Knee osteoarthritis pain in the elderly can be reduced by massage therapy, yoga and tai chi: A review.

PubMed

Field, Tiffany

2016-02-01

This is a review of recently published research, both empirical studies and meta-analyses, on the effects of complementary therapies including massage therapy, yoga and tai chi on pain associated with knee osteoarthritis in the elderly. The massage therapy protocols have been effective in not only reducing pain but also in increasing range of motion, specifically when moderate pressure massage was used and when both the quadriceps and hamstrings were massaged. The yoga studies typically measured pain by the WOMAC. Most of those studies showed a clinically significant reduction in pain, especially the research that focused on poses (e.g. the Iyengar studies) as opposed to those that had integrated protocols (poses, breathing and meditation exercises). The tai chi studies also assessed pain by self-report on the WOMAC and showed significant reductions in pain. The tai chi studies were difficult to compare because of their highly variable protocols in terms of the frequency and duration of treatment. Larger, randomized control trials are needed on each of these therapies using more standardized protocols and more objective variables in addition to the self-reported WOMAC pain scale, for example, range-of-motion and observed range-of-motion pain. In addition, treatment comparison studies should be conducted so, for example, if the lower-cost yoga and tai chi were as effective as massage therapy, they might be used in combination with or as supplemental to massage therapy. Nonetheless, these therapies are at least reducing pain in knee osteoarthritis and they do not seem to have side effects. Copyright © 2016 Elsevier Ltd. All rights reserved.

Therapeutic administration of atomoxetine combined with rTMS and occupational therapy for upper limb hemiparesis after stroke: a case series study of three patients.

PubMed

Kinoshita, Shoji; Kakuda, Wataru; Yamada, Naoki; Momosaki, Ryo; Okuma, Ryo; Watanabe, Shu; Abo, Masahiro

2016-03-01

Atomoxetine, a selective noradrenaline reuptake inhibitor, has been reported to enhance brain plasticity, but has not yet been used in stroke patients. We reported the feasibility and clinical benefits on motor functional recovery of the combination of repetitive transcranial magnetic stimulation (rTMS) and intensive occupational therapy (OT) in stroke patients. This pilot study was designed to evaluate the additive effects of oral atomoxetine to rTMS/OT in post-stroke hemiparetic patients. The study included three post-stroke patients with upper limb hemiparesis. Treatment with 40 mg/day atomoxetine commenced 2 weeks before admission. After confirming tolerance, the dose was increased to 120 mg/day. Low-frequency rTMS/OT was provided daily for 15 days during continued atomoxetine therapy. Motor function of the affected upper limb was evaluated with the Fugl-Meyer Assessment and Wolf Motor Function test. All patients completed the protocol and showed motor improvement up to 4 weeks after the treatment. No atomoxetine-related side effects were noted. Our protocol of triple therapy of atomoxetine, low-frequency rTMS, and OT is safe and feasible intervention for upper limb hemiparesis after stroke.

Intracavitary moderator balloon combined with 252Cf brachytherapy and boron neutron capture therapy, improving dosimetry in brain tumour and infiltrations

PubMed Central

Brandão, S F

2015-01-01

Objective: This article proposes a combination of californium-252 (252Cf) brachytherapy, boron neutron capture therapy (BNCT) and an intracavitary moderator balloon catheter applied to brain tumour and infiltrations. Methods: Dosimetric evaluations were performed on three protocol set-ups: 252Cf brachytherapy combined with BNCT (Cf-BNCT); Cf-BNCT with a balloon catheter filled with light water (LWB) and the same set-up with heavy water (HWB). Results: Cf-BNCT-HWB has presented dosimetric advantages to Cf-BNCT-LWB and Cf-BNCT in infiltrations at 2.0–5.0 cm from the balloon surface. However, Cf-BNCT-LWB has shown superior dosimetry up to 2.0 cm from the balloon surface. Conclusion: Cf-BNCT-HWB and Cf-BNCT-LWB protocols provide a selective dose distribution for brain tumour and infiltrations, mainly further from the 252Cf source, sparing the normal brain tissue. Advances in knowledge: Malignant brain tumours grow rapidly and often spread to adjacent brain tissues, leading to death. Improvements in brain radiation protocols have been continuously achieved; however, brain tumour recurrence is observed in most cases. Cf-BNCT-LWB and Cf-BNCT-HWB represent new modalities for selectively combating brain tumour infiltrations and metastasis. PMID:25927876

Nephrogenic diabetes insipidus: treat with caution.

PubMed

Boussemart, Thierry; Nsota, Jacqueline; Martin-Coignard, Dominique; Champion, Gérard

2009-09-01

Current therapy for congenital nephrogenic diabetes insipidus consists of appropriate water intake coupled with decreased urine output obtained by means of a low-sodium diet and a combination of thiazide diuretics with renal prostaglandins inhibitors or amiloride. We report a case of congenital nephrogenic diabetes insipidus that was complicated by paradoxical water intoxication secondary to liberal water intake and the initiation of hydrochlorothiazide and indomethacin combination therapy. This report emphasizes the importance of evaluating the water balance and of a quick response with strict protocols following the initiation of indomethacin and thiazide diuretics in nephrogenic diabetes insipidus.

Optical spectroscopy of radiotherapy and photodynamic therapy responses in normal rat skin shows vascular breakdown products

NASA Astrophysics Data System (ADS)

Teles de Andrade, Cintia; Nogueira, Marcelo S.; Kanick, Stephen C.; Marra, Kayla; Gunn, Jason; Andreozzi, Jacqueline; Samkoe, Kimberley S.; Kurachi, Cristina; Pogue, Brian W.

2016-03-01

Photodynamic therapy (PDT) and radiotherapy are non-systemic cancer treatment options with different mechanisms of damage. So combining these techniques has been shown to have some synergy, and can mitigate their limitations such as low PDT light penetration or radiotherapy side effects. The present study monitored the induced tissue changes after PDT, radiotherapy, and a combination protocol in normal rat skin, using an optical spectroscopy system to track the observed biophysical changes. The Wistar rats were treated with one of the protocols: PDT followed by radiotherapy, PDT, radiotherapy and radiotherapy followed by PDT. Reflectance spectra were collected in order to observe the effects of these combined therapies, especially targeting vascular response. From the reflectance, information about oxygen saturation, met-hemoglobin and bilirubin concentration, blood volume fraction (BVF) and vessel radius were extracted from model fitting of the spectra. The rats were monitored for 24 hours after treatment. Results showed that there was no significant variation in the vessel size or BVF after the treatments. However, the PDT caused a significant increase in the met-hemoglobin and bilirubin concentrations, indicating an important blood breakdown. These results may provide an important clue on how the damage establishment takes place, helping to understand the effect of the combination of those techniques in order to verify the existence of a known synergistic effect.

Greater than 95% success with 14-day bismuth quadruple anti- Helicobacter pylori therapy: a pilot study in US Hispanics.

PubMed

Salazar, Cesar O; Cardenas, Victor M; Reddy, Rita K; Dominguez, Delfina C; Snyder, Lindsey K; Graham, David Y

2012-10-01

A combination capsule of bismuth, metronidazole, and tetracycline plus omeprazole given as 10-day therapy has an overall effectiveness of 92-93% in per-protocol analysis (Grade B) with eradication of 86-91% of metronidazole-resistant Helicobacter pylori. This study aimed to explore whether extending the duration to 14 days would improve overall effectiveness per protocol to ≥95% (Grade A) in a population in which metronidazole resistance was anticipated to exist. A one-arm, open-label pilot study of H. pylori-infected, asymptomatic/mildly dyspeptic adults, Hispanic residents of El Paso, Texas, received a 14-day course of omeprazole, plus the combination capsule. We cultured and Gram-stained specimens obtained using a minimally invasive orogastric brush. Helicobacter pylori status was determined by (13)C-urea breath test at 4 or more weeks post-therapy. Forty-seven subjects (7 men and 40 women, average age 42 years) were entered. The per-protocol effectiveness was 97.1% (33/34) (95% mid-P CI: 86.3, 99.9); 100% of metronidazole-resistant strains were eradicated. Side effects were mild and self-limited but contributed to nonadherence. Therapy taken for <10 days was more likely to result in eradication failure (p < .001). Office-based orogastric brushing was well tolerated; positive cultures were obtained in 95%. Gram staining showed H. pylori-like forms in all specimens. This pilot study supports the concept that 14-day OBMT therapy is likely to be more efficacious for H. pylori eradication (Grade A, PP basis) than a 10-day course where metronidazole resistance is suspected. If confirmed, 14 days should be recommended in populations where metronidazole resistance is common. © 2012 Blackwell Publishing Ltd.

Recent Advances in Cancer Therapy Based on Dual Mode Gold Nanoparticles

PubMed Central

Spyratou, Ellas; Makropoulou, Mersini; Sihver, Lembit

2017-01-01

Many tumor-targeted strategies have been used worldwide to limit the side effects and improve the effectiveness of therapies, such as chemotherapy, radiotherapy (RT), etc. Biophotonic therapy modalities comprise very promising alternative techniques for cancer treatment with minimal invasiveness and side-effects. These modalities use light e.g., laser irradiation in an extracorporeal or intravenous mode to activate photosensitizer agents with selectivity in the target tissue. Photothermal therapy (PTT) is a minimally invasive technique for cancer treatment which uses laser-activated photoabsorbers to convert photon energy into heat sufficient to induce cells destruction via apoptosis, necroptosis and/or necrosis. During the last decade, PTT has attracted an increased interest since the therapy can be combined with customized functionalized nanoparticles (NPs). Recent advances in nanotechnology have given rise to generation of various types of NPs, like gold NPs (AuNPs), designed to act both as radiosensitizers and photothermal sensitizing agents due to their unique optical and electrical properties i.e., functioning in dual mode. Functionalized AuNPS can be employed in combination with non-ionizing and ionizing radiation to significantly improve the efficacy of cancer treatment while at the same time sparing normal tissues. Here, we first provide an overview of the use of NPs for cancer therapy. Then we review many recent advances on the use of gold NPs in PTT, RT and PTT/RT based on different types of AuNPs, irradiation conditions and protocols. We refer to the interaction mechanisms of AuNPs with cancer cells via the effects of non-ionizing and ionizing radiations and we provide recent existing experimental data as a baseline for the design of optimized protocols in PTT, RT and PTT/RT combined treatment. PMID:29257070

Analysis of a novel protocol of combined induction chemotherapy and concurrent chemoradiation in unresected non-small-cell lung cancer: a ten-year experience with vinblastine, Cisplatin, and radiation therapy.

PubMed

Waters, Eugenie; Dingle, Brian; Rodrigues, George; Vincent, Mark; Ash, Robert; Dar, Rashid; Inculet, Richard; Kocha, Walter; Malthaner, Richard; Sanatani, Michael; Stitt, Larry; Yaremko, Brian; Younus, Jawaid; Yu, Edward

2010-07-01

The London Regional Cancer Program (LRCP) uses a unique schedule of induction plus concurrent chemoradiation, termed VCRT (vinblastine, cisplatin, and radiation therapy), for the treatment of a subset of unresectable stage IIIA and IIIB non-small-cell lung cancer (NSCLC). This analysis was conducted to better understand the outcomes in VCRT-treated patients. We report a retrospective analysis of a large cohort of patients who underwent VCRT at the LRCP over a 10-year period, from 1996 to 2006. The analysis focused on OS, toxicities, and the outcomes from completion surgery in a small subset of patients. A total of 294 patients were included and 5-year OS, determined using Kaplan-Meier methodology, was 19.8% with a MST of 18.2 months. Reported grade 3-4 toxicities included neutropenia (39%), anemia (10%), pneumonitis (1%), and esophagitis (3%). Significant differences in survival between groups of patients were demonstrated with log-rank tests for completion surgery, use of radiation therapy, and cisplatin dose. Similarly, Univariate Cox regression showed that completion surgery, use of radiation therapy, cisplatin dose, and vinblastine dose were associated with increased survival. This retrospective analysis of a large cohort of patients reveals an OS for VCRT comparable to that reported in the literature for other current combined chemoradiation protocols. The success of this protocol seems to be dose dependent and the outcomes in those who underwent completion surgery suggests that pathologic complete remission is possible for IIIA and IIIB NSCLC.

Investigational treatment suspension and enhanced cell-mediated immunity at rebound followed by drug-free remission of simian AIDS

PubMed Central

2013-01-01

Background HIV infection persists despite antiretroviral treatment (ART) and is reignited as soon as therapies are suspended. This vicious cycle is fueled by the persistence of viral reservoirs that are invulnerable to standard ART protocols, and thus therapeutic agents able to target these reservoirs are needed. One such agent, auranofin, has recently been shown to decrease the memory T-cell reservoir in chronically SIVmac251-infected macaques. Moreover, auranofin could synergize with a fully suppressive ART protocol and induce a drug-free post-therapy containment of viremia. Results We administered buthionine sulfoximine (BSO), an inhibitor of glutathione synthesis currently in clinical trials for cancer, in combination with auranofin to chronically SIVmac251-infected macaques under highly-intensified ART (H-iART). The ART/auranofin/BSO therapeutic protocol was followed, after therapy suspension, by a significant decrease of viral RNA and DNA in peripheral blood as compared to pre-therapy levels. Drug-free post-therapy control of the infection was achieved in animals with pre-therapy viral loads ranging from values comparable to average human set points to levels largely higher. This control was dependent on the presence CD8+ cells and associated with enhanced levels of cell-mediated immune responses. Conclusions The level of post-therapy viral set point reduction achieved in this study is the largest reported so far in chronically SIVmac251-infected macaques and may represent a promising strategy to improve over the current “ART for life” plight. PMID:23866829

Self-Delivering RNAi Targeting PD-1 Improves Tumor-Specific T Cell Functionality for Adoptive Cell Therapy of Malignant Melanoma.

PubMed

Ligtenberg, Maarten A; Pico de Coaña, Yago; Shmushkovich, Taisia; Yoshimoto, Yuya; Truxova, Iva; Yang, Yuan; Betancur-Boissel, Monica; Eliseev, Alexey V; Wolfson, Alexey D; Kiessling, Rolf

2018-06-06

Adoptive cell therapy (ACT) is becoming a prominent alternative therapeutic treatment for cancer patients relapsing on traditional therapies. In parallel, antibodies targeting immune checkpoint molecules, such as cytotoxic-T-lymphocyte-associated antigen 4 (CTLA-4) and cell death protein 1 pathway (PD-1), are rapidly being approved for multiple cancer types, including as first line therapy for PD-L1-expressing non-small-cell lung cancer. The combination of ACT and checkpoint blockade could substantially boost the efficacy of ACT. In this study, we generated a novel self-delivering small interfering RNA (siRNA) (sdRNA) that knocked down PD-1 expression on healthy donor T cells as well as patient-derived tumor-infiltrating lymphocytes (TIL). We have developed an alternative chemical modification of RNA backbone for improved stability and increased efficacy. Our results show that T cells treated with sdRNA specific for PD-1 had increased interferon γ (IFN-γ) secreting capacity and that this modality of gene expression interference could be utilized in our rapid expansion protocol for production of TIL for therapy. TIL expanded in the presence of PD-1-specific sdRNA performed with increased functionality against autologous tumor as compared to control TIL. This method of introducing RNAi into T cells to modify the expression of proteins could easily be adopted into any ACT protocol and will lead to the exploration of new combination therapies. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

FAST INdiCATE Trial protocol. Clinical efficacy of functional strength training for upper limb motor recovery early after stroke: neural correlates and prognostic indicators.

PubMed

Pomeroy, Valerie M; Ward, Nick S; Johansen-Berg, Heidi; van Vliet, Paulette; Burridge, Jane; Hunter, Susan M; Lemon, Roger N; Rothwell, John; Weir, Christopher J; Wing, Alan; Walker, Andrew A; Kennedy, Niamh; Barton, Garry; Greenwood, Richard J; McConnachie, Alex

2014-02-01

Functional strength training in addition to conventional physical therapy could enhance upper limb recovery early after stroke more than movement performance therapy plus conventional physical therapy. To determine (a) the relative clinical efficacy of conventional physical therapy combined with functional strength training and conventional physical therapy combined with movement performance therapy for upper limb recovery; (b) the neural correlates of response to conventional physical therapy combined with functional strength training and conventional physical therapy combined with movement performance therapy; (c) whether any one or combination of baseline measures predict motor improvement in response to conventional physical therapy combined with functional strength training or conventional physical therapy combined with movement performance therapy. Randomized, controlled, observer-blind trial. The sample will consist of 288 participants with upper limb paresis resulting from a stroke that occurred within the previous 60 days. All will be allocated to conventional physical therapy combined with functional strength training or conventional physical therapy combined with movement performance therapy. Functional strength training and movement performance therapy will be undertaken for up to 1·5 h/day, five-days/week for six-weeks. Measurements will be undertaken before randomization, six-weeks thereafter, and six-months after stroke. Primary efficacy outcome will be the Action Research Arm Test. Explanatory measurements will include voxel-wise estimates of brain activity during hand movement, brain white matter integrity (fractional anisotropy), and brain-muscle connectivity (e.g. latency of motor evoked potentials). The primary clinical efficacy analysis will compare treatment groups using a multilevel normal linear model adjusting for stratification variables and for which therapist administered the treatment. Effect of conventional physical therapy combined with functional strength training versus conventional physical therapy combined with movement performance therapy will be summarized using the adjusted mean difference and 95% confidence interval. To identify the neural correlates of improvement in both groups, we will investigate associations between change from baseline in clinical outcomes and each explanatory measure. To identify baseline measurements that independently predict motor improvement, we will develop a multiple regression model. © 2013 The Authors. International Journal of Stroke published by John Wiley & Sons Ltd on behalf of World Stroke Organization.

Antibody Desensitization Therapy in Highly Sensitized Lung Transplant Candidates

PubMed Central

Snyder, L. D.; Gray, A. L.; Reynolds, J. M.; Arepally, G. M.; Bedoya, A.; Hartwig, M. G.; Davis, R. D.; Lopes, K. E.; Wegner, W. E.; Chen, D. F.; Palmer, S. M.

2015-01-01

As HLAs antibody detection technology has evolved, there is now detailed HLA antibody information available on prospective transplant recipients. Determining single antigen antibody specificity allows for a calculated panel reactive antibodies (cPRA) value, providing an estimate of the effective donor pool. For broadly sensitized lung transplant candidates (cPRA ≥ 80%), our center adopted a pretransplant multimodal desensitization protocol in an effort to decrease the cPRA and expand the donor pool. This desensitization protocol included plasmapheresis, solumedrol, bortezomib and rituximab given in combination over 19 days followed by intravenous immunoglobulin. Eight of 18 candidates completed therapy with the primary reasons for early discontinuation being transplant (by avoiding unacceptable antigens) or thrombocytopenia. In a mixed-model analysis, there were no significant changes in PRA or cPRA changes over time with the protocol. A sub-analysis of the median fluorescence intensity (MFI) change indicated a small decline that was significant in antibodies with MFI 5000–10 000. Nine of 18 candidates subsequently had a transplant. Posttransplant survival in these nine recipients was comparable to other pretransplant-sensitized recipients who did not receive therapy. In summary, an aggressive multi-modal desensitization protocol does not significantly reduce pretransplant HLA antibodies in a broadly sensitized lung transplant candidate cohort. PMID:24666831

A Novel Combination Therapy for Patients With Dry Eye Disease: A Pilot Study.

PubMed

Smith, Will; McMahon, David; Nymark, Maria

2018-05-01

Context • Approximately 25% of the US population suffers from dry eyes or some abnormality of the exposed ocular surface. Investigation of effective modalities for their management is needed. Objective • The study intended to examine the efficacy of a proprietary, daily, Dry Eye Protocol consisting of daily use of a moist, heated, ocular compress and intake of an omega-3 dietary supplement in treatment of ocular surface disease. Design • The research team designed a 4-wk, clinically based, open-label, multicenter cohort study. Setting • The study took place at 6 private eye care practices throughout the United States: Beverly Hills, CA, USA; San Diego, CA, USA; Sunnyvale, CA, USA; Park City, UT, USA; Tarpon Spring, FL, USA; and Kennewick, WA, USA. Participants • Participants were adults between 18 and 75 y of age who had established ocular surface disease based on clinical findings and the results of testing using the ocular surface disease index (OSDI). Intervention • For period of 30 d, participants used a combined daily protocol that included (1) application of a moist, heated, eye compress and (2) a nutritional therapy via an omega-3 supplement in an oral triglyceride form. Outcome Measures • Measures included the OSDI and a test of tear break-up time (TBUT). Results • Of the original 35 participants, 33 completed the 4-wk protocol. The participants using the proprietary Dry Eye Protocol showed significant improvements from baseline, demonstrated by a 49% decrease in OSDI scores (P = .0015); and 46% of participants reported becoming asymptomatic of dry eye symptoms. A significant improvement was also observed in TBUT, increasing from 3.0 to 5.4 s. Conclusions • Daily use of the proprietary Dry Eye Protocol that included a high dosage of triglyceride omega-3 and use of a moist, heated, compress daily showed significant improvement for participants in OSDI and TBUT and should be considered to be a first-line therapy for patients with dry eye disease.

Patient perspectives: Kundalini yoga meditation techniques for psycho-oncology and as potential therapies for cancer.

PubMed

Shannahoff-Khalsa, David S

2005-03-01

The ancient system of Kundalini Yoga (KY) includes a vast array of meditation techniques. Some were discovered to be specific for treating psychiatric disorders and others are supposedly beneficial for treating cancers. To date, 2 clinical trials have been conducted for treating obsessive-compulsive disorder (OCD). The first was an open uncontrolled trial and the second a single-blinded randomized controlled trial (RCT) comparing a KY protocol against the Relaxation Response and Mindfulness Meditation (RRMM) techniques combined. Both trials showed efficacy on all psychological scales using the KY protocol; however, the RCT showed no efficacy on any scale with the RRMM control group. The KY protocol employed an OCD-specific meditation technique combined with other techniques that are individually specific for anxiety, low energy, fear, anger, meeting mental challenges, and turning negative thoughts into positive thoughts. In addition to OCD symptoms, other symptoms, including anxiety and depression, were also significantly reduced. Elements of the KY protocol other than the OCD-specific technique also may have applications for psycho-oncology patients and are described here. Two depression-specific KY techniques are described that also help combat mental fatigue and low energy. A 7-part protocol is described that would be used in KY practice to affect the full spectrum of emotions and distress that complicate a cancer diagnosis. In addition, there are KY techniques that practitioners have used in treating cancer. These techniques have not yet been subjected to formal clinical trials but are described here as potential adjunctive therapies. A case history demonstrating rapid onset of acute relief of intense fear in a terminal breast cancer patient using a KY technique specific for fear is presented. A second case history is reported for a surviving male diagnosed in 1988 with terminal prostate cancer who has used KY therapy long term as part of a self-directed integrative care approach.

Management of orbital emphysema secondary to rhegmatogenous retinal detachment repair with hyperbaric oxygen therapy.

PubMed

Iniesta-Sanchez, Dante L; Romero-Caballero, Fatima; Aguirre-Alvarado, Adriana; Rebollo-Hurtado, Victoria; Velez-Montoya, Raul

2016-04-01

To describe the case of orbital subcutaneous emphysema who was successfully treated with hyperbaric oxygen therapy. Case report. Retrospective analysis of medical records and computer tomography images. A 40 years-old female, with retinal detachment who was seen at the emergency department, two weeks after undergoing a combined procedure of pars plana vitrectomy, scleral buckle and Sulfur hexafluoride tamponade. The patient complained of pain, decrease eye movement and edema of the upper eyelid. Clinical examination revealed periorbital crepitus. She was treated immediately with soft tissue decompression with small-gauge needle. Orbital emphysema recurred quickly, indicating possible gas trapped in the soft tissue. Using the US NAVY decompression protocol we were able to achieve fast clinical improvement. The protocol was repeated in several occasions until complete resolution. Hyperbaric oxygen therapy is an effective treatment for orbital and periorbital emphysema, due to its property of helping accelerate N 2 elimination from adipose tissue.

Modeling the effects of space structure and combination therapies on phenotypic heterogeneity and drug resistance in solid tumors.

