alan Robert

2016-01-01

Ischaemic left ventricular (LV) dysfunction can arise from myocardial stunning, hibernation, or necrosis. Imaging modalities have become front-line methods in the assessment of viable myocardial tissue, with the aim to stratify patients into optimal treatment pathways. Initial studies, although favorable, lacked sufficient power and sample size to provide conclusive outcomes of viability assessment. Recent trials, including the STICH and HEART studies, have failed to confer prognostic benefits of revascularisation therapy over standard medical management in ischaemic cardiomyopathy. In lieu of these recent findings, assessment of myocardial viability therefore should not be the sole factor for therapy choice. Optimization of medical therapy is paramount, and physicians should feel comfortable in deferring coronary revascularisation in patients with coronary artery disease with reduced LV systolic function. Newer trials are currently underway and will hopefully provide a more complete understanding of the pathos and management of ischaemic cardiomyopathy. PMID:27313943

The future of epigenetic therapy in solid tumours--lessons from the past.

PubMed

Azad, Nilofer; Zahnow, Cynthia A; Rudin, Charles M; Baylin, Stephen B

2013-05-01

The promise of targeting epigenetic abnormalities for cancer therapy has not been realized for solid tumours, although increasing evidence is demonstrating its worth in haematological malignancies. In fact, true clinical efficacy in haematopoietic-related neoplasms has only become evident at low doses of epigenetic-targeting drugs (namely, inhibitors of histone deacetylase and DNA methyltransferases). Describing data from preclinical studies and early clinical trial results, we hypothesize that in using low-dose epigenetic-modulating agents, tumour cells can be reprogrammed, which overrides any immediate cytotoxic and off-target effect observed at high dose. We suggest that such optimization of drug dosing and scheduling of currently available agents could give these agents a prominent place in cancer management--when used alone or in combination with other therapies. If so, optimal use of these known agents might also pave the way for the introduction of other agents that target the epigenome.

Amplifying the red-emission of upconverting nanoparticles for biocompatible clinically used prodrug-induced photodynamic therapy.

PubMed

Punjabi, Amol; Wu, Xiang; Tokatli-Apollon, Amira; El-Rifai, Mahmoud; Lee, Hyungseok; Zhang, Yuanwei; Wang, Chao; Liu, Zhuang; Chan, Emory M; Duan, Chunying; Han, Gang

2014-10-28

A class of biocompatible upconverting nanoparticles (UCNPs) with largely amplified red-emissions was developed. The optimal UCNP shows a high absolute upconversion quantum yield of 3.2% in red-emission, which is 15-fold stronger than the known optimal β-phase core/shell UCNPs. When conjugated to aminolevulinic acid, a clinically used photodynamic therapy (PDT) prodrug, significant PDT effect in tumor was demonstrated in a deep-tissue (>1.2 cm) setting in vivo at a biocompatible laser power density. Furthermore, we show that our UCNP-PDT system with NIR irradiation outperforms clinically used red light irradiation in a deep tumor setting in vivo. This study marks a major step forward in photodynamic therapy utilizing UCNPs to effectively access deep-set tumors. It also provides an opportunity for the wide application of upconverting red radiation in photonics and biophotonics.