PubMed

Lorz, Alexander; Lorenzi, Tommaso; Clairambault, Jean; Escargueil, Alexandre; Perthame, Benoît

2015-01-01

Histopathological evidence supports the idea that the emergence of phenotypic heterogeneity and resistance to cytotoxic drugs can be considered as a process of selection in tumor cell populations. In this framework, can we explain intra-tumor heterogeneity in terms of selection driven by the local cell environment? Can we overcome the emergence of resistance and favor the eradication of cancer cells by using combination therapies? Bearing these questions in mind, we develop a model describing cell dynamics inside a tumor spheroid under the effects of cytotoxic and cytostatic drugs. Cancer cells are assumed to be structured as a population by two real variables standing for space position and the expression level of a phenotype of resistance to cytotoxic drugs. The model takes explicitly into account the dynamics of resources and anticancer drugs as well as their interactions with the cell population under treatment. We analyze the effects of space structure and combination therapies on phenotypic heterogeneity and chemotherapeutic resistance. Furthermore, we study the efficacy of combined therapy protocols based on constant infusion and bang-bang delivery of cytotoxic and cytostatic drugs.

Therapeutic efficacy and toxicity of bolus application of chemotherapy protocol in the treatment of metastatic colorectal cancer.

PubMed

Šišić, Ibrahim; Pojskić, Belma; Mekić Abazović, Alma; Kovčin, Vladimir

2015-08-01

To compare efficacy and toxicity of bolus application of chemotherapy protocol, oxaliplatin, fluorouracil (bolus), leucovorin (folfox) between two groups of patients in the therapy of metastatic colorectal carcinoma (mCRC). A total of 63 patients were treated for mCRC in the period January 2009 - January 2010 at the Department of Oncology of the Cantonal Hospital Zenica, Bosnia and Herzegovina (first group, 30 patients) and at the Department of Oncology of the Clinical Hospital Centre Bežanijska kosa in Belgrade, Serbia, in the period January 2005 - January 2006 (second group, 33 patients). The patients were treated according the same protocol, i.v. bolus infusion, but in different day intervals (D), 1, 8, 15/28 days or D1-D5/28 days, respectively. In all patients the following factors were analyzed: tumor response, overall survival (OS), progression free survival, hematological and non-hematological toxicity . Colon was the primary localization in almost two thirds of patients. There was no statistically significant difference between the groups according to the age, hematological and non-hematological toxicity, as well as in achieved OS. Progression free survival expressed in months was in average 5 months though with a large range between minimal and maximal survival time. Both groups have shown equivalent efficacy to applied chemotherapy protocols. Overall survival in the two groups matched data from the literature. Further research should confirm success of the combination of chemotherapy protocols and their combination with the biological therapy. Copyright© by the Medical Assotiation of Zenica-Doboj Canton.

Combination chemotherapy increases cytotoxicity of multiple myeloma cells by modification of nuclear factor (NF)-κB activity

PubMed Central

Salem, Kelley; Brown, Charles O.; Schibler, Jeanine; Goel, Apollina

2012-01-01

The NF-κB signaling pathway is critical in myeloma cell proliferation, inhibition of apoptosis, and emergence of therapy resistance. The chemotherapeutic drugs, dexamethasone (Dex) and bortezomib (BTZ), are widely used in clinical protocols for multiple myeloma (MM) and inhibit the NF-κB signaling pathway by distinct mechanisms. This study evaluates the efficacy of combination therapy with Dex and BTZ and investigates the mechanistic underpinning of endogenous and therapy-induced NF-κB activation in MM. Human myeloma cells and bone marrow stromal cells (BMSCs) were used in monocultures and co-cultures to determine the cytotoxic effects of Dex and/or BTZ. Our results show that combined treatment of Dex with BTZ enhanced direct apoptosis of drug-sensitive and drug-resistant myeloma cells. In the presence of BMSCs, Dex plus BTZ combination inhibited ionizing radiation (IR)-induced interleukin (IL)-6 secretion from BMSCs and induced myeloma cytotoxicity. Mechanistically, Dex treatment increased IκBα protein and mRNA expression and compensated for BTZ-induced IκBα degradation. Dex plus BTZ combination inhibited basal and therapy-induced NF-κB activity with cytotoxicity in myeloma cells resistant to BTZ. Furthermore, combination therapy down-regulated the NF-κB targeted gene expression of IL-6 and manganese superoxide dismutase (MnSOD), which can induce chemo- and radio-resistance in MM. This study provides mechanistic rationale for combining the NF-κB-targeting drugs Dex and BTZ in myeloma therapy and supports potential combinations of these drugs with radiotherapy and additional chemotherapeutic drugs, for clinical benefit in MM. PMID:23063726

Combining novel technologies with improved logistics to reduce hemodialysis vascular access dysfunction.

PubMed

Roy-Chaudhury, P; Lee, T; Duncan, H; El-Khatib, M

2009-01-01

Hemodialysis (HD) vascular access dysfunction is currently a huge clinical problem for which there are no effective therapies. There are, however, a number of promising technologies that are currently at the experimental or clinical trial stage. We believe that the application of these novel technologies in combination with better clinical protocols for vascular access care could significantly reduce the current problems associated with HD vascular access.

Efficacy of monotherapies and artesunate-based combination therapies in children with uncomplicated malaria in Somalia.

PubMed

Warsame, Marian; Atta, Hoda; Klena, John D; Waqar, Butt Ahmed; Elmi, Hussein Haji; Jibril, Ali Mohamed; Hassan, Hassan Mohamed; Hassan, Abdullahi Mohamed

2009-02-01

In order to guide the antimalarial treatment policy of Somalia, we conducted therapeutic efficacy studies of routinely used antimalarial monotherapies as well as artemisinin-based combination therapies (ACTs) for uncomplicated malaria in three sentinel sites during 2003-2006. Therapeutic efficacy of chloroquine (CQ), amodiaquine (AQ) and sulfadoxine/pyrimetahmine (SP) monotherapies, and artesunate plus SP (AS+SP) or AQ (AS+AQ) were evaluated in children 6 months to 10 years old with uncomplicated malaria. For the assessment of the monotherapies, 2003 WHO protocol with 14-day follow-up was used while the 2005 WHO protocol with 28-day follow-up was used for testing the ACTs. Of the monotherapies, CQ performed very poorly with treatment failures varying from 76.5% to 88% between the sites. AQ treatment failure was low except for Janale site with treatment failure of 23.4% compared to 2.8% and 8% in Jamame and Jowhar, respectively. For SP, treatment failures from 7.8% to 12.2% were observed. A 28-day test of artemisinin-based combinations, AS+SP and AS+AQ, proved to be highly efficacious with cure rates of 98-100% supporting the choice of AS+SP combination as first line treatment for uncomplicated malaria for Somalia.

Strategies for improving the intratumoral distribution of liposomal drugs in cancer therapy

PubMed Central

Goins, Beth; Phillips, William T.; Bao, Ande

2016-01-01

Introduction A major limitation of current liposomal cancer therapies is the inability of liposome therapeutics to penetrate throughout the entire tumor mass. This inhomogeneous distribution of liposome therapeutics within the tumor has been linked to treatment failure and drug resistance. Both liposome particle transport properties and tumor microenvironment characteristics contribute to this challenge in cancer therapy. This limitation is relevant to both intravenously and intratumorally administered liposome therapeutics. Areas covered Strategies to improve the intratumoral distribution of liposome therapeutics are described. Combination therapies of intravenous liposome therapeutics with pharmacologic agents modulating abnormal tumor vasculature, interstitial fluid pressure, extracellular matrix components, and tumor associated macrophages are discussed. Combination therapies using external stimuli (hyperthermia, radiofrequency ablation, magnetic field, radiation, and ultrasound) with intravenous liposome therapeutics are discussed. Intratumoral convection-enhanced delivery (CED) of liposomal therapeutics is reviewed. Expert opinion Optimization of the combination therapies and drug delivery protocols are necessary. Further research should be conducted in appropriate cancer types with consideration of physiochemical features of liposomes and their timing sequence. More investigation of the role of tumor associated macrophages in intratumoral distribution is warranted. Intratumoral infusion of liposomes using CED is a promising approach to improve their distribution within the tumor mass. PMID:26981891

Combination Platinum-based and DNA Damage Response-targeting Cancer Therapy: Evolution and Future Directions

PubMed Central

Basourakos, Spyridon P.; Li, Likun; Aparicio, Ana M.; Corn, Paul G.; Kim, Jeri; Thompson, Timothy C.

2017-01-01

Maintenance of genomic stability is a critical determinant of cell survival and is necessary for growth and progression of malignant cells. Interstrand crosslinking (ICL) agents, including platinum-based agents, are first-line chemotherapy treatment for many solid human cancers. In malignant cells, ICL triggers the DNA damage response (DDR). When the damage burden is high and lesions cannot be repaired, malignant cells are unable to divide and ultimately undergo cell death either through mitotic catastrophe or apoptosis. The activities of ICL agents, in particular platinum-based therapies, establish a “molecular landscape,” i.e., a pattern of DNA damage that can potentially be further exploited therapeutically with DDR-targeting agents. If the molecular landscape created by platinum-based agents could be better defined at the molecular level, a systematic, mechanistic rationale(s) could be developed for the use of DDR-targeting therapies in combination/maintenance protocols for specific, clinically advanced malignancies. New therapeutic drugs such as poly(ADP-ribose) polymerase (PARP) inhibitors are examples of DDR-targeting therapies that could potentially increase the DNA damage and replication stress imposed by platinum-based agents in tumor cells and provide therapeutic benefit for patients with advanced malignancies. Recent studies have shown that the use of PARP inhibitors together with platinum-based agents is a promising therapy strategy for ovarian cancer patients with ”BRCAness”, i.e., a phenotypic characteristic of tumors that not only can involve loss-of-function mutations in either BRCA1 or BRCA2, but also encompasses the molecular features of BRCA-mutant tumors. On the basis of these promising results, additional mechanism-based studies focused on the use of various DDR-targeting therapies in combination with platinum-based agents should be considered. This review discusses, in general, (1) ICL agents, primarily platinum-based agents, that establish a molecular landscape that can be further exploited therapeutically; (2) multiple points of potential intervention after ICL agent–induced crosslinking that further predispose to cell death and can be incorporated into a systematic, therapeutic rationale for combination/maintenance therapy using DDR-targeting agents; and (3) available agents that can be considered for use in combination/maintenance clinical protocols with platinum-based agents for patients with advanced malignancies. PMID:27978798

Combination Platinum-based and DNA Damage Response-targeting Cancer Therapy: Evolution and Future Directions.

PubMed

Basourakos, Spyridon P; Li, Likun; Aparicio, Ana M; Corn, Paul G; Kim, Jeri; Thompson, Timothy C

2017-01-01

Maintenance of genomic stability is a critical determinant of cell survival and is necessary for growth and progression of malignant cells. Interstrand crosslinking (ICL) agents, including platinum-based agents, are first-line chemotherapy treatment for many solid human cancers. In malignant cells, ICL triggers the DNA damage response (DDR). When the damage burden is high and lesions cannot be repaired, malignant cells are unable to divide and ultimately undergo cell death either through mitotic catastrophe or apoptosis. The activities of ICL agents, in particular platinum-based therapies, establish a "molecular landscape," i.e., a pattern of DNA damage that can potentially be further exploited therapeutically with DDR-targeting agents. If the molecular landscape created by platinum-based agents could be better defined at the molecular level, a systematic, mechanistic rationale(s) could be developed for the use of DDR-targeting therapies in combination/maintenance protocols for specific, clinically advanced malignancies. New therapeutic drugs such as poly(ADP-ribose) polymerase (PARP) inhibitors are examples of DDR-targeting therapies that could potentially increase the DNA damage and replication stress imposed by platinum-based agents in tumor cells and provide therapeutic benefit for patients with advanced malignancies. Recent studies have shown that the use of PARP inhibitors together with platinum-based agents is a promising therapy strategy for ovarian cancer patients with "BRCAness", i.e., a phenotypic characteristic of tumors that not only can involve loss-of-function mutations in either BRCA1 or BRCA2, but also encompasses the molecular features of BRCA-mutant tumors. On the basis of these promising results, additional mechanism-based studies focused on the use of various DDR-targeting therapies in combination with platinum-based agents should be considered. This review discusses, in general, (1) ICL agents, primarily platinum-based agents, that establish a molecular landscape that can be further exploited therapeutically; (2) multiple points of potential intervention after ICL agent-induced crosslinking that further predispose to cell death and can be incorporated into a systematic, therapeutic rationale for combination/ maintenance therapy using DDR-targeting agents; and (3) available agents that can be considered for use in combination/maintenance clinical protocols with platinum-based agents for patients with advanced malignancies. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

A randomized trial of goal directed vs. standard fluid therapy in cytoreductive surgery with hyperthermic intraperitoneal chemotherapy.

PubMed

Colantonio, Luca; Claroni, Claudia; Fabrizi, Luana; Marcelli, Maria Elena; Sofra, Maria; Giannarelli, Diana; Garofalo, Alfredo; Forastiere, Ester

2015-04-01

The use of adequate fluid therapy during cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) remains controversial. The aim of the study was to assess whether the use of fluid therapy protocol combined with goal-directed therapy (GDT) is associated with a significant change in morbidity, length of hospital stay, and mortality compared to standard fluid therapy. Patients American Society of Anesthesiologists (ASA) II-III undergoing CRS and HIPEC were randomized into two groups. The GDT group (N = 38) received fluid therapy according to a protocol guided by monitored hemodynamic parameters. The control group (N = 42) received standard fluid therapy. We evaluated incidence of major complications, total length of hospital stay, total amount of fluids administered, and mortality rate. The incidence of major abdominal complications was 10.5% in GDT group and 38.1% in the control group (P = 0.005). The median duration of hospitalization was 19 days in GDT group and 29 days in the control group (P < 0.0001). The mortality rate was zero in GDT group vs. 9.5% in the control group (P = 0.12). GDT group received a significantly (P < 0.0001) lower amount of fluid (5812 ± 1244 ml) than the control group (8269 ± 1452 ml), with a significantly (P < 0.0001) lower volume of crystalloids (3884 ± 1003 vs. 68,528 ± 1413 ml). In CRS and HIPEC, the use of a GDT improves outcome in terms of incidence of major abdominal and systemic postoperative complications and length of hospital stay, compared to standard fluid therapy protocol.

Effects of virtual reality training with modified constraint-induced movement therapy on upper extremity function in acute stage stroke: a preliminary study.

PubMed

Ji, Eun-Kyu; Lee, Sang-Heon

2016-11-01

[Purpose] The purpose of this study was to investigate the effects of virtual reality training combined with modified constraint-induced movement therapy on upper extremity motor function recovery in acute stage stroke patients. [Subjects and Methods] Four acute stage stroke patients participated in the study. A multiple baseline single subject experimental design was utilized. Modified constraint-induced movement therapy was used according to the EXplaining PLastICITy after stroke protocol during baseline sessions. Virtual reality training with modified constraint-induced movement therapy was applied during treatment sessions. The Manual Function Test and the Box and Block Test were used to measure upper extremity function before every session. [Results] The subjects' upper extremity function improved during the intervention period. [Conclusion] Virtual reality training combined with modified constraint-induced movement is effective for upper extremity function recovery in acute stroke patients.

Mycobacterium tuberculosis Infection among Asian Elephants in Captivity.

PubMed

Simpson, Gary; Zimmerman, Ralph; Shashkina, Elena; Chen, Liang; Richard, Michael; Bradford, Carol M; Dragoo, Gwen A; Saiers, Rhonda L; Peloquin, Charles A; Daley, Charles L; Planet, Paul; Narachenia, Apurva; Mathema, Barun; Kreiswirth, Barry N

2017-03-01

Although awareness of tuberculosis among captive elephants is increasing, antituberculosis therapy for these animals is not standardized. We describe Mycobacterium tuberculosis transmission between captive elephants based on whole genome analysis and report a successful combination treatment. Infection control protocols and careful monitoring of treatment of captive elephants with tuberculosis are warranted.

Patients treated with orthodontic-myofunctional therapeutic protocol.

PubMed

Saccomanno, S; Antonini, G; D'Alatri, L; D'Angelantonio, M; Fiorita, A; Deli, R

2012-09-01

The aim of this study is to report three cases that needed myofunctional and orthodontic treatment and the good results achieved after the therapy. Orthodontic treatment alone, in presence of bad habits, is not enough to solve the orthodontic issues, so it needs to be combined with myofunctional treatment.

Taking Sides: An Integrative Review of the Impact of Laterality and Polarity on Efficacy of Therapeutic Transcranial Direct Current Stimulation for Anomia in Chronic Poststroke Aphasia

PubMed Central

Sandars, Margaret; Cloutman, Lauren; Woollams, Anna M.

2016-01-01

Anomia is a frequent and persistent symptom of poststroke aphasia, resulting from damage to areas of the brain involved in language production. Cortical neuroplasticity plays a significant role in language recovery following stroke and can be facilitated by behavioral speech and language therapy. Recent research suggests that complementing therapy with neurostimulation techniques may enhance functional gains, even amongst those with chronic aphasia. The current review focuses on the use of transcranial Direct Current Stimulation (tDCS) as an adjunct to naming therapy for individuals with chronic poststroke aphasia. Our survey of the literature indicates that combining therapy with anodal (excitatory) stimulation to the left hemisphere and/or cathodal (inhibitory) stimulation to the right hemisphere can increase both naming accuracy and speed when compared to the effects of therapy alone. However, the benefits of tDCS as a complement to therapy have not been yet systematically investigated with respect to site and polarity of stimulation. Recommendations for future research to help determine optimal protocols for combined therapy and tDCS are outlined. PMID:26819777

The Clinical Development of Molecularly Targeted Agents in Combination With Radiation Therapy: A Pharmaceutical Perspective

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

Ataman, Ozlem U., E-mail: ouataman@hotmail.com; Sambrook, Sally J.; Wilks, Chris

2012-11-15

Summary: This paper explores historical and current roles of pharmaceutical industry sponsorship of clinical trials testing radiation therapy combinations with molecularly targeted agents and attempts to identify potential solutions to expediting further combination studies. An analysis of clinical trials involving a combination of radiation therapy and novel cancer therapies was performed. Ongoing and completed trials were identified by searching the (clinicaltrials.gov) Web site, in the first instance, with published trials of drugs of interest identified through American Society of Clinical Oncology, European CanCer Organisation/European Society for Medical Oncology, American Society for Radiation Oncology/European Society for Therapeutic Radiology and Oncology, andmore » PubMed databases and then cross-correlated with (clinicaltrials.gov) protocols. We examined combination trials involving radiation therapy with novel agents and determined their distribution by tumor type, predominant molecular mechanisms examined in combination to date, timing of initiation of trials relative to a novel agent's primary development, and source of sponsorship of such trials. A total of 564 studies of targeted agents in combination with radiation therapy were identified with or without concomitant chemotherapy. Most studies were in phase I/II development, with only 36 trials in phase III. The tumor site most frequently studied was head and neck (26%), followed by non-small cell lung cancer. Pharmaceutical companies were the sponsors of 33% of studies overall and provided support for only 16% of phase III studies. In terms of pharmaceutical sponsorship, Genentech was the most active sponsor of radiation therapy combinations (22%), followed by AstraZeneca (14%). Most radiation therapy combination trials do not appear to be initiated until after drug approval. In phase III studies, the most common (58%) primary endpoint was overall survival. Collectively, this analysis suggests that such trials are not given priority by pharmaceutical companies. The potential reasons for this and some challenges and possible solutions are discussed.« less

Generation and customization of biosynthetic excitable tissues for electrophysiological studies and cell-based therapies.

PubMed

Nguyen, Hung X; Kirkton, Robert D; Bursac, Nenad

2018-05-01

We describe a two-stage protocol to generate electrically excitable and actively conducting cell networks with stable and customizable electrophysiological phenotypes. Using this method, we have engineered monoclonally derived excitable tissues as a robust and reproducible platform to investigate how specific ion channels and mutations affect action potential (AP) shape and conduction. In the first stage of the protocol, we combine computational modeling, site-directed mutagenesis, and electrophysiological techniques to derive optimal sets of mammalian and/or prokaryotic ion channels that produce specific AP shape and conduction characteristics. In the second stage of the protocol, selected ion channels are stably expressed in unexcitable human cells by means of viral or nonviral delivery, followed by flow cytometry or antibiotic selection to purify the desired phenotype. This protocol can be used with traditional heterologous expression systems or primary excitable cells, and application of this method to primary fibroblasts may enable an alternative approach to cardiac cell therapy. Compared with existing methods, this protocol generates a well-defined, relatively homogeneous electrophysiological phenotype of excitable cells that facilitates experimental and computational studies of AP conduction and can decrease arrhythmogenic risk upon cell transplantation. Although basic cell culture and molecular biology techniques are sufficient to generate excitable tissues using the described protocol, experience with patch-clamp techniques is required to characterize and optimize derived cell populations.

Dose calculation accuracy of different image value to density tables for cone-beam CT planning in head & neck and pelvic localizations.

PubMed

Barateau, Anaïs; Garlopeau, Christopher; Cugny, Audrey; De Figueiredo, Bénédicte Henriques; Dupin, Charles; Caron, Jérôme; Antoine, Mikaël

2015-03-01

We aimed to identify the most accurate combination of phantom and protocol for image value to density table (IVDT) on volume-modulated arc therapy (VMAT) dose calculation based on kV-Cone-beam CT imaging, for head and neck (H&N) and pelvic localizations. Three phantoms (Catphan(®)600, CIRS(®)062M (inner phantom for head and outer phantom for body), and TomoTherapy(®) "Cheese" phantom) were used to create IVDT curves of CBCT systems with two different CBCT protocols (Standard-dose Head and Standard Pelvis). Hounsfield Unit (HU) time stability and repeatability for a single On-Board-Imager (OBI) and compatibility of two distinct devices were assessed with Catphan(®)600. Images from the anthropomorphic phantom CIRS ATOM(®) for both CT and CBCT modalities were used for VMAT dose calculation from different IVDT curves. Dosimetric indices from CT and CBCT imaging were compared. IVDT curves from CBCT images were highly different depending on phantom used (up to 1000 HU for high densities) and protocol applied (up to 200 HU for high densities). HU time stability was verified over seven weeks. A maximum difference of 3% on the dose calculation indices studied was found between CT and CBCT VMAT dose calculation across the two localizations using appropriate IVDT curves. One IVDT curve per localization can be established with a bi-monthly verification of IVDT-CBCT. The IVDT-CBCTCIRS-Head phantom with the Standard-dose Head protocol was the most accurate combination for dose calculation on H&N CBCT images. For pelvic localizations, the IVDT-CBCTCheese established with the Standard Pelvis protocol provided the best accuracy. Copyright © 2015 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

A GMP-compliant protocol to expand and transfect cancer patient T cells with mRNA encoding a tumor-specific chimeric antigen receptor.

PubMed

Krug, Christian; Wiesinger, Manuel; Abken, Hinrich; Schuler-Thurner, Beatrice; Schuler, Gerold; Dörrie, Jan; Schaft, Niels

2014-10-01

Chimeric antigen receptors (CARs), which combine an antibody-derived binding domain (single chain fragment variable) with T-cell-activating signaling domains, have become a promising tool in the adoptive cellular therapy of cancer. Retro- and lenti-viral transductions are currently the standard methods to equip T cells with a CAR; permanent CAR expression, however, harbors several risks like uncontrolled auto-reactivity. Modification of T cells by electroporation with CAR-encoding RNA to achieve transient expression likely circumvents these difficulties. We here present a GMP-compliant protocol to activate and expand T cells for clinical application. The protocol is optimized in particular to produce CAR-modified T cells in clinically sufficient numbers under full GMP-compliance from late-stage cancer patients. This protocol allows the generation of 6.7 × 10(8) CAR-expressing T cells from one patient leukapheresis. The CAR-engineered T cells produced pro-inflammatory cytokines after stimulation with antigen-bearing tumor cells and lysed tumor cells in an antigen-specific manner. This functional capacity was maintained after cryopreservation. Taken together, we provide a clinically applicable protocol to transiently engineer sufficient numbers of antigen-specific patient T cells for use in adoptive cell therapy of cancer.

Preoperative immunosuppressive therapy and surgery as a treatment for anal furunculosis.

PubMed

Klein, Arnaud; Deneuche, Aymeric; Fayolle, Pascal; Hidalgo, Antoine; Scotti, Stefano; Zylberstein, Luca; Desbois, Christophe; Tessier, Dominique; Moissonnier, Pierre; Viateau, Véronique

2006-12-01

To evaluate the efficacy of combining preoperative immunosuppressive therapy with surgical excision for treatment of anal furunculosis (AF) in dogs. Retrospective study. Dogs (n=25) with stages 1-4 AF. Preoperative immunosuppressive therapy was either cyclosporine A (CyA) alone or in combination with ketoconazole (Group 1; n=18), or azathioprine combined with prednisolone (Group 2; n=7). Surgical excision of residual draining tracts, cryptectomy, and anal sacculectomy were performed. Only dogs with postoperative clinical follow-up exceeding 9 months were retained for the study. Both immunosuppressive protocols were effective in reducing progression of AF. Subsequent draining tracts excision, cryptectomy, and anal sacculectomy were bilateral (12 dogs) or unilateral (13 dogs of which 4 had bilateral anal sacculectomy). Postoperative recovery was uneventful, except for 2 dogs that had wound breakdown. Recurrence was not observed in any of the dogs that had bilateral surgical excision and or in 9 dogs that had unilateral excision. Preoperative immunosuppressive therapy, combined with bilateral surgical resection of affected tissue consistently, resulted in resolution of AF. Four dogs that had recurrence had unilateral excision despite initial bilateral involvement, suggesting that all diseased tissue should be excised. These preliminary results suggest that immunosuppressive therapy before surgical excision for AF yields minimizes recurrence in dogs.

Is there a protocol in experimental skin wounds in rats using low-level diode laser therapy (LLDLT) combining or not red and infrared wavelengths? Systematic review.

PubMed

de Lima, Fernando José Camello; de Oliveira Neto, Olavo Barbosa; Barbosa, Fabiano Timbó; do Nascimento Galvão, Ailton Mota; Ramos, Fernando Wagner Silva; de Lima, Christiane Calheiros Farias; de Sousa Rodrigues, Célio Fernando

2016-05-01

A systematic review addressing experiments with healing of skin wounds in rats using LLDLT with different active means seeking to identify a pattern in adjustments such as laser wavelength, power and fluency and analysing wound healing parameters, such as wound area, presence of fibroblasts, angiogenesis, leukocyte infiltration, epithelial coverage and antibacterial effect. It was perceived that a protocol does not exist in view of the wide variation in the use of power (9 to 500 mW) and fluency (1 to 60 J/cm2); however, between the different wavelengths, the highlight was the combined use of red and infrared wavelengths showing better results than when used alone.

Cognitive Hypnotherapy as a Transdiagnostic Protocol for Emotional Disorders.

PubMed

Alladin, Assen; Amundson, Jon

2016-01-01

This article describes cognitive hypnotherapy (CH), an integrative treatment that provides an evidence-based framework for synthesizing clinical practice and research. CH combines hypnotherapy with cognitive-behavior therapy in the management of emotional disorders. This blended version of clinical practice meets criteria for an assimilative model of integrative psychotherapy, which incorporates both theory and empirical findings. Issues related to (a) additive effect of hypnosis in treatment, (b) transdiagnostic consideration, and (c) unified treatment protocols in the treatment of emotional disorders are considered in light of cognitive hypnotherapy.

Evaluating the effectiveness of cancer drug sensitization in vitro and in vivo.

PubMed

Rytelewski, Mateusz; Buensuceso, Adrian; Leong, Hon S; Deroo, Bonnie J; Chambers, Ann F; Koropatnick, James

2015-02-06

Due to the high level of heterogeneity and mutations inherent in human cancers, single agent therapies, or combination regimens which target the same pathway, are likely to fail. Emphasis must be placed upon the inhibition of pathways that are responsible for intrinsic and/or adaptive resistance to therapy. An active field of investigation is the development and testing of DNA repair inhibitors that promote the action of, and prevent resistance to, commonly used chemotherapy and radiotherapy. We used a novel protocol to evaluate the effectiveness of BRCA2 inhibition as a means to sensitize tumor cells to the DNA damaging drug cisplatin. Tumor cell metabolism (acidification and respiration) was monitored in real-time for a period of 72 hr to delineate treatment effectiveness on a minute by minute basis. In combination, we performed an assessment of metastatic frequency using a chicken embryo chorioallantoic membrane (CAM) model of extravasation and invasion. This protocol addresses some of the weaknesses of commonly used in vitro and in vivo methods to evaluate novel cancer therapy regimens. It can be used in addition to common methods such as cell proliferation assays, cell death assays, and in vivo murine xenograft studies, to more closely discriminate amongst candidate targets and agents, and select only the most promising candidates for further development.

Prognostic significance of clinical presentation, induction and rescue treatment in 42 cases of canine centroblastic diffuse large B-cell multicentric lymphoma in the United Kingdom.

PubMed

Davies, O; Szladovits, B; Polton, G; Garden, O A; Leo, C; Lara-Garcia, A

2018-06-01

Canine lymphoma is a heterogeneous group of diseases and many previous studies have evaluated the response of a mixed population of lymphoma cases to one specific treatment protocol. The aim of this retrospective study was to describe the outcome and prognostic factors in 42 cases of multicentric centroblastic diffuse large B-cell lymphoma treated with either a COP-type (35%) or CHOP-type (64%) induction chemotherapy. The objective response rate to induction therapy was 94%; entire dogs had a greater rate of complete vs partial remissions than neutered dogs (P = .017). Median progression-free survival for the first remission (PFS1) was 182 days; absence of anaemia at diagnosis (P = .002) and pretreatment neutrophil:lymphocyte ratio (NLR) below 9.44 (P = .015) were independently predictive of longer PFS1. Fifty-eight percent of dogs received rescue protocols with an objective response rate of 81%; 31% of dogs received further rescue protocols (up to a total of 5) and the median number of protocols administered were 2. Median overall survival (OS) was 322 days, the 1-year survival rate was 38% and the 2-year survival rate was 9%. Lymphocyte:monocyte ratio above 1.43 (P = .031), NLR below 11.44 (P = .009), the combination of induction and rescue therapy (P = .030) and the total number of doxorubicin doses used (P = .002) were independently predictive of longer OS. Use of a COP-type protocol induction compared with CHOP did not undermine OS providing doxorubicin was used as rescue therapy. © 2017 John Wiley & Sons Ltd.

Effectiveness of hydroplasty and therapeutic exercise for treatment of frozen shoulder.

PubMed

Callinan, Nancy; McPherson, Scott; Cleaveland, Susan; Voss, Debra Gardiner; Rainville, Darcel; Tokar, Nancy

2003-01-01

The purpose of this retrospective review was to evaluate the effectiveness of a hydraulic distention technique (hydroplasty) combined with a therapy program for treatment of idiopathic frozen shoulder. Over a two-year period, 60 patients with idiopathic frozen shoulder were identified as having undergone the hydroplasty procedure and therapy protocol at the authors' hand center. Distention of the glenohumeral joint was achieved by an injection of a 10-mL combination of bupivacaine (Marcaine), lidocaine (Xylocaine), and corticosteroid followed by injection of 30 mL of chilled sterile normal saline. Therapy was initiated immediately after the surgeon had completed the hydroplasty. The mean active range of motion improvement was as follows: flexion 28 degrees, abduction 42 degrees, internal rotation 22 degrees, and external rotation 26 degrees. There was no significant difference in outcomes between diabetics and nondiabetics or subjects with symptoms less than six months' duration compared with subjects with symptom duration greater than six months. At discharge, only two (3%) of the subjects reported persistent pain during sleep. The hydroplasty procedure combined with a therapy program is a successful treatment for idiopathic frozen shoulder.

The integration of acetic acid iontophoresis, orthotic therapy and physical rehabilitation for chronic plantar fasciitis: a case study

PubMed Central

Costa, Ivano A; Dyson, Anita

2007-01-01

A 15-year-old female soccer player presented with chronic plantar fasciitis. She was treated with acetic acid iontophoresis and a combination of rehabilitation protocols, ultrasound, athletic taping, custom orthotics and soft tissue therapies with symptom resolution and return to full activities within a period of 6 weeks. She reported no significant return of symptoms post follow-up at 2 months. Acetic acid iontophoresis has shown promising results and further studies should be considered to determine clinical effectiveness. The combination of acetic acid iontophoresis with conservative treatments may promote recovery within a shorter duration compared to the use of one-method treatment approaches. PMID:17885679

Postsurgical Orthodontic Treatment Planning: a Case Report with 20 Years Follow-up.

PubMed

Farronato, Giampietro; Garagiola, Umberto; Carletti, Vera; Cressoni, Paolo; Mortellaro, Carmen

2011-01-01

Traditionally, maxillofacial deformities are corrected surgically after an initial orthodontic treatment phase. However in, this article, the authors emphasize the postsurgical therapeutic protocol which is extremely important for determining the final and permanent retention of the corrected occlusion. A 55 year old female with severe skeletal Class II malocclusion is presented. Combined surgical and orthodontic correction of the malocclusion was used. : The step-by-step procedure the authors followed for the postsurgical therapy is described. The goals of the postoperative therapy were to restore and rehabilitate neuromuscular function, obtain occlusal stabilization, grind teeth selectively, and final occlusion retention. The importance of a surgical occlusal splint for rehabilitating stomatognathic neuromuscular function postoperatively was demonstrated. Furthermore, the orthodontic-prosthodontic treatment ensured occlusion stability after the surgical correction. The long-term results confirmed the efficacy of the treatment protocol presented here from both functional and aesthetical perspectives. Postsurgical orthodontic treatment is an important step in the surgical and orthodontic therapy of maxillofacial deformities.

Mycobacterium tuberculosis Infection among Asian Elephants in Captivity

PubMed Central

Simpson, Gary; Zimmerman, Ralph; Shashkina, Elena; Chen, Liang; Richard, Michael; Bradford, Carol M.; Dragoo, Gwen A.; Saiers, Rhonda L.; Peloquin, Charles A.; Daley, Charles L.; Planet, Paul; Narachenia, Apurva; Mathema, Barun

2017-01-01

Although awareness of tuberculosis among captive elephants is increasing, antituberculosis therapy for these animals is not standardized. We describe Mycobacterium tuberculosis transmission between captive elephants based on whole genome analysis and report a successful combination treatment. Infection control protocols and careful monitoring of treatment of captive elephants with tuberculosis are warranted. PMID:28221115

Pilot Cases of Combined Cognitive Processing Therapy and Smoking Cessation for Smokers With Posttraumatic Stress Disorder.

PubMed

Dedert, Eric A; Resick, Patricia A; McFall, Miles E; Dennis, Paul A; Olsen, Maren; Beckham, Jean C

2016-01-01

Posttraumatic stress disorder (PTSD) and smoking are often comorbid, and both problems are in need of improved access to evidence-based treatment. The combined approach could address two high-priority problems and increase patient access to both treatments, but research is needed to determine whether this is feasible and has promise for addressing both PTSD and smoking. We collected data from 15 test cases that received a treatment combining two evidence-based treatments: cognitive processing therapy-cognitive version (CPT-C) for PTSD and integrated care for smoking cessation (ICSC). We explored two combined treatment protocols including a brief (six-session) CPT-C with five follow-up in-person sessions focused on smoking cessation (n=9) and a full 12-session CPT-C protocol with ICSC (n=6). The combined interventions were feasible and acceptable to patients with PTSD making a quit attempt. Initial positive benefits of the combined treatments were observed. The six-session dose of CPT-C and smoking cessation resulted in 6-month bioverified smoking abstinence in two of nine participants, with clinically meaningful PTSD symptom reduction in three of nine participants. In the second cohort (full CPT-C and smoking treatment), both smoking and PTSD symptoms were improved, with three of six participants abstinent from smoking and four of six participants reporting clinically meaningful reduction in PTSD symptoms. Results suggested that individuals with PTSD who smoke are willing to engage in concurrent treatment of these problems and that combined treatment is feasible. Copyright © 2015. Published by Elsevier Ltd.

Combination vinblastine, prednisolone and toceranib phosphate for treatment of grade II and III mast cell tumours in dogs.

PubMed

Olsen, Jaime A; Thomson, Maurine; O'Connell, Kathleen; Wyatt, Ken

2018-05-24

This retrospective study evaluates the progression-free interval and survival outcomes of 40 canine (Canis familiaris) patients with Patnaik grade II and III mast cell tumours treated with combination vinblastine, prednisolone and toceranib phosphate from 2011 to 2015. Patients were subdivided into three groups; patients who received neoadjuvant therapy for poorly operable lesions, patients who received adjuvant therapy following surgical resection and patients being palliated for gross metastatic disease. Median survival time (MST) for the neoadjuvant group was not reached. Median survival time for the remaining groups was 893 days and 218 days, respectively. This combination demonstrated response in 90% (26/29) patients with measurable disease. The predominant side effects related to this chemotherapy combination were gastrointestinal in origin. Further prospective studies are required to further validate the efficacy of this treatment protocol. © 2018 The Authors Veterinary Medicine and Science Published by John Wiley & Sons Ltd.

An automated voxelized dosimetry tool for radionuclide therapy based on serial quantitative SPECT/CT imaging

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

Jackson, Price A.; Kron, Tomas; Beauregard, Jean-Mathieu

2013-11-15

Purpose: To create an accurate map of the distribution of radiation dose deposition in healthy and target tissues during radionuclide therapy.Methods: Serial quantitative SPECT/CT images were acquired at 4, 24, and 72 h for 28 {sup 177}Lu-octreotate peptide receptor radionuclide therapy (PRRT) administrations in 17 patients with advanced neuroendocrine tumors. Deformable image registration was combined with an in-house programming algorithm to interpolate pharmacokinetic uptake and clearance at a voxel level. The resultant cumulated activity image series are comprised of values representing the total number of decays within each voxel's volume. For PRRT, cumulated activity was translated to absorbed dose basedmore » on Monte Carlo-determined voxel S-values at a combination of long and short ranges. These dosimetric image sets were compared for mean radiation absorbed dose to at-risk organs using a conventional MIRD protocol (OLINDA 1.1).Results: Absorbed dose values to solid organs (liver, kidneys, and spleen) were within 10% using both techniques. Dose estimates to marrow were greater using the voxelized protocol, attributed to the software incorporating crossfire effect from nearby tumor volumes.Conclusions: The technique presented offers an efficient, automated tool for PRRT dosimetry based on serial post-therapy imaging. Following retrospective analysis, this method of high-resolution dosimetry may allow physicians to prescribe activity based on required dose to tumor volume or radiation limits to healthy tissue in individual patients.« less

Synthesis of immunotargeted magneto-plasmonic nanoclusters.

PubMed

Wu, Chun-Hsien; Sokolov, Konstantin

2014-08-22

Magnetic and plasmonic properties combined in a single nanoparticle provide a synergy that is advantageous in a number of biomedical applications including contrast enhancement in novel magnetomotive imaging modalities, simultaneous capture and detection of circulating tumor cells (CTCs), and multimodal molecular imaging combined with photothermal therapy of cancer cells. These applications have stimulated significant interest in development of protocols for synthesis of magneto-plasmonic nanoparticles with optical absorbance in the near-infrared (NIR) region and a strong magnetic moment. Here, we present a novel protocol for synthesis of such hybrid nanoparticles that is based on an oil-in-water microemulsion method. The unique feature of the protocol described herein is synthesis of magneto-plasmonic nanoparticles of various sizes from primary blocks which also have magneto-plasmonic characteristics. This approach yields nanoparticles with a high density of magnetic and plasmonic functionalities which are uniformly distributed throughout the nanoparticle volume. The hybrid nanoparticles can be easily functionalized by attaching antibodies through the Fc moiety leaving the Fab portion that is responsible for antigen binding available for targeting.

Does addition of low-level laser therapy (LLLT) in conservative care of knee arthritis successfully postpone the need for joint replacement?

PubMed

Ip, David

2015-12-01

The current study evaluates whether the addition of low-level laser therapy into standard conventional physical therapy in elderly with bilateral symptomatic tri-compartmental knee arthritis can successfully postpone the need for joint replacement surgery. A prospective randomized cohort study of 100 consecutive unselected elderly patients with bilateral symptomatic knee arthritis with each knee randomized to receive either treatment protocol A consisting of conventional physical therapy or protocol B which is the same as protocol A with added low-level laser therapy. The mean follow-up was 6 years. Treatment failure was defined as breakthrough pain which necessitated joint replacement surgery. After a follow-up of 6 years, patients clearly benefited from treatment with protocol B as only one knee needed joint replacement surgery, while nine patients treated with protocol A needed surgery (p < 0.05). We conclude low-level laser therapy should be incorporated into standard conservative treatment protocol for symptomatic knee arthritis.

Outcomes of different protocols of pelvic floor physical therapy and anti-cholinergics in women with wet over-active bladder: A 4-year follow-up.

PubMed

Azuri, Joseph; Kafri, Rachel; Ziv-Baran, Tomer; Stav, Kobi

2017-03-01

We investigated the 4-year outcomes of three protocols of pelvic floor physical therapy and anticholinergic drug in women with wet over-active bladder (OAB). One hundred and sixty-four women were randomly allocated to one of four interventions: drug therapy (DT), bladder training (BT), pelvic floor muscle training (PFMT), or combined pelvic floor rehabilitation (CPFR) that includes BT, PFMT, and behavioral advice. The active treatment in each group lasted 3 months. Of the 132 women who completed a 1-year follow-up, 120 women (90%) responded to our questionnaires and therefore were included in this study. Outcome measures were the number of voids per day, number of urgency urinary incontinence (UUI) episodes per week, completely dry rate and Incontinence Quality of Life questionnaire (I-QOL) at 4 years. After 4 years of follow-up, the outcome measures improved significantly and equally in all four groups. The median number of UUI episodes/week dropped by 3, 1, 2, and 2 in the DT, BT, PFMT, and CPFR groups, respectively (P = ns). The dry rates were 25%, 31%, 44%, 34% in the DT, BT, PFMT, and CPFR groups, respectively (P = ns). I-QOL scores improved significantly in all four groups. Women who suffer from wet-OAB may experience the same degree of long-term improvement following various pelvic floor physical therapy protocols as they would from drug therapy. Neurourol. Urodynam. 36:755-758, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Boron neutron capture therapy applied to advanced breast cancers: Engineering simulation and feasibility study of the radiation treatment protocol

NASA Astrophysics Data System (ADS)

Sztejnberg Goncalves-Carralves, Manuel Leonardo

This dissertation describes a novel Boron Neutron Capture Therapy (BNCT) application for the treatment of human epidermal growth factor receptor type 2 positive (HER2+) breast cancers. The original contribution of the dissertation is the development of the engineering simulation and the feasibility study of the radiation treatment protocol for this novel combination of BNCT and HER2+ breast cancer treatment. This new concept of BNCT, representing a radiation binary targeted treatment, consists of the combination of two approaches never used in a synergism before. This combination may offer realistic hope for relapsed and/or metastasized breast cancers. This treatment assumes that the boronated anti-HER2 monoclonal antibodies (MABs) are administrated to the patient and accumulate preferentially in the tumor. Then the tumor is destroyed when is exposed to neutron irradiation. Since the use of anti-HER2 MABs yields good and promising results, the proposed concept is expected to amplify the known effect and be considered as a possible additional treatment approach to the most severe breast cancers for patients with metastasized cancer for which the current protocol is not successful and for patients refusing to have the standard treatment protocol. This dissertation makes an original contribution with an integral numerical approach and proves feasible the combination of the aforementioned therapy and disease. With these goals, the dissertation describes the theoretical analysis of the proposed concept providing an integral engineering simulation study of the treatment protocol. An extensive analysis of the potential limitations, capabilities and optimization factors are well studied using simplified models, models based on real CT patients' images, cellular models, and Monte Carlo (MCNP5/X) transport codes. One of the outcomes of the integral dosimetry assessment originally developed for the proposed treatment of advanced breast cancers is the implementation of BNCT for HER2+ breast cancers for deep seated tumors using MITRII-FCB facility with an 8 cm diameter beam (port closest-to-tumor position), with boron concentrations in the tumor higher than 32 mug/g, and for a tumor-to-healthy tissue boron concentration ratio of 8:1. The therapeutic ratios for the proposed treatment would be higher than five for skin and adipose tissue and higher than three for tumor surrounding fibroglandular tissue. The microdosimetry study shows potential improvements in the therapeutic ratios based on the expected sub-cellular boron biodistributions. The engineering simulation study of clinical cases shows the advantages of using BNCT for HER+ breast cancers. Assuming an assured high efficiency of the boron agent delivery, the proposed concept can be considered for stage IV HER2+ breast cancers in treating the metastasized tumors in brain, head and neck, and lungs.

Combined autophagy and proteasome inhibition

PubMed Central

Vogl, Dan T; Stadtmauer, Edward A; Tan, Kay-See; Heitjan, Daniel F; Davis, Lisa E; Pontiggia, Laura; Rangwala, Reshma; Piao, Shengfu; Chang, Yunyoung C; Scott, Emma C; Paul, Thomas M; Nichols, Charles W; Porter, David L; Kaplan, Janeen; Mallon, Gayle; Bradner, James E; Amaravadi, Ravi K

2014-01-01

The efficacy of proteasome inhibition for myeloma is limited by therapeutic resistance, which may be mediated by activation of the autophagy pathway as an alternative mechanism of protein degradation. Preclinical studies demonstrate that autophagy inhibition with hydroxychloroquine augments the antimyeloma efficacy of the proteasome inhibitor bortezomib. We conducted a phase I trial combining bortezomib and hydroxychloroquine for relapsed or refractory myeloma. We enrolled 25 patients, including 11 (44%) refractory to prior bortezomib. No protocol-defined dose-limiting toxicities occurred, and we identified a recommended phase 2 dose of hydroxychloroquine 600 mg twice daily with standard doses of bortezomib, at which we observed dose-related gastrointestinal toxicity and cytopenias. Of 22 patients evaluable for response, 3 (14%) had very good partial responses, 3 (14%) had minor responses, and 10 (45%) had a period of stable disease. Electron micrographs of bone marrow plasma cells collected at baseline, after a hydroxychloroquine run-in, and after combined therapy showed therapy-associated increases in autophagic vacuoles, consistent with the combined effects of increased trafficking of misfolded proteins to autophagic vacuoles and inhibition of their degradative capacity. Combined targeting of proteasomal and autophagic protein degradation using bortezomib and hydroxychloroquine is therefore feasible and a potentially useful strategy for improving outcomes in myeloma therapy. PMID:24991834

Effectiveness of Serious Games for Leap Motion on the Functionality of the Upper Limb in Parkinson's Disease: A Feasibility Study.

PubMed

Oña, Edwin Daniel; Balaguer, Carlos; Cano-de la Cuerda, Roberto; Collado-Vázquez, Susana; Jardón, Alberto

2018-01-01

The design and application of Serious Games (SG) based on the Leap Motion sensor are presented as a tool to support the rehabilitation therapies for upper limbs. Initially, the design principles and their implementation are described, focusing on improving both unilateral and bilateral manual dexterity and coordination. The design of the games has been supervised by specialized therapists. To assess the therapeutic effectiveness of the proposed system, a protocol of trials with Parkinson's patients has been defined. Evaluations of the physical condition of the participants in the study, at the beginning and at the end of the treatment, are carried out using standard tests. The specific measurements of each game give the therapist more detailed information about the patients' evolution after finishing the planned protocol. The obtained results support the fact that the set of developed video games can be combined to define different therapy protocols and that the information obtained is richer than the one obtained through current clinical metrics, serving as method of motor function assessment.

Effectiveness of Serious Games for Leap Motion on the Functionality of the Upper Limb in Parkinson's Disease: A Feasibility Study

PubMed Central

Balaguer, Carlos; Collado-Vázquez, Susana; Jardón, Alberto

2018-01-01

The design and application of Serious Games (SG) based on the Leap Motion sensor are presented as a tool to support the rehabilitation therapies for upper limbs. Initially, the design principles and their implementation are described, focusing on improving both unilateral and bilateral manual dexterity and coordination. The design of the games has been supervised by specialized therapists. To assess the therapeutic effectiveness of the proposed system, a protocol of trials with Parkinson's patients has been defined. Evaluations of the physical condition of the participants in the study, at the beginning and at the end of the treatment, are carried out using standard tests. The specific measurements of each game give the therapist more detailed information about the patients' evolution after finishing the planned protocol. The obtained results support the fact that the set of developed video games can be combined to define different therapy protocols and that the information obtained is richer than the one obtained through current clinical metrics, serving as method of motor function assessment. PMID:29849550

Cost-effectiveness of an intensive group training protocol compared to physiotherapy guideline care for sub-acute and chronic low back pain: design of a randomised controlled trial with an economic evaluation. [ISRCTN45641649

PubMed Central

van der Roer, Nicole; van Tulder, Maurits W; Barendse, Johanna M; van Mechelen, Willem; Franken, Willemien K; Ooms, Arjan C; de Vet, Henrica CW

2004-01-01

Background Low back pain is a common disorder in western industrialised countries and the type of treatments for low back pain vary considerably. Methods In a randomised controlled trial the cost-effectiveness and cost-utility of an intensive group training protocol versus physiotherapy guideline care for sub-acute and chronic low back pain patients is evaluated. Patients with back pain for longer than 6 weeks who are referred to physiotherapy care by their general practitioner or medical specialist are included in the study. The intensive group training protocol combines exercise therapy with principles of behavioural therapy ("graded activity") and back school. This training protocol is compared to physiotherapy care according to the recently published Low Back Pain Guidelines of the Royal Dutch College for Physiotherapy. Primary outcome measures are general improvement, pain intensity, functional status, work absenteeism and quality of life. The direct and indirect costs will be assessed using cost diaries. Patients will complete questionnaires at baseline and 6, 13, 26 and 52 weeks after randomisation. Discussion No trials are yet available that have evaluated the effect of an intensive group training protocol including behavioural principles and back school in a primary physiotherapy care setting and no data on cost-effectiveness and cost-utility are available. PMID:15560843

Safety of combination therapy with milrinone and esmolol for heart protection during percutaneous coronary intervention in acute myocardial infarction.

PubMed

Poh, Kian-Keong; Xu, Xin; Chan, Mark Y; Lee, Chi-Hang; Tay, Edgar L; Low, Adrian F; Chan, Koo Hui; Sia, Winnie; Tang, Liang-Qiu; Tan, Huay Cheem; Lui, Charles Y; Nguyen, Vincent; Fujise, Kenichi; Huang, Ming-He

2014-05-01

Ischemia/reperfusion injury remains an untreated clinical problem in patients with acute myocardial infarction (AMI) despite significant advances in emergent revascularization through percutaneous coronary intervention (PCI). Pharmacological intervention for infarct size reduction is unavailable. We have identified that the medications milrinone and esmolol, when administered together at the beginning of the reperfusion, significantly decrease infarct size via reducing reperfusion injury in an experimental model. The present study tested the safety of combination therapy of milrinone and esmolol (M + E) in patients with AMI. Sixteen subjects with AMI requiring PCI were consecutively recruited. M + E was intravenously infused simultaneously for 10 min started at 5 min before anticipated angioplasty balloon inflation. Another 16 consecutively recruited AMI patients requiring PCI served as a placebo arm treated per routine clinical protocol. Blood pressure (BP) and heart rate (HR) were monitored continuously during PCI. M + E combination therapy resulted in a trend of non-significant reduction in BP compared with a control group. There was a modest but significant increase in HR at the later phase of M + E infusion compared with a control group. No significant cardiac arrhythmia was induced during M + E infusion. The combination therapy with M + E produces a minimal change in hemodynamics and appears safe as an adjunctive therapy to PCI in AMI patients. Further studies are warranted.

Combined Functional Voice Therapy in Singers With Muscle Tension Dysphonia in Singing.

PubMed

Sielska-Badurek, Ewelina; Osuch-Wójcikiewicz, Ewa; Sobol, Maria; Kazanecka, Ewa; Rzepakowska, Anna; Niemczyk, Kazimierz

2017-07-01

The purpose of this study was to evaluate vocal tract function and the voice quality in singers with muscle tension dysphonia (MTD) after undergoing combined functional voice therapy of the singing voice. This is a prospective, randomized study. Forty singers (29 females and 11 males, mean age: 24.6 ± 8.8 years) with MTD were enrolled in the study. The study group consisted of 20 singers who underwent combined functional voice therapy (10-15 individual sessions, 30-40 minutes each). Singers who did not opt for vocal rehabilitation consisted of the control group. Effects of rehabilitation were assessed with videolaryngostroboscopy, palpation of the vocal tract structures, flexible fiberoptic evaluation of the pharynx and the larynx, perceptual speaking and singing voice assessment, acoustic analysis, maximal phonation time, and the Voice Handicap Index. After combined functional voice therapy in the study group, great improvement was noticed in palpation of the vocal tract structures (P < 0.001), perceptual voice assessment (P < 0.001), phonetograms (P = 0.002), and singing range obtained from acoustic analysis of glissando (P < 0.001). In the control group, no statistically significant differences were found between the first and the second assessments. Combined functional voice therapy proved to be an efficacious treatment method in singers with MTD in singing. Development of palpation and perceptual singing voice examination protocols enables one to compare results before and after rehabilitation in clinics. Copyright © 2017 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

Perianal rhabdomyosarcoma in a dog.

PubMed

Ueno, H; Kadosawa, T; Isomura, H; Okada, Y; Ochiai, K; Umemura, T; Okumura, M; Fujinaga, T

2002-05-01

A perianal rhabdomyosarcoma was diagnosed in an 11-year-old neutered male Labrador retriever. Following two incomplete surgical excisions of the tumour, the dog was treated by means of surgery combined with local radiotherapy and systemic chemotherapy using one cycle of vincristine sulphate, doxorubicin and cyclophosphamide (VAC protocol). The dog died 252 days after the first combined therapy. Radiography at this time demonstrated enlargement of the iliac lymph nodes, suggesting metastasis of the tumour. To the authors' knowledge, this is the first report of treatment of canine perianal rhabdomyosarcoma.

AD-venture program: therapeutic biking for the treatment of depression in long-term care residents with dementia.

PubMed

Buettner, Linda L; Fitzsimmons, Suzanne

2002-01-01

This project tested an innovative intervention in a controlled clinical investigation of a nonpharmacological treatment of depression in long-term care residents with dementia. This treatment utilized a wheelchair bicycle in a recreation therapy protocol, which combined small group activity therapy and one-to-one bike rides with a staff member. Depression levels were significantly reduced in the two-week portion of the study with levels maintained in the 10-week maintenance period. Improvements were also found in sleep and levels of activity engagement.

Combinational chelation therapy abrogates lead-induced neurodegeneration in rats.

PubMed

Pachauri, Vidhu; Saxena, Geetu; Mehta, Ashish; Mishra, Deepshikha; Flora, Swaran J S

2009-10-15

Lead, a ubiquitous and potent neurotoxicant causes oxidative stress which leads to numerous neurobehavioral and physiological alterations. The ability of lead to bind sulfhydryl groups or compete with calcium could be one of the reasons for its debilitating effects. In the present study, we addressed: i) if chelation therapy could circumvent the altered oxidative stress and prevent neuronal apoptosis in chronic lead-intoxicated rats, ii) whether chelation therapy could reverse biochemical and behavioral changes, and iii) if mono or combinational therapy with captopril (an antioxidant) and thiol chelating agents (DMSA/MiADMSA) is more effective than individual thiol chelator in lead-exposed rats. Results indicated that lead caused a significant increase in reactive oxygen species, nitric oxide, and intracellular free calcium levels along with altered behavioral abnormalities in locomotor activity, exploratory behavior, learning, and memory that were supported by changes in neurotransmitter levels. A fall in membrane potential, release of cytochrome c, and DNA damage indicated mitochondrial-dependent apoptosis. Most of these alterations showed significant recovery following combined therapy with captopril with MiADMSA and to a smaller extend with captopril+DMSA over monotherapy with these chelators. It could be concluded from our present results that co-administration of a potent antioxidant (like captopril) might be a better treatment protocol than monotherapy to counter lead-induced oxidative stress. The major highlight of the work is an interesting experimental evidence of the efficacy of combinational therapy using an antioxidant with a thiol chelator in reversing neurological dystrophy caused due to chronic lead exposure in rats.

Artesunate-mefloquine combination therapy in acute Plasmodium falciparum malaria in young children: a field study regarding neurological and neuropsychiatric safety.

PubMed

Frey, Sarabel G; Chelo, David; Kinkela, Mina N; Djoukoue, Florence; Tietche, Felix; Hatz, Christoph; Weber, Peter

2010-10-21

Mefloquine-artesunate combination therapy for uncomplicated falciparum malaria is one of the treatments used in African children. Data concerning neurological safety in adults and children treated with mefloquine and artesunate combination therapy is well documented in Asia. Safety data for neurological and neuropsychiatric side effects of mefloquine and artesunate combination therapy in African children are scarce, although WHO recommends this therapy in Africa. A phase IV, open label, single arm study was conducted among African children between 10 and 20 kg with acute uncomplicated falciparum malaria. They were treated over three consecutive days with a paediatric fixed-dose combination of artesunate (50 mg/d) and mefloquine (125 mg/d). Parasitological, clinical and neurological examinations and standardized questions about neuropsychiatric symptoms were carried out on days 0, 4, 7, 28 and 63. The primary objective was to assess the neurological and neuropsychiatric safety of artesunate-mefloquine combination therapy in young children. From December 2007 to March 2009, 220 children with uncomplicated Plasmodium falciparum malaria were treated with artesunate and mefloquine. 213 children were analysed according to study protocol. 50 neurological and neuropsychiatric adverse events occurred in 28 patients. Eleven drug-related neurological and neuropsychiatric adverse events occurred in eight patients. Sleeping disorders were present in 2.3%, neurological disorders in 1.4%, neuropsychiatric disorders in 1% and eating disorders in 0.5% of the patients. Adverse events were of mild to moderate intensity and resolved spontaneously. African children showed a low percentage of self-limited neurological and neuropsychiatric adverse events, confirming studies on neurological safety in Asian children treated with artesunate and mefloquine. Sleeping disorders were most frequently observed.

The role of premorbid adjustment in schizophrenia: Focus on cognitive remediation outcome.

PubMed

Buonocore, Mariachiara; Bosinelli, Francesca; Bechi, Margherita; Spangaro, Marco; Piantanida, Marco; Cocchi, Federica; Bianchi, Laura; Guglielmino, Carmelo; Mastromatteo, Antonella Rita; Cavallaro, Roberto; Bosia, Marta

2018-02-19

Premorbid adjustment has been associated with several outcomes in schizophrenia and has been proposed as an index of cognitive reserve. This study aims to comprehensively analyse the relation between premorbid adjustment and clinical, neurocognitive, socio-cognitive and functional assessments, as well as to investigate the effect of premorbid adjustment on cognitive improvements after a cognitive remediation therapy protocol. Seventy-nine clinically stabilised outpatients with schizophrenia underwent a combined intervention consisting of cognitive remediation therapy added to standard rehabilitation therapy. All patients were assessed at baseline for psychopathology, premorbid adjustment, intellectual level, cognition and functioning. Cognitive evaluations were also repeated after the intervention. At baseline, significant correlations were observed between premorbid adjustment and working memory. The global cognitive improvement after treatment was significantly predicted by age and premorbid adjustment. This study confirms the association between premorbid adjustment and cognitive impairment and is the first to highlight the possible role of premorbid adjustment on the capacity to recover from cognitive deficits through a cognitive remediation therapy protocol. The data suggest that cognitive remediation may be particularly effective for people in the early course and that the assessment of premorbid adjustment could be of value to design individualised interventions.

Comparison between consecutive and intermittent steroid pulse therapy combined with tonsillectomy for clinical remission of IgA nephropathy.

PubMed

Kamei, Daigo; Moriyama, Takahito; Takei, Takashi; Wakai, Sachiko; Nitta, Kosaku

2014-04-01

In recent years, tonsillectomy and steroid pulse (TSP) therapy have been widely performed in Japan. However, there is no consensus about the treatment protocol and indication. In this retrospective analysis, we compared patients who received tonsillectomy plus intermittent steroid pulse (SP) therapy three times in 6 months (ISP group, n = 44) with patients who received tonsillectomy plus 3 weeks of consecutive SP therapy (CSP group, n = 46) within 1 year after renal biopsy. These two different protocols were performed at two different institutions. We analyzed the clinical and histological background and clinical remission (CR), defined as disappearance of urine abnormalities at 18 months after starting treatment. Before treatment, there was no significant difference in the clinical findings except for sex between the two groups. In ISP group and CSP group, mean estimated glomerular filtration rate was 82.1 ± 20.9 and 85.9 ± 19.1 ml/min/1.73 m(2), median proteinuria was 0.55 and 0.56 g/day, and median urinary red blood cells were 20 (10-20) and 20 (6-30)/high power filed. The histological (H) grade was lower in the CSP than the ISP group (p = 0.022). The remission rate of proteinuria, hematuria, and rate of CR by the Kaplan-Meier method and logrank test were significantly higher in the CSP group than in the ISP group (CSP vs. ISP group; proteinuria: 97.8 vs. 77.3 %, p < 0.001, hematuria: 97.8 vs. 75.0 %, p = 0.005, CR: 95.6 vs. 63.6 %, p < 0.001). In the Cox proportional hazard model (forced entry), SP protocol and proteinuria before treatment were significantly associated with CR [SP protocol: hazard ratio (HR) 2.50, 95 % confidence interval (CI) 1.46-4.30, p = 0.001, proteinuria: HR 0.81, 95 % CI 0.68-0.96, p = 0.013)]. However H-grade was associated with remission of proteinuria (H-grade: hazard ratio (HR) 0.56, 95 % confidence interval (CI) 0.37-0.85, p = 0.006), and this result meant histological bias affected the remission of proteinuria. The difference of the protocol of TSP therapy may have some effect on the CR of IgAN, though the histological bias was observed in this study. The appropriate protocol and indication of TSP therapy must be analyzed and determined in the randomized controlled trial.

Use of a 660-nm Laser to Aid in the Healing of Necrotic Alveolar Mucosa Caused by Extruded Sodium Hypochlorite: A Case Report.

PubMed

Bramante, Clovis Monteiro; Duque, Jussaro Alves; Cavenago, Bruno Cavalini; Vivan, Rodrigo Ricci; Bramante, Alexandre Silva; de Andrade, Flaviana Bombarda; Duarte, Marco Antonio Hungaro

2015-11-01

The extrusion of sodium hypochlorite through the apical foramen is an accident that can occur during the flushing procedure in endodontic treatment. The symptomatology is immediate and intense, and there is a long period before the tissues return to normal. Low-level laser therapy might be useful as an adjunctive treatment for damaged soft tissues because of its anti-inflammatory and analgesic effects, which may reduce edema and prevent infection. In this clinical case, the accidental leakage of 1% sodium hypochlorite during the preparation of the root canal of a maxillary right central incisor is reported. This leakage caused immediate and intense pain and edema formation and resulted in an extensive necrotic area in the alveolar mucosa adjacent to the root of the treated tooth. The conventional treatment protocol was combined with low-level laser therapy. Clinical and radiographic examinations after 7 months revealed complete repair of the necrotic area with no paresthesia and further indicated the integrity of the apical region of the tooth where the extrusion of sodium hypochlorite occurred. The combination of low-level laser therapy with a conventional treatment protocol in this case of the extrusion of 1% sodium hypochlorite resulted in the healing of the wounds. Copyright © 2015 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

Development of a manualized protocol of massage therapy for clinical trials in osteoarthritis.

PubMed

Ali, Ather; Kahn, Janet; Rosenberger, Lisa; Perlman, Adam I

2012-10-04

Clinical trial design of manual therapies may be especially challenging as techniques are often individualized and practitioner-dependent. This paper describes our methods in creating a standardized Swedish massage protocol tailored to subjects with osteoarthritis of the knee while respectful of the individualized nature of massage therapy, as well as implementation of this protocol in two randomized clinical trials. The manualization process involved a collaborative process between methodologic and clinical experts, with the explicit goals of creating a reproducible semi-structured protocol for massage therapy, while allowing some latitude for therapists' clinical judgment and maintaining consistency with a prior pilot study. The manualized protocol addressed identical specified body regions with distinct 30- and 60-min protocols, using standard Swedish strokes. Each protocol specifies the time allocated to each body region. The manualized 30- and 60-min protocols were implemented in a dual-site 24-week randomized dose-finding trial in patients with osteoarthritis of the knee, and is currently being implemented in a three-site 52-week efficacy trial of manualized Swedish massage therapy. In the dose-finding study, therapists adhered to the protocols and significant treatment effects were demonstrated. The massage protocol was manualized, using standard techniques, and made flexible for individual practitioner and subject needs. The protocol has been applied in two randomized clinical trials. This manualized Swedish massage protocol has real-world utility and can be readily utilized both in the research and clinical settings. Clinicaltrials.gov NCT00970008 (18 August 2009).

Cost-effectiveness and cost-utility of combination therapy in early rheumatoid arthritis: randomized comparison of combined step-down prednisolone, methotrexate and sulphasalazine with sulphasalazine alone. COBRA Trial Group. Combinatietherapie Bij Reumatoïde Artritis.

PubMed

Verhoeven, A C; Bibo, J C; Boers, M; Engel, G L; van der Linden, S

1998-10-01

Assessment of the cost-effectiveness and cost-utility of early intervention in rheumatoid arthritis (RA) patients, with combined step-down prednisolone, methotrexate and sulphasalazine, compared to sulphasalazine alone. Multicentre 56 week randomized double-blind trial with full economic analysis of direct costs and utility analysis with rating scale and standard gamble measurement techniques. The combined-treatment group included 76 patients and the sulphasalazine group 78 patients. The mean total costs per patient in the first 56 weeks of follow-up were $5519 for combined treatment and $6511 for treatment with sulphasalazine alone (P = 0.37). Out-patient care, in-patient care and non-health care each contributed about one-third to the total costs. The combined-treatment group appeared to generate savings in the length of hospital stay for RA, non-protocol drugs and costs of home help, but comparisons were not statistically significant. Protocol drugs and monitoring were slightly more expensive in the combined-treatment group. Clinical, radiographic and functional outcomes significantly favoured combined treatment at week 28 (radiography also at week 56). Utility scores also favoured combined treatment. Combined treatment is cost-effective due to enhanced efficacy at lower or equal direct costs.

Retrospective analysis for treatment of naïve canine multicentric lymphoma with a 15-week, maintenance-free CHOP protocol.

PubMed

Curran, K; Thamm, D H

2016-08-01

Standard of care treatment of dogs with multicentric lymphoma includes combination chemotherapy with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP); however, owners may be hesitant to commit the resources necessary to complete a lengthy, multi-drug protocol. One hundred thirty-four client-owned dogs with multicentric lymphoma were treated with a 15-week CHOP chemotherapy protocol. The overall response rate was 98% with 104 dogs experiencing a complete response (CR). The median progression-free survival (PFS) time for all dogs was 176 days, and the median disease-specific overall survival time was 311 days. Prognostic factors identified on multivariate analysis as significant for PFS included substage, immunophenotype, hospitalization for adverse events, need for dose reduction, presence of neutrophilia at diagnosis, presence of anemia and experiencing a CR as best response to therapy. In conclusion, this protocol may be a viable alternative to CHOP protocols using a larger number of treatments. © 2015 John Wiley & Sons Ltd.

Therapeutic drug monitoring of antimetabolic cytotoxic drugs

PubMed Central

Lennard, L

1999-01-01

Therapeutic drug monitoring is not routinely used for cytotoxic agents. There are several reasons, but one major drawback is the lack of established therapeutic concentration ranges. Combination chemotherapy makes the establishment of therapeutic ranges for individual drugs difficult, the concentration-effect relationship for a single drug may not be the same as that when the drug is used in a drug combination. Pharmacokinetic optimization protocols for many classes of cytotoxic compounds exist in specialized centres, and some of these protocols are now part of large multicentre trials. Nonetheless, methotrexate is the only agent which is routinely monitored in most treatment centres. An additional factor, especially in antimetabolite therapy, is the existence of pharmacogenetic enzymes which play a major role in drug metabolism. Monitoring of therapy could include assay of phenotypic enzyme activities or genotype in addition to, or instead of, the more traditional measurement of parent drug or drug metabolites. The cytotoxic activities of mercaptopurine and fluorouracil are regulated by thiopurine methyltransferase (TPMT) and dihydropyrimidine dehydrogenase (DPD), respectively. Lack of TPMT functional activity produces life-threatening mercaptopurine myelotoxicity. Very low DPD activity reduces fluorouracil breakdown producing severe cytotoxicity. These pharmacogenetic enzymes can influence the bioavailability, pharmacokinetics, toxicity and efficacy of their substrate drugs. PMID:10190647

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

Physical Therapy Protocols for Arthroscopic Bankart Repair.

PubMed

DeFroda, Steven F; Mehta, Nabil; Owens, Brett D

Outcomes after arthroscopic Bankart repair can be highly dependent on compliance and participation in physical therapy. Additionally, there are many variations in physician-recommended physical therapy protocols. The rehabilitation protocols of academic orthopaedic surgery departments vary widely despite the presence of consensus protocols. Descriptive epidemiology study. Level 3. Web-based arthroscopic Bankart rehabilitation protocols available online from Accreditation Council for Graduate Medical Education (ACGME)-accredited orthopaedic surgery programs were included for review. Individual protocols were reviewed to evaluate for the presence or absence of recommended therapies, goals for completion of ranges of motion, functional milestones, exercise start times, and recommended time to return to sport. Thirty protocols from 27 (16.4%) total institutions were identified out of 164 eligible for review. Overall, 9 (30%) protocols recommended an initial period of strict immobilization. Variability existed between the recommended time periods for sling immobilization (mean, 4.8 ± 1.8 weeks). The types of exercises and their start dates were also inconsistent. Goals to full passive range of motion (mean, 9.2 ± 2.8 weeks) and full active range of motion (mean, 12.2 ± 2.8 weeks) were consistent with other published protocols; however, wide ranges existed within the reviewed protocols as a whole. Only 10 protocols (33.3%) included a timeline for return to sport, and only 3 (10%) gave an estimate for return to game competition. Variation also existed when compared with the American Society of Shoulder and Elbow Therapists' (ASSET) consensus protocol. Rehabilitation protocols after arthroscopic Bankart repair were found to be highly variable. They also varied with regard to published consensus protocols. This discrepancy may lead to confusion among therapists and patients. This study highlights the importance of attending surgeons being very clear and specific with regard to their physical therapy instructions to patients and therapists.

Effects of physical therapy for the management of patients with ankylosing spondylitis in the biological era.

PubMed

Giannotti, Erika; Trainito, Sabina; Arioli, Giovanni; Rucco, Vincenzo; Masiero, Stefano

2014-09-01

Exercise is considered a fundamental tool for the management of ankylosing spondylitis (AS), in combination with pharmacological therapy that with the advent of biological therapy has improved dramatically the control of signs and symptoms of this challenging disease. Current evidence shows that a specific exercise protocol has not been validated yet. The purpose of this review is to update the most recent evidence (July 2010-November 2013) about physiotherapy in AS, analyzing the possible role and synergistic interactions between exercise and biological drugs. From 117 studies initially considered, only 15 were included in the review. The results support a multimodal approach, including educational sessions, conducted in a group setting, supervised by a physiotherapist and followed by a maintaining home-based regimen. Spa exercise and McKenzie, Heckscher, and Pilates methods seem promising in AS rehabilitation, but their effectiveness should be further investigated in future randomized controlled trials (RCTs). When performed in accordance with the American College of Sports Medicine guidelines, cardiovascular training has been proven safe and effective and should be included in AS rehabilitation protocols. Exercise training plays an important role in the biological era, being now applicable to stabilized patients, leading ultimately to a better management of AS by physiatrists and rheumatologists throughout the world. On the basis of the current evidence, further research should aim to determine which exercise protocols should be recommended.

Cetuximab-induced skin exanthema: prophylactic and reactive skin therapy are equally effective.

PubMed

Wehler, Thomas C; Graf, Claudine; Möhler, Markus; Herzog, Jutta; Berger, Martin R; Gockel, Ines; Lang, Hauke; Theobald, Matthias; Galle, Peter R; Schimanski, Carl C

2013-10-01

Treatment with cetuximab is accompanied by the development of an acneiform follicular skin exanthema in more than 80 % of patients. Severe exanthema (grade III/IV) develops in about 9-19 % of patients with the necessity of cetuximab dose reduction or cessation. The study presented was a retrospective analysis of 50 gastrointestinal cancer patients treated with cetuximab in combination with either FOLFIRI or FOLFOX. One cohort of 15 patients received an in-house reactive skin protocol upon development of an exanthema. A second cohort of 15 patients received a skin prophylaxis starting with the first dose of cetuximab before clinical signs of toxicity. A third historic group of 20 patients had received no skin prophylaxis or reactive treatment. 19/20 patients of the historic group developed a skin exanthema. Grade III/IV exanthema was observed six times. Forty percent discontinued cetuximab therapy. The average time to exanthema onset was 14.7 days. Applying the reactive skin protocol after the first occurrence of an exanthema, the exanthema was downgraded as follows: No patients developed grade IV° exanthema, and two patients developed a grade II/III exanthema. In the majority of cases, the reactive skin protocol controlled the exanthema (grade 0-I°). No dose reductions in cetuximab were necessary. Applying the prophylactic skin protocol starting at the beginning of cetuximab application was not superior to the reactive skin protocol. Cetuximab-induced skin exanthema can be coped with a reactive protocol equally effective as compared to a prophylactic skin treatment. A prospective study with higher patient numbers is planned.

Combined autophagy and proteasome inhibition: a phase 1 trial of hydroxychloroquine and bortezomib in patients with relapsed/refractory myeloma.

PubMed

Vogl, Dan T; Stadtmauer, Edward A; Tan, Kay-See; Heitjan, Daniel F; Davis, Lisa E; Pontiggia, Laura; Rangwala, Reshma; Piao, Shengfu; Chang, Yunyoung C; Scott, Emma C; Paul, Thomas M; Nichols, Charles W; Porter, David L; Kaplan, Janeen; Mallon, Gayle; Bradner, James E; Amaravadi, Ravi K

2014-08-01

The efficacy of proteasome inhibition for myeloma is limited by therapeutic resistance, which may be mediated by activation of the autophagy pathway as an alternative mechanism of protein degradation. Preclinical studies demonstrate that autophagy inhibition with hydroxychloroquine augments the antimyeloma efficacy of the proteasome inhibitor bortezomib. We conducted a phase I trial combining bortezomib and hydroxychloroquine for relapsed or refractory myeloma. We enrolled 25 patients, including 11 (44%) refractory to prior bortezomib. No protocol-defined dose-limiting toxicities occurred, and we identified a recommended phase 2 dose of hydroxychloroquine 600 mg twice daily with standard doses of bortezomib, at which we observed dose-related gastrointestinal toxicity and cytopenias. Of 22 patients evaluable for response, 3 (14%) had very good partial responses, 3 (14%) had minor responses, and 10 (45%) had a period of stable disease. Electron micrographs of bone marrow plasma cells collected at baseline, after a hydroxychloroquine run-in, and after combined therapy showed therapy-associated increases in autophagic vacuoles, consistent with the combined effects of increased trafficking of misfolded proteins to autophagic vacuoles and inhibition of their degradative capacity. Combined targeting of proteasomal and autophagic protein degradation using bortezomib and hydroxychloroquine is therefore feasible and a potentially useful strategy for improving outcomes in myeloma therapy.

A pilot study of modified cognitive-behavioral therapy for childhood traumatic grief (CBT-CTG).

PubMed

Cohen, Judith A; Mannarino, Anthony P; Staron, Virginia R

2006-12-01

This pilot study evaluated outcomes for a modified 12-session protocol of cognitive-behavioral therapy for childhood traumatic grief (CBT-CTG) conducted between March 2004 and October 2005. CTG is an emerging condition characterized by a combination of posttraumatic stress and unresolved grief symptoms. This two-module treatment model consisting of sequential trauma- and grief-focused components was shortened from a previously presented 16-session protocol. Thirty-nine children ages 6 to 17 years old with CTG and their parents received the modified 12-session protocol of CBT-CTG. CTG and posttraumatic stress disorder (PTSD) symptoms were assessed at pretreatment, after the trauma-focused module, and after the grief-focused module (at posttreatment). Child depression, anxiety, and behavioral symptoms, as well as parental depression and PTSD symptoms, were assessed at pre- and posttreatment. Children reported significant improvement in CTG, PTSD, depression, and anxiety, and parents reported significant improvement in children's PTSD, internalizing and total behavior problems, and their personal PTSD symptoms. Although PTSD significantly improved only during the trauma-focused module of treatment, CTG improved significantly during both trauma- and grief-focused modules of treatment. Child satisfaction and parent satisfaction for this treatment protocol were also high. These findings suggest that the shortened CBT-CTG protocol, which is similar in the number of sessions to what many community child bereavement programs offer, may be acceptable and efficacious for this population. The CBT-CTG model requires further evaluation in randomized, controlled treatment trials.

Sequential psychological and pharmacological therapies for comorbid and primary insomnia: study protocol for a randomized controlled trial.

PubMed

Morin, Charles M; Edinger, Jack D; Krystal, Andrew D; Buysse, Daniel J; Beaulieu-Bonneau, Simon; Ivers, Hans

2016-03-03

Chronic insomnia is a prevalent disorder associated with significant psychosocial, health, and economic impacts. Cognitive behavioral therapies (CBTs) and benzodiazepine receptor agonist (BzRA) medications are the most widely supported therapeutic approaches for insomnia management. However, few investigations have directly compared their relative and combined benefits, and even fewer have tested the benefits of sequential treatment for those who do not respond to initial insomnia therapy. Moreover, insomnia treatment studies have been limited by small, highly screened study samples, fixed-dose, and fixed-agent pharmacotherapy strategies that do not represent usual clinical practices. This study will address these limitations. This is a two-site randomized controlled trial, which will enroll 224 adults who meet the criteria for a chronic insomnia disorder with or without comorbid psychiatric disorders. Prospective participants will complete clinical assessments and polysomnography and then will be randomly assigned to first-stage therapy involving either behavioral therapy (BT) or zolpidem. Treatment outcomes will be assessed after 6 weeks, and treatment remitters will be followed for the next 12 months on maintenance therapy. Those not achieving remission will be offered randomization to a second, 6-week treatment, again involving either pharmacotherapy (zolpidem or trazodone) or psychological therapy (BT or cognitive therapy (CT)). All participants will be re-evaluated 12 weeks after the protocol initiation and at 3-, 6-, 9-, and 12-month follow-ups. Insomnia remission, defined categorically as a score < 8 on the Insomnia Severity Index, a patient-reported outcome, will serve as the primary endpoint for treatment comparisons. Secondary outcomes will include sleep parameters derived from daily sleep diaries and from polysomnography, subjective measures of fatigue, mood, quality of life, and functional impairments; and measures of adverse events; dropout rates; and treatment acceptability. Centrally trained therapists will administer therapies according to manualized, albeit flexible, treatment algorithms. This clinical trial will provide new information about optimal treatment sequencing and will have direct implication for the development of clinical guidelines for managing chronic insomnia with and without comorbid psychiatric conditions. ClinicalTrials.gov Identifier: NCT01651442 , Protocol version 4, 20 April 2011, registered 26 June 2012.

A systematic review of postoperative hand therapy management of basal joint arthritis.

PubMed

Wolfe, Terri; Chu, Jennifer Y; Woods, Tammy; Lubahn, John D

2014-04-01

There are a variety of postoperative immobilization and therapy options for patients with basal joint arthritis. Although prior systematic reviews have compared surgical procedures used to treat basal joint arthritis, none to our knowledge compares therapy protocols for this condition, which are considered an important part of the treatment. (1) We sought to determine whether differences in the length and type of postoperative immobilization affect clinical results after basal joint arthritis surgery. (2) We also compared specific therapy protocols that were prescribed. (3) Finally, we evaluated published protocols to determine when patients were released to full activity to see whether these appeared to affect clinical results. A systematic review of English-language studies in the PubMed and Cochrane databases was performed. Studies were then reviewed to determine what postoperative immobilization and therapy protocols the authors used and when patients were released to full activities. A total of 19 studies were identified using the search criteria. All but one of the studies included a postoperative period of immobilization in either a cast or splint. Immobilization time varied depending on whether Kirschner wires were used for the surgery and whether an implant was placed. Postoperative therapy protocols also varied but followed three general patterns. Some therapy protocols involved teaching patients a home exercise program only, whereas some authors described routine referral to a therapist. The third group consisted of studies in which patients were only referred for therapy if the physicians determined it was necessary during followup. Many studies did not give a specific time for full return to activity and instead described a gradual transition to full activity after immobilization was discontinued. Because of the variability and small numbers, no conclusive recommendations could be made on any of the three study questions. Comparative, multicenter studies comparing different immobilization and therapy protocols after the surgical treatment of basal joint arthritis would be helpful for both surgeons and therapists looking to refine their treatment protocols.

Synthesis of Immunotargeted Magneto-plasmonic Nanoclusters

PubMed Central

Wu, Chun-Hsien; Sokolov, Konstantin

2014-01-01

Magnetic and plasmonic properties combined in a single nanoparticle provide a synergy that is advantageous in a number of biomedical applications including contrast enhancement in novel magnetomotive imaging modalities, simultaneous capture and detection of circulating tumor cells (CTCs), and multimodal molecular imaging combined with photothermal therapy of cancer cells. These applications have stimulated significant interest in development of protocols for synthesis of magneto-plasmonic nanoparticles with optical absorbance in the near-infrared (NIR) region and a strong magnetic moment. Here, we present a novel protocol for synthesis of such hybrid nanoparticles that is based on an oil-in-water microemulsion method. The unique feature of the protocol described herein is synthesis of magneto-plasmonic nanoparticles of various sizes from primary blocks which also have magneto-plasmonic characteristics. This approach yields nanoparticles with a high density of magnetic and plasmonic functionalities which are uniformly distributed throughout the nanoparticle volume. The hybrid nanoparticles can be easily functionalized by attaching antibodies through the Fc moiety leaving the Fab portion that is responsible for antigen binding available for targeting. PMID:25177973

Exploratory clinical trial of combination wound therapy with a gelatin sheet and platelet-rich plasma in patients with chronic skin ulcers: study protocol.

PubMed

Morimoto, Naoki; Kakudo, Natsuko; Matsui, Makoto; Ogura, Tsunetaka; Hara, Tomoya; Suzuki, Kenji; Yamamoto, Masaya; Tabata, Yasuhiko; Kusumoto, Kenji

2015-05-11

Chronic skin ulcers, such as diabetic ulcers, venous leg ulcers and pressure ulcers, are intractable and increasing in prevalence, representing a costly problem in healthcare. We developed a combination therapy with a gelatin sheet, capable of providing sustained release of platelet-rich plasma (PRP). The objective of this study is to investigate the safety and efficacy of autologous PRP covered with a hydrocolloid dressing and PRP covered with a gelatin sheet in the treatment of chronic skin ulcers. Thirty patients with chronic skin ulcers who have not healed with conventional therapy for at least 1 month are being recruited. The patients will receive PRP after debridement, and the wounds will be covered with a hydrocolloid dressing or gelatin sheet. The efficacy will be evaluated according to the time from the beginning of PRP application to secondary healing or the day on which wound closure is achieved with a relatively simple surgical procedure, such as skin grafting or suturing. All patients will be followed up until 6 weeks after application to observe adverse events related to the application of PRP and the dressings. This study was designed to address and compare the safety and efficacy of PRP covered with a hydrocolloid dressing versus a gelatin sheet. If successful, this combination therapy may be an alternative to bioengineered skin substitutes containing living cells and lead to substantial progress in the management of chronic skin ulcers. The study protocol was approved by the Institutional Review Board of Kansai Medical University (KMU Number 0649-1, 4 August 2014: V.1.0). The findings of this trial will be disseminated through peer-reviewed journals, and national and international scientific meetings as well as to the patients. UMIN000015689. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

[Magnetic resonance imaging of brain tumors].

PubMed

Prayer, Daniela; Brugger, P C

2002-01-01

Investigating intracranial tumors, different MR-related methods permit not only morphological visualization of lesions but also give insights into their metabolism, resulting in information about the biological qualities of the respective tumor. Magnetic resonance protocols are selected based on the type and timing of onset of clinical signs. Combined information from imaging studies and spectroscopy facilitates the differential diagnosis between blastomatous and non-blastomatous lesions before and after therapy.

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

Association between post-game recovery protocols, physical and perceived recovery, and performance in elite Australian Football League players.

PubMed

Bahnert, Andrew; Norton, Kevin; Lock, Phillip

2013-03-01

To determine the associations between post-game recovery protocols and physical and perceptual recovery, and game performance in Australian Football League players. A longitudinal quasi-experimental study design was used across a season. A full squad of 44 footballers was monitored weekly across a 23-game season. Players were required to choose from a number of recovery modalities available immediately post-game. These included floor stretching, pool stretching, bike active recovery, pool active recovery, cold-water immersion, contrast therapy and use of a compression garment. Perceptual measures of recovery were recorded throughout the week and a test of physical performance was conducted two days post-game. Game performance ratings were also recorded. The associations between the post-game recovery protocols chosen and players' perceived recovery, and physical and game performances were determined by the association rule data-mining strategy. Statistically significant associations were found between a number of post-game recovery protocols and perceptual recovery. In general, players who chose cold-water immersion, floor stretching, no active recovery (neither bike or pool) and the use of a compression garment post-game, had an increased probability of reporting greater perceptual recovery across the following week, relative to all other permutations of recovery protocols chosen. There were no associations found between post-game recovery protocol combinations and physical recovery. No associations were found between the post-game recovery methods and the next game performance. Perceptual recovery among players was enhanced through the selection of specific combinations of recovery protocols post game. However, no links were found between recovery protocols and physical or game performance measures. Copyright © 2012 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

Efficacy of a protocol including heparin ointment for treatment of multikinase inhibitor-induced hand-foot skin reactions.

PubMed

Li, Jian-ri; Yang, Chi-rei; Cheng, Chen-li; Ho, Hao-chung; Chiu, Kun-yuan; Su, Chung-Kuang; Chen, Wen-Ming; Wang, Shian-Shiang; Chen, Chuan-Shu; Yang, Cheng-Kuang; Ou, Yen-chuan

2013-03-01

The purpose of this study is to evaluate the efficacy of a protocol including topical heparin therapy for hand-foot skin reactions (HFSR) during multikinase (MKI) treatment. We prospectively collected 26 patients who had HFSRs during treatment with the MKIs, sunitinib, sorafenib, or axitinib. The age distribution ranged from 46 to 87 years, with a mean of 66 years. The distribution of HFSR severity was 12 patients with grade 1, 12 with grade 2, and 2 with grade 3. A heparin-containing topical ointment treatment, combined with hand-foot shock absorbers and skin moisturizers, was used at the lesion sites. Changes in the grade of HFSR, MKI dosage, and interruptions of MKI therapy were recorded. The results showed that 66.7% of grade 1 patients were cured of disease, 83.3% of grade 2 patients had improved symptoms, and both grade 3 patients (100%) had improved symptoms and were downgraded to grade 2. Four (15.4%) patients required reduction of MKI dosage, but there were no treatment interruptions or dropouts. Our protocol is beneficial in promoting resolution of HFSRs induced by MKIs. Further validation in large control studies should be investigated.

Systems oncology: towards patient-specific treatment regimes informed by multiscale mathematical modelling.

PubMed

Powathil, Gibin G; Swat, Maciej; Chaplain, Mark A J

2015-02-01

The multiscale complexity of cancer as a disease necessitates a corresponding multiscale modelling approach to produce truly predictive mathematical models capable of improving existing treatment protocols. To capture all the dynamics of solid tumour growth and its progression, mathematical modellers need to couple biological processes occurring at various spatial and temporal scales (from genes to tissues). Because effectiveness of cancer therapy is considerably affected by intracellular and extracellular heterogeneities as well as by the dynamical changes in the tissue microenvironment, any model attempt to optimise existing protocols must consider these factors ultimately leading to improved multimodal treatment regimes. By improving existing and building new mathematical models of cancer, modellers can play important role in preventing the use of potentially sub-optimal treatment combinations. In this paper, we analyse a multiscale computational mathematical model for cancer growth and spread, incorporating the multiple effects of radiation therapy and chemotherapy in the patient survival probability and implement the model using two different cell based modelling techniques. We show that the insights provided by such multiscale modelling approaches can ultimately help in designing optimal patient-specific multi-modality treatment protocols that may increase patients quality of life. Copyright © 2014 Elsevier Ltd. All rights reserved.

Comparison of 10 efficient protocols for photodynamic therapy of actinic keratosis: How relevant are effective light dose and local damage in predicting the complete response rate at 3 months?

PubMed

Vignion-Dewalle, Anne-Sophie; Baert, Gregory; Thecua, Elise; Lecomte, Fabienne; Vicentini, Claire; Abi-Rached, Henry; Mortier, Laurent; Mordon, Serge

2018-04-18

Topical photodynamic therapy is an established treatment modality for various dermatological conditions, including actinic keratosis. In Europe, the approved protocols for photodynamic therapy of actinic keratosis involve irradiation with either an Aktilite CL 128 lamp or daylight, whereas irradiation with the Blu-U illuminator is approved in the United States. Many other protocols using irradiation by a variety of light sources are also clinically efficient. This paper aims to compare 10 different protocols with clinically proven efficacy for photodynamic therapy of actinic keratosis and the available spectral irradiance of the light source. Effective irradiance, effective light dose, and local damage are compared. We also investigate whether there is an association between the complete response rate at 3 months and the effective light dose or local damage. The effective irradiance, also referred to as protoporphyrin IX-weighted irradiance, is obtained by integrating the spectral irradiance weighted by the normalized absorption spectrum of protoporphyrin IX over the wavelength. Integrating the effective irradiance over the irradiation time yields the effective light dose, which is also known as the protoporphyrin IX-weighted light dose. Local damage, defined as the total cumulative singlet oxygen molecules produced during treatment, is estimated using mathematical modeling of the photodynamic therapy process. This modeling is based on an iterative procedure taking into account the spatial and temporal variations in the protoporphyrin IX absorption spectrum during treatment. The protocol for daylight photodynamic therapy on a clear sunny day, the protocol for daylight photodynamic therapy on an overcast day, the photodynamic therapy protocol for a white LED lamp for operating rooms and the photodynamic therapy protocol for the Blu-U illuminator perform better than the six other protocols-all involving red light illumination-in terms of both effective light dose and local damage. However, no association between the complete response rate at 3 months and the effective light dose or local damage was found. Protocols that achieve high complete response rates at 3 months and low pain scores should be preferred regardless of the effective light dose and local damage. Lasers Surg. Med. © 2018 Wiley Periodicals, Inc. © 2018 Wiley Periodicals, Inc.

[MRI and prostate cancer: a paradigm shift].

PubMed

Lemaitre, L; Rouvière, O; Penna-Renard, R; Villers, A; Puech, P

2008-09-01

A shift in the use of prostate MR for diagnosis, staging, and pre-treatment planning over the last several years has modified the MR protocols. Classically used to detect extra-prostatic tumor, MR now plays a role for diagnosis (pre-biopsy evaluation in a patient with elevated PSA and suspected cancer in an unusual site), treatment planning (prostate mapping), and follow-up after treatment (evaluation for local recurrence or follow-up after HIFU, radiation therapy, or focal treatment...). Imaging protocols at 1.5T and 3.0T combine morphological T2W imaging with functional sequences (perfusion imaging, diffusion imaging, spectroscopy) using high-resolution phased array pelvic coils or "combined" coils (added endorectal coil). To promote acceptance by clinicians and increased access to patients, the indications for prostate MR must be better defined (and provide useful data to urologists), the cost must be reduced, and results must be more reproducible and standardized.

Protocol for HER2 FISH Using a Non-cross-linking, Formalin-free Tissue Fixative to Combine Advantages of Cryo-preservation and Formalin Fixation

PubMed Central

Loibner, Martina; Oberauner-Wappis, Lisa; Viertler, Christian; Groelz, Daniel; Zatloukal, Kurt

2017-01-01

Morphologic assessment of formalin-fixed, paraffin-embedded (FFPE) tissue samples has been the gold standard for cancer diagnostics for decades due to its excellent preservation of morphology. Personalized medicine increasingly provides individually adapted and targeted therapies for characterized individual diseases enabled by combined morphological and molecular analytical technologies and diagnostics. Performance of morphologic and molecular assays from the same FFPE specimen is challenging because of the negative impact of formalin due to chemical modification and cross-linking of nucleic acids and proteins. A non-cross-linking, formalin-free tissue fixative has been recently developed to fulfil both requirements, i.e., to preserve morphology like FFPE and biomolecules like cryo-preservation. Since FISH is often required in combination with histopathology and molecular diagnostics, we tested the applicability of FISH protocols on tissues treated with this new fixative. We found that formalin post-fixation of histological sections of non-cross-linking, formalin-free and paraffin-embedded (NCFPE) breast cancer tissue generated equivalent results to those with FFPE tissue in human epidermal growth factor receptor 2 (HER2) FISH analysis. This protocol describes how a FISH assay originally developed and validated for FFPE tissue can be used for NCFPE tissues by a simple post-fixation step of histological sections. PMID:29364207

Coping-Infused Dialogue through Patient-Preferred Live Music: A Medical Music Therapy Protocol and Randomized Pilot Study for Hospitalized Organ Transplant Patients.

PubMed

Hogan, Tyler James; Silverman, Michael J

2015-01-01

Solid organ transplant patients often experience a variety of psychosocial stressors that can lead to distress and may hinder successful recovery. Using coping-infused dialogue (CID) through patient- preferred live music (PPLM) music therapy sessions may improve mood and decrease pain while also imparting psychoeducational knowledge concerning the identification of local and global problems and coping skills. The purpose of this pilot study was to develop a coping-based medical music therapy protocol that combines coping-infused dialogue (CID) with patient-preferred live music (PPLM) and measure the effects of the resulting CID-PPLM protocol on mood (positive and negative affect) and pain in hospitalized transplant patients. Our study used a pre-/posttest single-session wait-list control design. Participants (N=25) were randomly assigned to experimental (CID-PPLM) or control (usual care) conditions. Participants in the CID-PPLM condition received a single 30-minute session that integrated stressor identification and knowledge of coping skills (CID) with patient-preferred live music (PPLM). Results indicated no between-group differences at pretest and significant correlations between pre- and posttest measures. Concerning posttest ANCOVA analyses, there were significant between-group differences in positive affect, negative affect, and pain, with experimental participants having more favorable posttest scores than control participants. Effect sizes were in the medium-to-large range for positive affect (η2=.198), negative affect (η2=.422), and pain (η2=.303). CID through receptive PPLM may be an effective protocol for improving mood and decreasing pain in organ transplant recipients. MT interventions can be an important tool to develop rapport and enhance outcomes with patients. As greater engagement during interventions may have stronger treatment effects, we recommend future research examining patient engagement as a potential mediator of intervention effects, as well as the number of sessions required to maximize clinical outcomes. © the American Music Therapy Association 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Treatment of patients with multiple myeloma over 65 yr: more tolerability or better response?

PubMed

Tarkun, Pinar; Atalay, Figen; Atesoglu, Elif Birtas; Mehtap, Ozgur; Simsek, Melih; Terzi, Esra; Geduk, Ayfer; Balli, Fatih; Batman, Adnan; Baydemir, Canan; Hacihanefioglu, Abdullah

2015-05-01

Two-thirds of newly diagnosed patients with multiple myeloma (MM) are over 65 yr and/or physically unfit. Such patients are not eligible for high-dose chemotherapy or stem cell transplantation. The treatment aims in these patients should be to prolong survival by obtaining the best possible response, while maintaining good tolerability. The aim of our study was to evaluate the response to treatment and treatment-related toxicities in patients treated with conventional and novel protocols. The records of 138 elderly (≥65 yr) patients with MM were retrospectively evaluated. The median overall survival(OS) of the patients was 46 months. The median progression-free survival (PFS) was 18 months. The OS and PFS of the patients treated with the conventional protocols did not differ significantly from those treated with the novel protocols. The statistical analysis of the quality of the response to the treatment with the conventional and novel therapies showed that complete remission (CR), combined with a very good partial response (VGPR), was significantly higher in the latter. However, the toxicities were higher in the novel treatment group. The novel drug protocols significantly increased the quality of the responses of elderly patients with MM to therapy, but they did not increase the patients' tolerability. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Gene therapy for adenosine deaminase-deficient severe combined immune deficiency: clinical comparison of retroviral vectors and treatment plans.

PubMed

Candotti, Fabio; Shaw, Kit L; Muul, Linda; Carbonaro, Denise; Sokolic, Robert; Choi, Christopher; Schurman, Shepherd H; Garabedian, Elizabeth; Kesserwan, Chimene; Jagadeesh, G Jayashree; Fu, Pei-Yu; Gschweng, Eric; Cooper, Aaron; Tisdale, John F; Weinberg, Kenneth I; Crooks, Gay M; Kapoor, Neena; Shah, Ami; Abdel-Azim, Hisham; Yu, Xiao-Jin; Smogorzewska, Monika; Wayne, Alan S; Rosenblatt, Howard M; Davis, Carla M; Hanson, Celine; Rishi, Radha G; Wang, Xiaoyan; Gjertson, David; Yang, Otto O; Balamurugan, Arumugam; Bauer, Gerhard; Ireland, Joanna A; Engel, Barbara C; Podsakoff, Gregory M; Hershfield, Michael S; Blaese, R Michael; Parkman, Robertson; Kohn, Donald B

2012-11-01

We conducted a gene therapy trial in 10 patients with adenosine deaminase (ADA)-deficient severe combined immunodeficiency using 2 slightly different retroviral vectors for the transduction of patients' bone marrow CD34(+) cells. Four subjects were treated without pretransplantation cytoreduction and remained on ADA enzyme-replacement therapy (ERT) throughout the procedure. Only transient (months), low-level (< 0.01%) gene marking was observed in PBMCs of 2 older subjects (15 and 20 years of age), whereas some gene marking of PBMC has persisted for the past 9 years in 2 younger subjects (4 and 6 years). Six additional subjects were treated using the same gene transfer protocol, but after withdrawal of ERT and administration of low-dose busulfan (65-90 mg/m(2)). Three of these remain well, off ERT (5, 4, and 3 years postprocedure), with gene marking in PBMC of 1%-10%, and ADA enzyme expression in PBMC near or in the normal range. Two subjects were restarted on ERT because of poor gene marking and immune recovery, and one had a subsequent allogeneic hematopoietic stem cell transplantation. These studies directly demonstrate the importance of providing nonmyeloablative pretransplantation conditioning to achieve therapeutic benefits with gene therapy for ADA-deficient severe combined immunodeficiency.

Gene therapy for adenosine deaminase–deficient severe combined immune deficiency: clinical comparison of retroviral vectors and treatment plans

PubMed Central

Candotti, Fabio; Shaw, Kit L.; Muul, Linda; Carbonaro, Denise; Sokolic, Robert; Choi, Christopher; Schurman, Shepherd H.; Garabedian, Elizabeth; Kesserwan, Chimene; Jagadeesh, G. Jayashree; Fu, Pei-Yu; Gschweng, Eric; Cooper, Aaron; Tisdale, John F.; Weinberg, Kenneth I.; Crooks, Gay M.; Kapoor, Neena; Shah, Ami; Abdel-Azim, Hisham; Yu, Xiao-Jin; Smogorzewska, Monika; Wayne, Alan S.; Rosenblatt, Howard M.; Davis, Carla M.; Hanson, Celine; Rishi, Radha G.; Wang, Xiaoyan; Gjertson, David; Yang, Otto O.; Balamurugan, Arumugam; Bauer, Gerhard; Ireland, Joanna A.; Engel, Barbara C.; Podsakoff, Gregory M.; Hershfield, Michael S.; Blaese, R. Michael; Parkman, Robertson

2012-01-01

We conducted a gene therapy trial in 10 patients with adenosine deaminase (ADA)–deficient severe combined immunodeficiency using 2 slightly different retroviral vectors for the transduction of patients' bone marrow CD34+ cells. Four subjects were treated without pretransplantation cytoreduction and remained on ADA enzyme-replacement therapy (ERT) throughout the procedure. Only transient (months), low-level (< 0.01%) gene marking was observed in PBMCs of 2 older subjects (15 and 20 years of age), whereas some gene marking of PBMC has persisted for the past 9 years in 2 younger subjects (4 and 6 years). Six additional subjects were treated using the same gene transfer protocol, but after withdrawal of ERT and administration of low-dose busulfan (65-90 mg/m2). Three of these remain well, off ERT (5, 4, and 3 years postprocedure), with gene marking in PBMC of 1%-10%, and ADA enzyme expression in PBMC near or in the normal range. Two subjects were restarted on ERT because of poor gene marking and immune recovery, and one had a subsequent allogeneic hematopoietic stem cell transplantation. These studies directly demonstrate the importance of providing nonmyeloablative pretransplantation conditioning to achieve therapeutic benefits with gene therapy for ADA-deficient severe combined immunodeficiency. PMID:22968453

Trabectedin therapy as an emerging treatment strategy for recurrent platinum-sensitive ovarian cancer.

PubMed

López-Guerrero, José Antonio; Romero, Ignacio; Poveda, Andrés

2015-01-01

Epithelial ovarian cancer (OC) is a common gynecologic malignancy in women. The standard treatment for OC is maximal cytoreductive surgical debulking followed by platinum-based chemotherapy. Despite the high response rate to primary therapy, approximately 85% of patients will develop recurrent ovarian cancer (ROC). This review identifies the clinical use of trabectedin in the treatment algorithm for ROC, with specific emphasis on platinum-sensitive ROC, for which trabectedin in combination with pegylated liposomal doxorubicin has been approved as a treatment protocol. The main mechanisms of action of trabectedin at the cellular level and in the tumor microenvironment is also discussed as bases for identifying biomarkers for selecting patients who may largely benefit from trabectedin-based therapies.

Daptomycin plus fosfomycin versus daptomycin monotherapy in treating MRSA: protocol of a multicentre, randomised, phase III trial.

PubMed

Shaw, E; Miró, J M; Puig-Asensio, M; Pigrau, C; Barcenilla, F; Murillas, J; Garcia-Pardo, G; Espejo, E; Padilla, B; Garcia-Reyne, A; Pasquau, J; Rodriguez-Baño, J; López-Contreras, J; Montero, M; de la Calle, C; Pintado, V; Calbo, E; Gasch, O; Montejo, M; Salavert, M; Garcia-Pais, M J; Carratalà, J; Pujol, M

2015-03-11

Despite the availability of new antibiotics such as daptomycin, methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia continues to be associated with high clinical failure rates. Combination therapy has been proposed as an alternative to improve outcomes but there is a lack of clinical studies. The study aims to demonstrate that combination of daptomycin plus fosfomycin achieves higher clinical success rates in the treatment of MRSA bacteraemia than daptomycin alone. A multicentre open-label, randomised phase III study. Adult patients hospitalised with MRSA bacteraemia will be randomly assigned (1:1) to group 1: daptomycin 10 mg/kg/24 h intravenous; or group 2: daptomycin 10 mg/kg/24 h intravenous plus fosfomycin 2 gr/6 g intravenous. The main outcome will be treatment response at week 6 after stopping therapy (test-of-cure (TOC) visit). This is a composite variable with two values: Treatment success: resolution of clinical signs and symptoms (clinical success) and negative blood cultures (microbiological success) at the TOC visit. Treatment failure: if any of the following conditions apply: (1) lack of clinical improvement at 72 h or more after starting therapy; (2) persistent bacteraemia (positive blood cultures on day 7); (3) therapy is discontinued early due to adverse effects or for some other reason based on clinical judgement; (4) relapse of MRSA bacteraemia before the TOC visit; (5) death for any reason before the TOC visit. Assuming a 60% cure rate with daptomycin and a 20% difference in cure rates between the two groups, 103 patients will be needed for each group (α:0.05, ß: 0.2). Statistical analysis will be based on intention to treat, as well as per protocol and safety analysis. The protocol was approved by the Spanish Medicines and Healthcare Products Regulatory Agency (AEMPS). The sponsor commits itself to publishing the data in first quartile peer-review journals within 12 months of the completion of the study. NCT01898338. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

A Phase 1/2 Trial of a Combination of Paclitaxel and Trastuzumab With Daily Irradiation or Paclitaxel Alone With Daily Irradiation After Transurethral Surgery for Noncystectomy Candidates With Muscle-Invasive Bladder Cancer (Trial NRG Oncology RTOG 0524)

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

Michaelson, M. Dror, E-mail: dmichaelson1@partners.org; Hu, Chen; Sydney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland

Purpose: Bladder preservation therapy is an effective treatment for muscle-invasive urothelial carcinoma (UC). In this study we treated noncystectomy candidates with daily radiation and weekly paclitaxel for 7 weeks. Patients whose tumors showed her2/neu overexpression were additionally treated with weekly trastuzumab. Methods and Materials: Sixty-eight evaluable patients were treated with radiation therapy and either paclitaxel + trastuzumab (group 1) or paclitaxel alone (group 2). Groups were assigned on the basis of her2/neu immunohistochemistry results. Patients received 1.8-Gy fractions to a total dose of 64.8 Gy. The primary endpoint of the study was treatment-related toxicity, and secondary endpoints included complete response (CR) rate, protocol completionmore » rate, and survival. Results: A total of 20 evaluable patients were treated in group 1 and 46 patients in group 2. Acute treatment-related adverse events (AEs) were observed in 7 of 20 patients in group 1 (35%) and 14 of 46 patients in group 2 (30.4%). Protocol therapy was completed by 60% (group 1) and 74% (group 2) of patients. Most incompletions were due to toxicity, and the majority of AEs were gastrointestinal, including 1 grade 5 AE (group 1). Two other deaths (both in group 2) were unrelated to protocol therapy. No unexpected cardiac, hematologic, or other toxicities were observed. The CR rate at 1 year was 72% for group 1 and 68% for group 2. Conclusions: In patients with muscle-invasive UC who are not candidates for cystectomy, daily radiation combined with paclitaxel is an effective treatment strategy with a high completion rate and moderate toxicity. In patients with her2/neu-positive tumors, a group generally considered to have worse outcomes, the addition of trastuzumab appears to result in comparable efficacy and toxicity. Further biomarker-driven trials should be undertaken in advancing treatment of this challenging disease.« less

BODY-ORIENTED THERAPY IN RECOVERY FROM CHILD SEXUAL ABUSE: AN EFFICACY STUDY

PubMed Central

Price, Cynthia

2007-01-01

Context There has been little research on body therapy for women in sexual abuse recovery. This study examines body-oriented therapy—an approach focused on body awareness and involving the combination of bodywork and the emotional processing of psychotherapy. Objective To examine the efficacy and the perceived influence on abuse recovery of body-oriented therapy. Massage therapy served as a relative control condition to address the lack of touch-based comparisons in bodywork research. Design A 2-group, repeated measures design was employed, involving randomization to either body-oriented therapy or massage group, conducted in 8, hour-long sessions by 1 of 4 research clinicians. Statistical and qualitative analysis was employed to provide both empirical and experiential perspectives on the study process. Setting Participants were seen in treatment rooms of a university in the northwestern United States and in clinician’s private offices. Participants Twenty-four adult females in psychotherapy for child sexual abuse. Interventions Body-oriented therapy protocol was delivered in three stages, involving massage, body awareness exercises, and inner-body focusing process. Massage therapy protocol was stan- dardized. Both protocols were delivered over clothes. Main Outcome Measures The outcomes reflected 3 key con-structs—psychological well being, physical well-being, and body connection. Repeated measures included: Brief Symptom Inventory, Dissociative Experiences Scale, Crime-Related Post Traumatic Stress Disorder Scale, Medical Symptoms Checklist, Scale of Body Connection and Scale of Body Investment. Results were gathered at 6 time points: baseline, 2 times during intervention, post-intervention, and at 1 month and 3 months follow-up. To examine the experiential perspective of the study process, written questionnaires were administered before and after intervention and at 1 month and 3 months follow-up. Results Repeated measures analysis of variance (ANOVA) indicated significant improvement on all outcome measures for both intervention groups, providing support for the efficacy of body therapy in recovery from childhood sexual abuse. There were no statistically significant differences between groups; however, qualitative analysis of open-ended questions about participant intervention experience revealed that the groups differed on perceived experience of the intervention and its influence on therapeutic recovery. PMID:16189948

Meaning and challenges in the practice of multiple therapeutic massage modalities: a combined methods study.

PubMed

Porcino, Antony J; Boon, Heather S; Page, Stacey A; Verhoef, Marja J

2011-09-20

Therapeutic massage and bodywork (TMB) practitioners are predominantly trained in programs that are not uniformly standardized, and in variable combinations of therapies. To date no studies have explored this variability in training and how this affects clinical practice. Combined methods, consisting of a quantitative, population-based survey and qualitative interviews with practitioners trained in multiple therapies, were used to explore the training and practice of TMB practitioners in Alberta, Canada. Of the 5242 distributed surveys, 791 were returned (15.1%). Practitioners were predominantly female (91.7%), worked in a range of environments, primarily private (44.4%) and home clinics (35.4%), and were not significantly different from other surveyed massage therapist populations. Seventy-seven distinct TMB therapies were identified. Most practitioners were trained in two or more therapies (94.4%), with a median of 8 and range of 40 therapies. Training programs varied widely in number and type of TMB components, training length, or both. Nineteen interviews were conducted. Participants described highly variable training backgrounds, resulting in practitioners learning unique combinations of therapy techniques. All practitioners reported providing individualized patient treatment based on a responsive feedback process throughout practice that they described as being critical to appropriately address the needs of patients. They also felt that research treatment protocols were different from clinical practice because researchers do not usually sufficiently acknowledge the individualized nature of TMB care provision. The training received, the number of therapies trained in, and the practice descriptors of TMB practitioners are all highly variable. In addition, clinical experience and continuing education may further alter or enhance treatment techniques. Practitioners individualize each patient's treatment through a highly adaptive process. Therefore, treatment provision is likely unique to each practitioner. These results may be of interest to researchers considering similar practice issues in other professions. The use of a combined-methods design effectively captured this complexity of TMB practice. TMB research needs to consider research approaches that can capture or adapt to the individualized nature of practice.

THE MASTER PROTOCOL CONCEPT

PubMed Central

Allegra, Carmen J.

2015-01-01

During the past decade, biomedical technologies have undergone an explosive evolution---from the publication of the first complete human genome in 2003, after more than a decade of effort and at a cost of hundreds of millions of dollars---to the present time, where a complete genomic sequence can be available in less than a day and at a small fraction of the cost of the original sequence. The widespread availability of next generation genomic sequencing has opened the door to the development of precision oncology. The need to test multiple new targeted agents both alone and in combination with other targeted therapies, as well as classic cytotoxic agents, demand the development of novel therapeutic platforms (particularly Master Protocols) capable of efficiently and effectively testing multiple targeted agents or targeted therapeutic strategies in relatively small patient subpopulations. Here, we describe the Master Protocol concept, with a focus on the expected gains and complexities of the use of this design. An overview of Master Protocols currently active or in development is provided along with a more extensive discussion of the Lung Master Protocol (Lung-MAP study). PMID:26433553

Positive imagery cognitive bias modification (CBM) and internet-based cognitive behavioural therapy (iCBT) versus control CBM and iCBT for depression: study protocol for a parallel-group randomised controlled trial.

PubMed

Williams, Alishia D; Blackwell, Simon E; Holmes, Emily A; Andrews, Gavin

2013-10-29

The current randomised controlled trial will evaluate the efficacy of an internet-delivered positive imagery cognitive bias modification (CBM) intervention for depression when compared with an active control condition and help establish the additive benefit of positive imagery CBM when delivered in combination with internet cognitive behavioural therapy for depression. Patients meeting diagnostic criteria for a current major depressive episode will be recruited through the research arm of a not-for-profit clinical and research unit in Australia. The minimum sample size for each group (α set at 0.05, power at 0.80) was identified as 29, but at least 10% more will be recruited to hedge against expected attrition. We will measure the impact of CBM on primary measures of depressive symptoms (Beck Depression Inventory-second edition (BDI-II), Patient Health Questionnaire (PHQ9)) and interpretive bias (ambiguous scenarios test-depression), and on a secondary measure of psychological distress (Kessler-10 (K10)) following the 1-week CBM intervention. Secondary outcome measures of psychological distress (K10), as well as disability (WHO disability assessment schedule-II), repetitive negative thinking (repetitive thinking questionnaire), and anxiety (state trait anxiety inventory-trait version) will be evaluated following completion of the 11-week combined intervention, in addition to the BDI-II and PHQ9. Intent-to-treat marginal and mixed effect models using restricted maximum likelihood estimation will be used to evaluate the primary hypotheses. Clinically significant change will be defined as high-end state functioning (a BDI-II score <14) combined with a total score reduction greater than the reliable change index score. Maintenance of gains will be assessed at 3-month follow-up. The current trial protocol has been approved by the Human Research Ethics Committee of St Vincent's Hospital and the University of New South Wales, Sydney. Australian New Zealand Clinical Trials Registry: ACTRN12613000139774 and Clinicaltrials.gov: NCT01787513. This trial protocol is written in compliance with the Standard Protocol Items: recommendations for Interventional Trials (SPIRIT) guidelines.

Targeting oncomiRNAs and mimicking tumor suppressor miRNAs: New trends in the development of miRNA therapeutic strategies in oncology (Review)

PubMed Central

GAMBARI, ROBERTO; BROGNARA, ELEONORA; SPANDIDOS, DEMETRIOS A.; FABBRI, ENRICA

2016-01-01

MicroRNA (miRNA or miR) therapeutics in cancer are based on targeting or mimicking miRNAs involved in cancer onset, progression, angiogenesis, epithelial-mesenchymal transition and metastasis. Several studies conclusively have demonstrated that miRNAs are deeply involved in tumor onset and progression, either behaving as tumor-promoting miRNAs (oncomiRNAs and metastamiRNAs) or as tumor suppressor miRNAs. This review focuses on the most promising examples potentially leading to the development of anticancer, miRNA-based therapeutic protocols. The inhibition of miRNA activity can be readily achieved by the use of miRNA inhibitors and oligomers, including RNA, DNA and DNA analogues (miRNA antisense therapy), small molecule inhibitors, miRNA sponges or through miRNA masking. On the contrary, the enhancement of miRNA function (miRNA replacement therapy) can be achieved by the use of modified miRNA mimetics, such as plasmid or lentiviral vectors carrying miRNA sequences. Combination strategies have been recently developed based on the observation that i) the combined administration of different antagomiR molecules induces greater antitumor effects and ii) some anti-miR molecules can sensitize drug-resistant tumor cell lines to therapeutic drugs. In this review, we discuss two additional issues: i) the combination of miRNA replacement therapy with drug administration and ii) the combination of antagomiR and miRNA replacement therapy. One of the solid results emerging from different independent studies is that miRNA replacement therapy can enhance the antitumor effects of the antitumor drugs. The second important conclusion of the reviewed studies is that the combination of anti-miRNA and miRNA replacement strategies may lead to excellent results, in terms of antitumor effects. PMID:27175518

An overview of interstitial brachytherapy and hyperthermia

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

Brandt, B.B.; Harney, J.

Interstitial thermoradiotherapy, an experimental cancer treatment that combines interstitial radiation implants (brachytherapy) and interstitial hyperthermia, is in the early stages of investigation. In accordance with the procedure used in a current national trial protocol, a 60-minute hyperthermia treatment is administered after catheters are placed into the tumor area while the patient is under general anesthesia. This is immediately followed by loading of radioactive Iridium-192 seeds into the catheters for a defined period of time. Once the prescribed radiation dose is delivered, the radioactive sources are removed and a second, 60-minute hyperthermia treatment is administered. Clinical trials with hyperthermia in combinationmore » with radiation have increased in recent years. Nurses caring for these patients need to become more knowledgeable about this investigational therapy. This paper provides an overview of the biologic rationale for this therapy, as well as a description of the delivery method and clinical application. Specific related nursing interventions are defined in a nursing protocol.23 references.« less

Feasibility and safety of early combined cognitive and physical therapy for critically ill medical and surgical patients: the Activity and Cognitive Therapy in ICU (ACT-ICU) trial.

PubMed

Brummel, N E; Girard, T D; Ely, E W; Pandharipande, P P; Morandi, A; Hughes, C G; Graves, A J; Shintani, A; Murphy, E; Work, B; Pun, B T; Boehm, L; Gill, T M; Dittus, R S; Jackson, J C

2014-03-01

Cognitive impairment after critical illness is common and debilitating. We developed a cognitive therapy program for critically ill patients and assessed the feasibility and safety of administering combined cognitive and physical therapy early during a critical illness. We randomized 87 medical and surgical ICU patients with respiratory failure and/or shock in a 1:1:2 manner to three groups: usual care, early once-daily physical therapy, or early once-daily physical therapy plus a novel, progressive, twice-daily cognitive therapy protocol. Cognitive therapy included orientation, memory, attention, and problem-solving exercises, and other activities. We assessed feasibility outcomes of the early cognitive plus physical therapy intervention. At 3 months, we also assessed cognitive, functional, and health-related quality of life outcomes. Data are presented as median (interquartile range) or frequency (%). Early cognitive therapy was a delivered to 41/43 (95%) of cognitive plus physical therapy patients on 100% (92-100%) of study days beginning 1.0 (1.0-1.0) day following enrollment. Physical therapy was received by 17/22 (77%) of usual care patients, by 21/22 (95%) of physical therapy only patients, and 42/43 (98%) of cognitive plus physical therapy patients on 17% (10-26%), 67% (46-87%), and 75% (59-88%) of study days, respectively. Cognitive, functional, and health-related quality of life outcomes did not differ between groups at 3-month follow-up. This pilot study demonstrates that early rehabilitation can be extended beyond physical therapy to include cognitive therapy. Future work to determine optimal patient selection, intensity of treatment, and benefits of cognitive therapy in the critically ill is needed.

Feasibility and safety of early combined cognitive and physical therapy for critically ill medical and surgical patients: the Activity and Cognitive Therapy in ICU (ACT-ICU) trial

PubMed Central

Brummel, N.E.; Girard, T.D.; Ely, E.W.; Pandharipande, P.P.; Morandi, A.; Hughes, C.G.; Graves, A.J.; Shintani, A.K.; Murphy, E.; Work, B.; Pun, B.T.; Boehm, L.; Gill, T.M.; Dittus, R.S.; Jackson, J.C.

2013-01-01

PURPOSE Cognitive impairment after critical illness is common and debilitating. We developed a cognitive therapy program for critically ill patients and assessed the feasibility and safety of administering combined cognitive and physical therapy early during a critical illness. METHODS We randomized 87 medical and surgical ICU patients with respiratory failure and/or shock in a 1:1:2 manner to three groups: usual care, early once-daily physical therapy, or early once-daily physical therapy plus a novel, progressive, twice-daily cognitive therapy protocol. Cognitive therapy included orientation, memory, attention, and problem solving exercises, and other activities. We assessed feasibility outcomes of the early cognitive plus physical therapy intervention. At 3-months, we also assessed cognitive, functional and health-related quality of life outcomes. Data are presented as median [interquartile range] or frequency (%). RESULTS Early cognitive therapy was a delivered to 41/43 (95%) of cognitive plus physical therapy patients on 100% [92–100%] of study days beginning 1.0 [1.0–1.0] day following enrollment. Physical therapy was received by 17/22 (77%) of usual care patients, by 21/22 (95%) of physical therapy only patients and 42/43 (98%) of cognitive plus physical therapy patients on 17% [10–26%], 67% [46–87%] and 75% [59–88%] of study days, respectively. Cognitive, functional and health-related quality of life outcomes did not differ between groups at 3-month follow-up. CONCLUSIONS This pilot study demonstrates that early rehabilitation can be extended beyond physical therapy to include cognitive therapy. Future work to determine optimal patient selection, intensity of treatment and benefits of cognitive therapy in the critically ill is needed. PMID:24257969

Effectiveness of comprehensive fixed appliance treatment used with the Forsus Fatigue Resistant Device in Class II patients.

PubMed

Franchi, Lorenzo; Alvetro, Lisa; Giuntini, Veronica; Masucci, Caterina; Defraia, Efisio; Baccetti, Tiziano

2011-07-01

To assess the dental, skeletal, and soft tissue effects of comprehensive fixed appliance treatment combined with the Forsus Fatigue Resistant Device (FRD) in Class II patients. Thirty-two Class II patients (mean age 12.7 ± 1.2 years) were treated consecutively with the FRD protocol and compared with a matched sample of 27 untreated Class II subjects (mean age 12.8 ± 1.3 years). Lateral cephalograms were taken before therapy and at the completion of comprehensive therapy. The mean duration of comprehensive treatment was 2.4 ± 0.4 years. Statistical comparisons were carried out with the Student's t-test (P < .05). The success rate was 87.5%. The FRD group showed a significant restraint in the sagittal skeletal position of the maxilla (also at the soft tissue level), a significant increase in mandibular length, and a significant improvement in maxillo-mandibular sagittal skeletal relationships. The treated group exhibited a significant reduction in overjet and a significant increase in molar relationship. The lower incisors were significantly proclined and intruded, while the lower first molars moved significantly in a mesial and vertical direction. The FRD protocol is effective in correcting Class II malocclusion with a combination of skeletal (mainly maxillary) and dentoalveolar (mainly mandibular) modifications.

Variability and Comprehensiveness of North American Online Available Physical Therapy Protocols Following Hip Arthroscopy for Femoroacetabular Impingement and Labral Repair.

PubMed

Cvetanovich, Gregory L; Lizzio, Vincent; Meta, Fabien; Chan, Derek; Zaltz, Ira; Nho, Shane J; Makhni, Eric C

2017-11-01

To assess comprehensiveness and variability of postoperative physical therapy protocols published online following hip arthroscopy for femoroacetabular impingement (FAI) and/or labral repair. Surgeons were identified by the International Society for Hip Arthroscopy "Find a Surgeon" feature in North America (http://www.isha.net/members/, search August 10, 2016). Exclusion criteria included nonsurgeons and protocols for conditions other than hip arthroscopy for FAI and/or labral tear. Protocols were identified by review of surgeons' personal and departmental websites and evaluated for postoperative restrictions, rehabilitation components, and the time points for ending restrictions and initiating activities. Of 111 surgeons available online, 31 (27.9%) had postoperative hip arthroscopy physical therapy protocols available online. Bracing was used in 54.8% (17/31) of protocols for median 2-week duration (range, 1-6 weeks). Most protocols specified the initial postoperative weight-bearing status (29/31, 93.5%), most frequently partial weight-bearing with 20 pounds foot flat (20/29, 69.0%). The duration of weight-bearing restriction was median 3 weeks (range, 2-6) for FAI and median 6 weeks (range, 3-8) for microfracture. The majority of protocols specified initial range of motion limitations (26/31, 83.9%) for median 3 weeks (range, 1.5-12). There was substantial variation in the rehabilitation activities and time points for initiating activities. Time to return to running was specified by 20/31 (64.5%) protocols at median 12 weeks (range, 6-19), and return to sport timing was specified by 13/31 (41.9%) protocols at median 15.5 weeks (range, 9-23). There is considerable variability in postoperative physical therapy protocols available online following hip arthroscopy for FAI, including postoperative restrictions, rehabilitation activities, and time points for activities. This information offers residents, fellows, and established hip arthroscopists a centralized comparison of publicly available physical therapy protocols following hip arthroscopy. Practicing arthroscopists might find this analysis useful to compare various therapy strategies to their own recommendations. The variability we report can also provide inspiration for future efficacy research toward a more standard rehabilitation. Copyright © 2017. Published by Elsevier Inc.

Management of complicated shunt infections: a clinical report.

PubMed

James, Hector E; Bradley, John S

2008-03-01

The authors present their experience with a protocol for the treatment of patients with complicated shunt infections. Complicated shunt infections are defined for the purpose of this protocol as multiple compartment hydrocephalus, multiple organism shunt infection, severe peritonitis, or infections in other sites of the body. The initial treatment protocol for these patients was 3 weeks of intravenous antibiotic therapy and 2 weeks of twice daily intraventricular/intrashunt antibiotic therapy. Cerebrospinal fluid (CSF) cultures were monitored during therapy and obtained again 48 hours after completion. The shunt was completely replaced. Additionally, follow-up cultures were obtained in all patients 3-6 months after therapy was completed. A cure of the infection was achieved in all patients as defined by negative cultures obtained at completion of antibiotic therapy and in follow-up studies. The follow-up period was 2-11 years (mean 4.4 +/- 2.5 years). The treatment protocol was modified in the patients treated after 1991, and 18 patients were treated with this modified treatment regime. In these patients, intraventricular antibiotics were administered only once daily for 14 days, and the CSF was cultured 24 hours after antibiotic therapy had been stopped instead of after 48 hours. The results were similar to those obtained with the initial protocol. Based on their prospective nonrandomized series, the authors believe that patients with complicated shunt infections can be successfully treated with 2 weeks of intraventricular antibiotic therapy administered once daily, concurrent with 3 weeks of intravenous antibiotic therapy. This protocol reduces length of treatment and hospital stay, and avoids recurrence of infection.

Current and long-term technologies of laser therapy

NASA Astrophysics Data System (ADS)

Ulashcyk, Vladimir S.; Volotovskaya, Anna V.

2007-06-01

Laser therapy, using low-energy laser radiation, is being more and more applied. The most applied technology is transcutaneous radiation of tissues by laser radiation. Originally, a direct action on a pathological site was mostly used, but recently more attention is given to reflexogenic areas, acupuncture points, and endocrine organ projection sites. The development of light-conductive engineering made it possible to practically apply intraorgan laser therapy. This technology is widely spread in gynecology, otorhinolaryngology, urology, gastroenterology, etc. Close to it are different versions of intratissue laser therapy (intraosteal, periosteal, myofascial). A special kind of laser therapy is laser hemotherapy. Depending on the techniques and protocol of its application, there are extracorporeal, intravascular, and supravenous ways of action. According to our comparative investigations, supravenous hemotherapy by its therapeutic efficacy and major medicinal effects can be well compared with intravascular laser hemotherapy. With good prospects and efficiency is laser therapy as a combination of laser and other physical factors. Magnetolaser therapy has been scientifically substantiated and practically applied so far. Theoretically and experimentally substantiated is a combined application of laser radiation and physical factors such as ultrasound, direct current field, vacuum, cryotherapy, etc. Experimental research and few so far clinical observations are indicative of prospects of a complex application of laser radiation and drugs. To improve light absorption, laser radiation is combined with different dyes. Photodynamic therapy, originally used in oncology, is applied today in treating different diseases. We showed a possibility of using a number of drugs possessing simultaneously photosensitizing properties to this end. Laser radiation significantly influences pharmacokinetics and pharmacodynamics of drugs, which gives reason to practically implement laser technologies, based on pharmacomodulating action of laser radiation, to practical medicine.

Extracorporeal shockwave therapy versus exercise program in patients with low back pain: short-term results of a randomised controlled trial.

PubMed

Notarnicola, A; Maccagnano, G; Gallone, M F; Mastromauro, L; Rifino, F; Pesce, V; Covelli, I; Moretti, B

2018-01-01

The physiotherapy treatment of low back pain (LBP) with physical stimulation offers different possibilities of application. Until now, the physical therapies used in LBP are laser therapy, ultrasonotherapy and currents. We conducted a clinical trial in order to verify whether shockwave therapy, which is very effective in treating tendinopathies and fracture consolidation delays, leads to clinical and electromyographic improvement in patients affected by LBP. We randomized thirty patients affected by LBP treated with shock waves (shockwave group) or a standard protocol characterized by rehabilitative exercises (control group). At one and three months, the patients treated with shockwave therapy showed clinical improvement measured by VAS scales (p=0.002; p= 0.02), and disability evaluated with Roland scales (p=0.002; p=0.002) and Oswestry (p=0.002; p=0.002). At three months, the patients treated with shock waves, showed a significant improvement in terms of values of amplitude of the sensory nerve conduction velocity (SNCV) of the plantar medialis nerve (left: p=0.007; right: p=0.04), the motor nerve muscular conduction (MNCV) of the deep peroneal nerve (left: p=0.28; right: p=0.01) and recruitment of motor units of finger brevis extensor (left: p = 0.02; right: p=0.006). In the control group, there was a trend to increase the clinical and electromyographic results without statistical significance. The preliminary results suggest a good applicability of shockwave therapy in the treatment of LBP, in accordance with the antiinflammatory, antalgic, decontracting effects and remodeling of the nerve fiber damage verified in previous studies conducted on other pathological models. Future research will allow us to verify the integration of this therapy into a rehabilitation protocol combined with other physical therapies.

Combination therapy including serratiopeptidase improves outcomes of mechanical-antibiotic treatment of periimplantitis.

PubMed

Sannino, G; Gigola, P; Puttini, M; Pera, F; Passariello, C

2013-01-01

This study was designed as a retrospective analysis of clinical outcomes of cases of periimplantitis treated by mechanical debridement and the administration of antibiotics combined or not with the administration of either the proteolytic enzyme serratiopeptidase (SPEP) or non-steroidal anti-inflammatory drugs (NSAIDs). Clinical charts of 544 partially edentulous patients treated for periimplantitis between June 1996 and December 2010 were analyzed to obtain clinical data of the affected implants just before the beginning of treatment and 12 months later to evaluate the outcomes of combined mechanical antibiotic treatment alone or in combination with the co-administration of the anti-inflammatory SPEP or NSAIDs. The comparative analysis revealed that therapeutic outcomes were significantly different in the three groups. Failure rate in the group that received SPEP (6 percent) was significantly lower compared to the group that received NSAIDS (16.9 percent; P less than 0.01) and to the group that received no anti-inflammatory therapy (18.9 percent; P less than 0.01). Treatment including SPEP was associated with significantly better healing also when successful treatments alone were considered. The data reported in this paper strongly support the hypothesis that SPEP is a valid addition to protocols for the combined therapy of peri-implantitis. In fact, it allows to enhance success rates significantly and also favors better tissue repair around successfully treated implants as compared to other regimens.

Pressurized intraperitoneal aerosol chemotheprapy after misdiagnosed gastric cancer: Case report and review of the literature.

PubMed

Nowacki, Maciej; Grzanka, Dariusz; Zegarski, Wojciech

2018-05-21

We report the first application of pressurized intraperitoneal aerosol chemotherapy (PIPAC) as a rescue therapy before palliative D2 gastrectomy combined with liver metastasectomy performed in a 49-year-old woman with peritoneal carcinomatosis who was primarily diagnosed with and underwent surgery for a Krukenberg tumor. The PIPAC procedure was performed with the use of cisplatin at 7.5 mg/m 2 and doxorubicin at 1.5 mg/m 2 for 30 min at 37 °C. Eight weeks after the PIPAC procedure, the patient underwent open classic D2 gastrectomy with the creation of a Roux-en-Y anastomosis (RNY) combined with liver metastasectomy. The patient underwent the classic protocol for chemotherapy combined with Xeloda. The patient felt better and returned to her daily activities. Multicenter data should be gathered to confirm the usefulness of PIPAC as a rescue or neoadjuvant supportive therapy in a very select group of patients who have been recently qualified to undergo classic chemotherapy or standard oncologic surgical procedures.

Combined occlusal and pharmacological therapy in the treatment of temporo-mandibular disorders.

PubMed

Inchingolo, F; Tatullo, M; Marrelli, M; Inchingolo, A M; Tarullo, A; Inchingolo, A D; Dipalma, G; Podo Brunetti, S; Tarullo, A; Cagiano, R

2011-11-01

Aim of the present work is to assess the effectiveness of a scientific protocol built up to relieve pain in chronic temporo-mandibular disorders (TMD) using Michigan splint together with a pharmacological therapy compared to the traditional occlusal therapy by Michigan splint alone. 35 adult patients, with signs and symptoms of TMD lasting more than 6 months, were enrolled into this study and divided into two groups: the first receiving occlusal therapy by Michigan splint and pharmacological therapy with Delorazepam and Thiocolchicoside, while the second receiving occlusal therapy by Michigan splint and "placebo" administration. The comparisons between the two experimental groups were assessed using a 5 steps visual-analogue scale (V.A.S.). The outcomes from the experimental groups were statistically compared resulting significantly different with an improvement or disappearance of signs and symptoms in the treated group with respect to the placebo group at 12 and 18 months from the beginning of the experiment (p < 0.001).

Management of cardiovascular risk factors with pioglitazone combination therapies in type 2 diabetes: an observational cohort study

PubMed Central

2011-01-01

Background Type 2 diabetes (T2D) is strongly associated with cardiovascular risk and requires medications that improve glycemic control and other cardiovascular risk factors. The authors aimed to assess the relative effectiveness of pioglitazone (Pio), metformin (Met) and any sulfonylurea (SU) combinations in non-insulin-treated T2D patients who were failing previous hypoglycemic therapy. Methods Over a 1-year period, two multicenter, open-labeled, controlled, 1-year, prospective, observational studies evaluated patients with T2D (n = 4585) from routine clinical practice in Spain and Greece with the same protocol. Patients were eligible if they had been prescribed Pio + SU, Pio + Met or SU + Met serving as a control cohort, once they had failed with previous therapy. Anthropometric measurements, lipid and glycemic profiles, blood pressure, and the proportions of patients at microvascular and macrovascular risk were assessed. Results All study treatment combinations rendered progressive 6-month and 12-month lipid, glycemic, and blood pressure improvements. Pio combinations, especially Pio + Met, were associated with increases in HDL-cholesterol and decreases in triglycerides and in the atherogenic index of plasma. The proportion of patients at high risk decreased after 12 months in all study cohorts. Minor weight changes (gain or loss) and no treatment-related fractures occurred during the study. The safety profile was good and proved similar among treatments, except for more hypoglycemic episodes in patients receiving SU and for the occurrence of edema in patients using Pio combinations. Serious cardiovascular events were rarely reported. Conclusions In patients with T2D failing prior hypoglycemic therapies, Pio combinations with SU or Met (especially Pio + Met) improved blood lipid and glycemic profiles, decreasing the proportion of patients with a high microvascular or macrovascular risk. The combination of Pio with SU or Met may therefore be recommended for T2D second-line therapy in the routine clinical practice, particularly in patients with dyslipidemia. PMID:21314919

Efficacy of rasagiline for the treatment of Parkinson's disease: an updated meta-analysis.

PubMed

Chang, Ying; Wang, Li-Bo; Li, Dan; Lei, Ke; Liu, Song-Yan

2017-08-01

Rasagiline is a second-generation potent selective inhibitor of monoamine oxidase-B. The aim of the study was to analyze the effectiveness of rasagiline in treatment of Parkinson's disease (PD), both as monotherapy and combination therapy. Medline, Cochrane, EMBASE, and Google Scholar databases were searched until 9 March 2016 using the keywords: Rasagiline, Azilect, Parkinson's disease. Randomized controlled trials of patients with PD who were randomized to treatment with rasagiline or placebo were included. Outcomes were unified Parkinson's disease rating scale (UPDRS) and the three subscales. Ten studies fulfilled the inclusion criteria and 2709 patients were evaluated. The overall analysis revealed a significant improvement in change of total UPDRS scores in 1 mg/day and 2 mg/day rasagiline groups compared to placebo. Significant improvement in Part I (Mentation) of UPDRS scores was observed in 1 mg/day, but not in 2 mg/day rasagiline treatment group. Part II (ADL) and Part III (Motor) subscales significantly improved with both doses of rasagiline. Both monotherapy and combination therapy significantly improved total UPDRS scores. Our results confirm the efficacy of rasagiline in PD. Further studies are required to establish the optimal dose of rasagiline, as well as to determine its effectiveness in different combination therapy protocols. KEY MESSAGES Rasagiline treatment was associated with significant improvement of UPDRS scores and the scores of the subscales. Both monotherapy and combination therapy significantly improved total UPDRS scores. Effect of rasagiline on total UPDRS scores was not dose-dependent.

Using research literature to develop a perceptual retraining treatment protocol.

PubMed

Neistadt, M E

1994-01-01

Treatment protocols derived from research literature can help therapists provide more rigorous treatment and more systematic assessment of client progress. This study applied research findings about the influence of task, subject, and feedback parameters on adult performance with block designs to an occupational therapy treatment protocol for parquetry block assembly--an activity occupational therapists use to remediate constructional deficits. Task parameter research suggests that parquetry tasks can be graded according to the features of the design cards, with cards having all block boundaries drawn in being easier than those with some block boundaries omitted. Subject parameter findings suggest that clients' lesions and initial constructional competence can influence their approaches to parquetry tasks. Feedback parameter research suggests that a combination of perceptual and planning cues is most effective for parquetry tasks. Methods to help clients transfer constructional skills from parquetry to functional tasks are also discussed.

Management of elderly patients with glioblastoma-multiforme-a systematic review.

PubMed

Almadani, Asmaa; Sanjay, Dixit; Chris, Rowland-Hill; Shailendra, Achawal; Chitoor, Rajaraman; Gerry, O'Reilly; Robin, Highley; Masood, Hussain; Louise, Baker; Lynne, Gill; Holly, Morris; Mohan, Hingorani

2018-03-09

The management of elderly patients with glioblastoma-multiforme (GBM) remains poorly defined with many experts in the past advocating best supportive care, in view of limited evidence on efficacy of more aggressive treatment protocols. There is randomised evidence (NORDIC and NA-O8 studies) to support the use of surgery followed by adjuvant monotherapy with either radiotherapy (RT) using hypofractionated regimes (e.g. 36 Gy in 6 fractions OR 40 Gy in 15 fractions) or chemotherapy with temozolomide (TMZ) in patients expressing methylation of promoter for O 6 -methylguanine-DNA methyltransferase enzyme. However, the role of combined-modality therapy involving the use of combined RT and TMZ protocols has remained controversial with data from the EORTC (European Organisation for Research and Treatment of Cancer)-NCIC (National Cancer Institute of Canada) studies indicating that patients more than 65 years of age may not benefit significantly from combining standard RT fractionation using 60 Gy in 30 fractions with concurrent and adjuvant TMZ. More recently, randomised data has emerged on combining hypofractionated RT with concurrent and adjuvant TMZ. We provide a comprehensive review of literature with the aim of defining an evidence-based algorithm for management of elderly glioblastoma-multiforme population.

Comparison of efficacy and tolerance between combination therapy and monotherapy as first-line chemotherapy in elderly patients with advanced gastric cancer: Study protocol for a randomized controlled trial.

PubMed

Lee, Keun-Wook; Zang, Dae Young; Ryu, Min-Hee; Kim, Ki Hyang; Kim, Mi-Jung; Han, Hye Sook; Koh, Sung Ae; Park, Jin Hyun; Kim, Jin Won; Nam, Byung-Ho; Choi, In Sil

2017-12-01

The combination of a fluoropyrimidine [5-fluorouracil (5-FU), capecitabine, or S-1] with a platinum analog (cisplatin or oxaliplatin) is the most widely accepted first-line chemotherapy regimen for metastatic or recurrent advanced gastric cancer (AGC), based on the results of clinical trials. However, there is little evidence to guide chemotherapy for elderly patients with AGC because of under-representation of this age group in clinical trials. Thus, the aim of this study is to determine the optimal chemotherapy regimen for elderly patients with AGC by comparing the efficacies and safeties of combination therapy versus monotherapy as first-line chemotherapy. This study is a randomized, controlled, multicenter, phase III trial. A total of 246 elderly patients (≥70 years old) with metastatic or recurrent AGC who have not received previous palliative chemotherapy will be randomly allocated to a combination therapy group or a monotherapy group. Patients randomized to the combination therapy group will receive fluoropyrimidine plus platinum combination chemotherapy (capecitabine/cisplatin, S-1/cisplatin, capecitabine/oxaliplatin, or 5-FU/oxaliplatin), and those randomized to the monotherapy group will receive fluoropyrimidine monotherapy (capecitabine, S-1, or 5-FU). The primary outcome is the overall survival of patients in each treatment group. The secondary outcomes include progression-free survival, response rate, quality of life, and safety. We are conducting this pragmatic trial to determine whether elderly patients with AGC will obtain the same benefit from chemotherapy as younger patients. We expect that this study will help guide decision-making for the optimal treatment of elderly patients with AGC.

Quality and Variability of Online Physical Therapy Protocols for Isolated Meniscal Repairs.

PubMed

Trofa, David P; Parisien, Robert L; Noticewala, Manish S; Noback, Peter C; Ahmad, Christopher S; Moutzouros, Vasilios; Makhni, Eric C

2018-05-31

The ideal meniscal repair postoperative rehabilitation protocol has yet to be determined. Further, patients are attempting to access health care content online at a precipitously increasing rate given the efficiency of modern search engines. The purpose of this investigation was to assess the quality and variability of meniscal repair rehabilitation protocols published online with the hypothesis that there would be a high degree of variability found across available protocols. To this end, Web-based meniscal repair physical therapy protocols from U.S. academic orthopaedic programs as well as the first 10 protocols identified by the Google search engine for the term "meniscal repair physical therapy protocol" were reviewed and assessed via a custom scoring rubric. Twenty protocols were identified from 155 U.S. academic orthopaedic programs for a total of 30 protocols. Twenty-six protocols (86.6%) recommended immediate postoperative bracing. Twelve (40.0%) protocols permitted immediate weight-bearing as tolerated (WBAT) postoperatively, while the remaining protocols permitted WBAT at an average of 4.0 (range, 1-7) weeks. There was considerable variation in range of motion (ROM) goals, with most protocols (73.3%) initiating immediate passive ROM to 90°. The types and timing of strength, proprioception, agility, and pivoting exercises advised were extremely diverse. Only five protocols (16.7%) employed functional testing as a marker for return to athletics. The results of this study indicate that only a minority of academic orthopaedic programs publish meniscal repair physical therapy protocols online and that within the most readily available online protocols there are significant disparities in regards to brace use, ROM, weight-bearing, and strengthening and proprioception exercises. These discrepancies reflect the fact that the best rehabilitation practices after a meniscal repair have yet to be elucidated. This represents a significant area for improved patient care through standardization. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Gene delivery strategies for the treatment of mucopolysaccharidoses.

PubMed

Baldo, Guilherme; Giugliani, Roberto; Matte, Ursula

2014-03-01

Mucopolysaccharidosis (MPS) disorders are genetic diseases caused by deficiencies in the lysosomal enzymes responsible for the degradation of glycosaminoglycans. Current treatments are not able to correct all disease symptoms and are not available for all MPS types, which makes gene therapy especially relevant. Multiple gene therapy approaches have been tested for different types of MPS, and our aim in this study is to critically analyze each of them. In this review, we have included the major studies that describe the use of adeno-associated retroviral and lentiviral vectors, as well as relevant non-viral approaches for MPS disorders. Some protocols such as the use of adeno-associated vectors and lentiviral vectors are approaching the clinic for these disorders and, along with combined approaches, seem to be the future of gene therapy for MPS.

Robotic upper limb rehabilitation after acute stroke by NeReBot: evaluation of treatment costs.

PubMed

Stefano, Masiero; Patrizia, Poli; Mario, Armani; Ferlini, Gregorio; Rizzello, Roberto; Rosati, Giulio

2014-01-01

Stroke is the first cause of disability. Several robotic devices have been developed for stroke rehabilitation. Robot therapy by NeReBot is demonstrated to be an effective tool for the treatment of poststroke paretic upper limbs, able to improve the activities of daily living of stroke survivors when used both as additional treatment and in partial substitution of conventional rehabilitation therapy in the acute and subacute phases poststroke. This study presents the evaluation of the costs related to delivering such therapy, in comparison with conventional rehabilitation treatment. By comparing several NeReBot treatment protocols, made of different combinations of robotic and nonrobotic exercises, we show that robotic technology can be a valuable and economically sustainable aid in the management of poststroke patient rehabilitation.

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

Pachauri, Vidhu; Saxena, Geetu; Mehta, Ashish

Lead, a ubiquitous and potent neurotoxicant causes oxidative stress which leads to numerous neurobehavioral and physiological alterations. The ability of lead to bind sulfhydryl groups or compete with calcium could be one of the reasons for its debilitating effects. In the present study, we addressed: i) if chelation therapy could circumvent the altered oxidative stress and prevent neuronal apoptosis in chronic lead-intoxicated rats, ii) whether chelation therapy could reverse biochemical and behavioral changes, and iii) if mono or combinational therapy with captopril (an antioxidant) and thiol chelating agents (DMSA/MiADMSA) is more effective than individual thiol chelator in lead-exposed rats. Resultsmore » indicated that lead caused a significant increase in reactive oxygen species, nitric oxide, and intracellular free calcium levels along with altered behavioral abnormalities in locomotor activity, exploratory behavior, learning, and memory that were supported by changes in neurotransmitter levels. A fall in membrane potential, release of cytochrome c, and DNA damage indicated mitochondrial-dependent apoptosis. Most of these alterations showed significant recovery following combined therapy with captopril with MiADMSA and to a smaller extend with captopril + DMSA over monotherapy with these chelators. It could be concluded from our present results that co-administration of a potent antioxidant (like captopril) might be a better treatment protocol than monotherapy to counter lead-induced oxidative stress. The major highlight of the work is an interesting experimental evidence of the efficacy of combinational therapy using an antioxidant with a thiol chelator in reversing neurological dystrophy caused due to chronic lead exposure in rats.« less

Nanotechnology applied to treatment of mucopolysaccharidoses.

PubMed

Schuh, Roselena S; Baldo, Guilherme; Teixeira, Helder F

2016-12-01

Mucopolysaccharidoses (MPS) are genetic disorders caused by the accumulation of glycosaminoglycans due to deficiencies in the lysosomal enzymes responsible for their catabolism. Current treatments are not fully effective and are not available for all MPS types. Accordingly, researchers have tested novel therapies for MPS, including nanotechnology-based enzyme delivery systems and gene therapy. In this review, we aim to analyze some of the approaches involving nanotechnology as alternative treatments for MPS. Areas covered: We analyze nanotechnology-based systems, focusing on the biomaterials, such as polymers and lipids, that comprise these nanostructures, and we have highlighted studies that describe their use as enzyme and gene delivery systems for the treatment of MPS diseases. Expert opinion: Some protocols, such as the use of polymer-based systems or nanostructured carriers associated with enzymes and nanotechnology-based carriers for gene therapy, along with combined approaches, seem to be the future of MPS therapy.

[Effects of functional electrical therapy on upper extremity functional motor recovery in patients after stroke--our experience and future directions].

PubMed

Plavsić, Aleksandra; Svirtlih, Laslo; Stefanović, Aleksandra; Jović, Stevan; Durović, Aleksandar; Popović, Mirjana

2011-01-01

New neurorehabilitation together with conventional techniques provide methods and technologies for maximizing what is preserved from the sensory motor system after cerebrovascular insult. The rehabilitation technique named functional electrical therapy was investigated in more than 60 patients in acute, subacute and chronic phase after cerebrovascular insult. The functional sensory information generated by functional electrical therapy was hypothesized to result in the intensive functional brain training of the activities performed. Functional electrical therapy is a combination of functional exercise and electrical therapy. The functional electrical therapy protocol comprises voluntary movement of the paretic arm in synchrony with the electrically assisted hand functions in order to perform typical daily activities. The daily treatment of 30 minutes lasts three weeks. The outcome measures include several tests for the evaluation of arm/hand functionality: upper extremity function test, drawing test, modified Aschworth scale, motor activity log and passive range of movement. Results from our several clinical studies showed that functional electrical therapy, if applied in acute and subacute stroke patients, leads to faster and greater improvement of functioning of the hemiplegic arm/hand compared to the control group. The outcomes were significantly superior at all times after the treatment for the higher functioning group. Additional well-planned clinical studies are needed to determine the adequate dose of treatment (timing, duration, intensity) with functional electrical therapy regarding the patient's status. A combination with other techniques should be further investigated.

Combination therapy with GLP-1 receptor agonists and basal insulin: a systematic review of the literature

PubMed Central

Balena, R; Hensley, I E; Miller, S; Barnett, A H

2013-01-01

Treatment algorithms for type 2 diabetes call for intensification of therapy over time as the disease progresses and glycaemic control worsens. If diet, exercise and oral antihyperglycaemic medications (OAMs) fail to maintain glycaemic control then basal insulin is added and ultimately prandial insulin may be required. However, such an intensification strategy carries risk of increased hypoglycaemia and weight gain, both of which are associated with worse long-term outcomes. An alternative strategy is to intensify therapy by the addition of a short-acting glucagon-like peptide-1 receptor agonist (GLP-1 RA) rather than prandial insulin. Short-acting GLP-1 RAs such as exenatide twice daily are particularly effective at reducing postprandial glucose while basal insulin has a greater effect on fasting glucose, providing a physiological rationale for this complementary approach. This review analyzes the latest randomized controlled clinical trials of insulin/GLP-1 RA combination therapy and examines results from ‘real-world’ use of the combinations as reported through observational and clinical practice studies. The most common finding across all types of studies was that combination therapy improved glycaemic control without weight gain or an increased risk of hypoglycaemia. Many studies reported weight loss and a reduction in insulin use when a GLP-1 RA was added to existing insulin therapy. Overall, the relative degree of benefit to glycaemic control and weight was influenced by the insulin titration employed in conjunction with the GLP-1 RA. The greatest glycaemic benefits were observed in studies with structured titration of insulin to glycaemic targets while the greatest weight benefits were observed in studies with a protocol-specified focus on insulin sparing. The adverse event profile of GLP-1 RAs in the reviewed trials was similar to that reported with GLP-1 RAs as monotherapy or in combination with OAMs with gastrointestinal events being the most commonly reported. PMID:23061470

Impact of retreatment with an artemisinin-based combination on malaria incidence and its potential selection of resistant strains: study protocol for a randomized controlled clinical trial

PubMed Central

2013-01-01

Background Artemisinin-based combination therapy is currently recommended by the World Health Organization as first-line treatment of uncomplicated malaria. Recommendations were adapted in 2010 regarding rescue treatment in case of treatment failure. Instead of quinine monotherapy, it should be combined with an antibiotic with antimalarial properties; alternatively, another artemisinin-based combination therapy may be used. However, for informing these policy changes, no clear evidence is yet available. The need to provide the policy makers with hard data on the appropriate rescue therapy is obvious. We hypothesize that the efficacy of the same artemisinin-based combination therapy used as rescue treatment is as efficacious as quinine + clindamycin or an alternative artemisinin-based combination therapy, without the risk of selecting drug resistant strains. Design We embed a randomized, open label, three-arm clinical trial in a longitudinal cohort design following up children with uncomplicated malaria until they are malaria parasite free for 4 weeks. The study is conducted in both the Democratic Republic of Congo and Uganda and performed in three steps. In the first step, the pre-randomized controlled trial (RCT) phase, children aged 12 to 59 months with uncomplicated malaria are treated with the recommended first-line drug and constitute a cohort that is passively followed up for 42 days. If the patients experience an uncomplicated malaria episode between days 14 and 42 of follow-up, they are randomized either to quinine + clindamycin, or an alternative artemisinin-based combination therapy, or the same first-line artemisinin-based combination therapy to be followed up for 28 additional days. If between days 14 and 28 the patients experience a recurrent parasitemia, they are retreated with the recommended first-line regimen and actively followed up for another 28 additional days (step three; post-RCT phase). The same methodology is followed for each subsequent failure. In any case, all patients without an infection at day 28 are classified as treatment successes and reach a study endpoint. The RCT phase allows the comparison of the safety and efficacy of three rescue treatments. The prolonged follow-up of all children until they are 28 days parasite-free allows us to assess epidemiological-, host- and parasite-related predictors for repeated malaria infection. Trial registration NCT01374581 and PACTR201203000351114 PMID:24059911

Continuous passive motion and physical therapy (CPM) versus physical therapy (PT) versus delayed physical therapy (DPT) after surgical release for elbow contractures; a study protocol for a prospective randomized controlled trial.

PubMed

Viveen, Jetske; Doornberg, Job N; Kodde, Izaak F; Goossens, Pjotr; Koenraadt, Koen L M; The, Bertram; Eygendaal, Denise

2017-11-22

The elbow is prone to stiffness after trauma. To regain functional elbow motion several conservative- and surgical treatment options are available. Conservative treatment includes physical therapy, intra-articular injections with corticosteroids and a static progressive or dynamic splinting program. If conservative treatment fails, an operative release of the posttraumatic stiff elbow is often performed. The best Evidence-Based rehabilitation protocol for patients after an operative release is unknown to date and differs per surgeon, hospital and country. Options include early- or delayed motion supervised by a physical therapist, immediate continuous passive motion (CPM), (night) splinting and a static progressive or dynamic splinting program. The SET-Study (Stiff Elbow Trial) is a single-centre, prospective, randomized controlled trial. The primary objective of this study is to compare the active Range of Motion (ROM) (flexion arc and rotational arc) twelve months after surgery between three groups. The first group will receive in-hospital CPM in combination with early motion Physical Therapy (PT) supervised by a physical therapist, the second group will receive only in-hospital early motion PT supervised by a physical therapist and the third group will receive outpatient supervised PT from postoperative day seven till ten. Secondary outcome measures will be Patient Reported Outcome Measures (PROMs) including the Mayo Elbow Performance Score (MEPS), the Oxford Elbow Score (OES), the quick Disabilities of Arm, Shoulder and Hand (qDASH) score, Visual Analogue pain Scale in rest and activity (VAS), Pain Catastrophizing Scale (PCS), the Short Form (SF)-36, the Centre for Epidemiological Studies Depression Scale Revised (CESD-R) and the Work Rehabilitation Questionnaire (WORQ) for the upper limb. A successful completion of this trial will provide evidence on the best rehabilitation protocol in order to (re)gain optimal motion after surgical release of the stiff elbow. The trial is registered at the Dutch Trial Register: NTR6067 , 31-8-2016.

A model for optimizing delivery of targeted radionuclide therapies into resection cavity margins for the treatment of primary brain cancers.

PubMed

Raghavan, Raghu; Howell, Roger W; Zalutsky, Michael R

2017-06-01

Radionuclides conjugated to molecules that bind specifically to cancer cells are of great interest as a means to increase the specificity of radiotherapy. Currently, the methods to disseminate these targeted radiotherapeutics have been either systemic delivery or by bolus injection into the tumor or tumor resection cavity. Herein we model a potentially more efficient method of delivery, namely pressure-driven fluid flow, called convection-enhanced delivery (CED), where a device infuses the molecules in solution (or suspension) directly into the tissue of interest. In particular, we focus on the setting of primary brain cancer after debulking surgery, where the tissue margins surrounding the surgical resection cavity are infiltrated with tumor cells and the most frequent sites of tumor recurrence. We develop the combination of fluid flow, chemical kinetics, and radiation dose models needed to examine such protocols. We focus on Auger electron-emitting radionuclides (e.g. 67 Ga, 77 Br, 111 In, 125 I, 123 I, 193m Pt, 195m Pt) whose short range makes them ideal for targeted therapy in this setting of small foci of tumor spread within normal tissue. By solving these model equations, we confirm that a CED protocol is promising in allowing sufficient absorbed dose to destroy cancer cells with minimal absorbed dose to normal cells at clinically feasible activity levels. We also show that Auger emitters are ideal for this purpose while the longer range alpha particle emitters fail to meet criteria for effective therapy (as neither would energetic beta particle emitters). The model is used with simplified assumptions on the geometry and homogeneity of brain tissue to allow semi-analytic solutions to be displayed, and with the purpose of a first examination of this new delivery protocol proposed for radionuclide therapy. However, we emphasize that it is immediately extensible to personalized therapy treatment planning as we have previously shown for conventional CED, at the price of requiring a fully numerical computerized approach.

Low-frequency rTMS with language therapy over a 3-month period for sensory-dominant aphasia: case series of two post-stroke Japanese patients.

PubMed

Kakuda, Wataru; Abo, Masahiro; Uruma, Go; Kaito, Nobuyoshi; Watanabe, Motoi

2010-01-01

To examine the safety and feasibility of therapeutic application of low-frequency repetitive transcranial magnetic stimulation (rTMS) combined with language therapy for post-stroke patients with sensory-dominant aphasia. Two post-stroke Japanese patients with sensory-dominant aphasia were studied. In both patients, 10 sessions of 20-minute low-frequency rTMS with 1 Hz to the Wernicke's area were provided throughout 6-day hospitalization, followed by weekly outpatient rTMS treatment for 3 months. The language therapy was also provided through the period of in- and out-patient treatment. Language function was evaluated using the Token test and the Standard Language Test of Aphasia (SLTA) at the start and end of the in-patient treatment and the end of the outpatient treatment. The therapeutic protocol was well tolerated throughout the in- and out-patient treatments, without any adverse effects. The scores of the Token test and certain sub-categories of SLTA increased in both patients after the in-patient rTMS treatment. Persistent improvement of the score was noted over the 3-month post-discharge period. The proposed protocol of long-term application of low-frequency rTMS to the Wernicke's area and language therapy is considered a safe and feasible therapeutic approach for post-stroke patients with sensory-dominant aphasia.

Triple antimicrobial therapy and acid suppression in dogs with chronic vomiting and gastric Helicobacter spp.

PubMed

Leib, Michael S; Duncan, Robert B; Ward, Daniel L

2007-01-01

Helicobacter pylori is a common cause of gastritis and peptic ulcers in humans. Many dogs, including those with gastritis and chronic vomiting, are infected with Helicobacter spp. Triple antimicrobial therapy will eradicate Helicobacter infection, improve gastritis, and reduce clinical signs. The addition of acid suppression medication will not improve results. Twenty-four pet dogs with chronic vomiting and gastric Helicobacter spp. Dogs were randomly assigned to triple antimicrobial therapy with or without famotidine. Gastroduodenoscopy was performed 4 weeks and 6 months after therapy. Helicobacter spp status was determined by histologic assessment of gastric mucosal biopsy specimens. Eradication rates for each treatment were not significantly different and combined were 75 and 42.9% at 4 weeks and 6 months, respectively. A greater improvement in gastritis scores occurred in dogs that became Helicobacter spp negative. Overall, the frequency of vomiting was reduced by 86.4%, but there were no differences between treatments. Eradication rates of Helicobacter spp with both treatments were not significantly different. Eradication rates at 6 months were modest, and more effective treatments should be developed. Acid suppression is not a necessary component of treatment protocols for dogs. Eradication of gastric Helicobacter spp was associated with improvement in gastritis scores. Dramatic reduction of the vomiting frequency occurred with both treatment protocols. Gastric Helicobacter spp may cause or contribute to chronic vomiting and gastritis in some dogs.

Survival times for canine intranasal sarcomas treated with radiation therapy: 86 cases (1996-2011).

PubMed

Sones, Evan; Smith, Annette; Schleis, Stephanie; Brawner, William; Almond, Gregory; Taylor, Kathryn; Haney, Siobhan; Wypij, Jackie; Keyerleber, Michele; Arthur, Jennifer; Hamilton, Terrance; Lawrence, Jessica; Gieger, Tracy; Sellon, Rance; Wright, Zack

2013-01-01

Sarcomas comprise approximately one-third of canine intranasal tumors, however few veterinary studies have described survival times of dogs with histologic subtypes of sarcomas separately from other intranasal tumors. One objective of this study was to describe median survival times for dogs treated with radiation therapy for intranasal sarcomas. A second objective was to compare survival times for dogs treated with three radiation therapy protocols: daily-fractionated radiation therapy; Monday, Wednesday, and Friday fractionated radiation therapy; and palliative radiation therapy. Medical records were retrospectively reviewed for dogs that had been treated with radiation therapy for confirmed intranasal sarcoma. A total of 86 dogs met inclusion criteria. Overall median survival time for included dogs was 444 days. Median survival time for dogs with chondrosarcoma (n = 42) was 463 days, fibrosarcoma (n = 12) 379 days, osteosarcoma (n = 6) 624 days, and undifferentiated sarcoma (n = 22) 344 days. Dogs treated with daily-fractionated radiation therapy protocols; Monday, Wednesday and Friday fractionated radiation therapy protocols; and palliative radiation therapy protocols had median survival times of 641, 347, and 305 days, respectively. A significant difference in survival time was found for dogs receiving curative intent radiation therapy vs. palliative radiation therapy (P = 0.032). A significant difference in survival time was also found for dogs receiving daily-fractionated radiation therapy vs. Monday, Wednesday and Friday fractionated radiation therapy (P = 0.0134). Findings from this study support the use of curative intent radiation therapy for dogs with intranasal sarcoma. Future prospective, randomized trials are needed for confirmation of treatment benefits. © 2012 Veterinary Radiology & Ultrasound.

Renal Capsule Xenografting and Subcutaneous Pellet Implantation for the Evaluation of Prostate Carcinogenesis and Benign Prostatic Hyperplasia

PubMed Central

Nicholson, Tristan M.; Uchtmann, Kristen S.; Valdez, Conrad D.; Theberge, Ashleigh B.; Miralem, Tihomir; Ricke, William A.

2013-01-01

New therapies for two common prostate diseases, prostate cancer (PrCa) and benign prostatic hyperplasia (BPH), depend critically on experiments evaluating their hormonal regulation. Sex steroid hormones (notably androgens and estrogens) are important in PrCa and BPH; we probe their respective roles in inducing prostate growth and carcinogenesis in mice with experiments using compressed hormone pellets. Hormone and/or drug pellets are easily manufactured with a pellet press, and surgically implanted into the subcutaneous tissue of the male mouse host. We also describe a protocol for the evaluation of hormonal carcinogenesis by combining subcutaneous hormone pellet implantation with xenografting of prostate cell recombinants under the renal capsule of immunocompromised mice. Moreover, subcutaneous hormone pellet implantation, in combination with renal capsule xenografting of BPH tissue, is useful to better understand hormonal regulation of benign prostate growth, and to test new therapies targeting sex steroid hormone pathways. PMID:24022657

[Prognosis improvements in children with acute myelocytic leucemia after more intensive induction therapy (author's transl)].

PubMed

Scheer, U; Schellong, G; Riehm, H

1979-03-01

Between October 1974 and October 1978 23 children with acute myelocytic leucemia (AML) received intensive therapy in the Univ.-Kinderklinik Münster: 4 children were treated according to the ALGB-protocol consisting of 5-7 day courses of ARA-C-infusion and 3 DNR-injections. 19 patients received the West-Berlin-protocol: The first 7 the original ALL protocol, 11 the modified form of AML, which will be presented here as AML-therapy-study BFM 78. 4 of the 23 patients died with early acute cerebral bleeding. 2 patients were nonresponders. 17 children went into remission. One girl died in remission of septicemic aspergillosis. 4 children had a relapse. In November 1978 there were still 12 patients in continuous complete remission, 3 of them already without therapy. 13 of the 19 patients, who were treated with the West-Berlin-protocol went into remission. 1 had a relapse. At present there are 11 patients in continuous complete remission. The above results and those found in the literature could signify that the long term prognosis of children with AML will be improved. To coordinate efforts toward this goal a cooperative AML-therapy-study in the "Deutsche Arbeitsgemeinschaft für Leukämieforschung" (BFM-group) using the here presented therapy protocol was formed in November 1978.

Radiogenetic therapy: strategies to overcome tumor resistance.

PubMed

Marples, B; Greco, O; Joiner, M C; Scott, S D

2003-01-01

The aim of cancer gene therapy is to selectively kill malignant cells at the tumor site, by exploiting traits specific to cancer cells and/or solid tumors. Strategies that take advantage of biological features common to different tumor types are particularly promising, since they have wide clinical applicability. Much attention has focused on genetic methods that complement radiotherapy, the principal treatment modality, or that exploit hypoxia, the most ubiquitous characteristic of most solid cancers. The goal of this review is to highlight two promising gene therapy methods developed specifically to target the tumor volume that can be readily used in combination with radiotherapy. The first approach uses radiation-responsive gene promoters to control the selective expression of a suicide gene (e.g., herpes simplex virus thymidine kinase) to irradiated tissue only, leading to targeted cell killing in the presence of a prodrug (e.g., ganciclovir). The second method utilizes oxygen-dependent promoters to produce selective therapeutic gene expression and prodrug activation in hypoxic cells, which are refractive to conventional radiotherapy. Further refining of tumor targeting can be achieved by combining radiation and hypoxia responsive elements in chimeric promoters activated by either and dual stimuli. The in vitro and in vivo studies described in this review suggest that the combination of gene therapy and radiotherapy protocols has potential for use in cancer care, particularly in cases currently refractory to treatment as a result of inherent or hypoxia-mediated radioresistance.

Economical impact associated with a biological therapy prioritization protocol in patients with rheumatoid arthritis in the Hospital of Sagunto.

PubMed

Borrás-Blasco, Joaquín; Casterá, M Dolores-Elvira; Cortes, Xavier; Rosique-Robles, J Dolores; Abad, F Javier

2014-11-01

Until 2010 the cost of biological treatments in Rheumatoid Arthritis (RA) was increasing annually by 15% in our hospital. In 1st January 2011, a Hospital Commission of Biological Therapies involving rheumatology and pharmacy services was created to improve the management of biological drugs and a biological therapy prioritization protocol in RA patients was also established to improve the efficient usage of biological drugs in RA. To evaluate the economic impact associated with a biological therapy prioritization protocol for RA patients in the Hospital of Sagunto. Observational, ambispective study comparing the associated cost of RA patients treated with biological drugs in the pre-protocol (2009 - 2010) versus post-protocol periods (2011 - 2012). RA patients treated with Abatacept (ABA), Adalimumab (ADA), Etanercept (ETN) or Infliximab (IFX) for at least 6 months during the study period (2009 - 2012) were included. In 2012, Tocilizumab (TCZ) was also included in the prioritization protocol. Prioritization protocol was established based on both clinical and economical aspects and supervised case by case by our Commission. Cost savings and economic impact were calculated using Spanish official prices. In the pre-protocol period (2009 - 2010), total expenses were increasing by €110,000, up to €1,761,000 in 2010 (€11,362 pat/year). After protocol implementation, total expenses decreased by 53,676€ on the 2010 - 2011 period, and 149,200€ on the 2011 - 2012 period. On the 2010 - 2011 period the cost of biological therapy per patient-year decreased 355€ (11,007€ pat/year) and additional 653€ (up to 10,354€ pat/year) by 2012, with a cumulative effect of the protocol implementation of 1,008€ per patient-year. In the pre-protocol period (2009), the annual cost/patient was 10.812€ with ETN, 10.942€ with IFX, 12.961€ with ADA and 12.739€ with ABA. By 1st January 2013, the annual cost per patient was 9,469€ with ETN, 10,579€ with IFX, 11,117€ with ADA, 13,540€ with ABA and 14,932€ with TCZ. The creation of our Commission of Biological Therapies is key to rational management of RA patients and optimization of resources, allowing us to save 200,000€ after 2-year efficiency protocol implementation.

Options for investigative postsurgical therapy for gastric cancer, and case report of using the option for combined immunotherapy and chemotherapy.

PubMed

Gerhardt, P

2001-02-01

The investigative therapy for a senior patient after radical subtotal gastroesophagectomy for regional lymph node and proximal esophagus metastasized adenocarcinoma (stage IIIA, T3, N 1 M0) of the cardioesophageal junction is reported. The case has several unusual features: (1) the patient is the author and is not a physician; (2) in the absence of codified postsurgical treatment, he used his academic biomedical background, commercial associations, and international contacts to find and prioritize six clinically tested options for investigative postsurgical therapy; (3) after unsuccessful efforts to append ongoing clinical trials of new immunotherapies for breast adenocarcinoma (the first two therapy options), an innovative protocol was designed and gained allowance by the U.S. Food and Drug Administration for his use of combined nonspecific immunotherapy and chemotherapy based on extensive trials in South Korea that showed the synergistic effect of the two postsurgical therapies used together. A potent, new, nonspecific immunostimulant (DetoxPC) was injected subcutaneously in 10 diminishing doses during 105 weeks. Two standard chemotherapeutic drugs (5-fluorouracil and mitomycin-C) were injected intravenously in six equal doses during three weeks. Five years after the surgery, the patient enjoys good health without signs or symptoms of recurrence or metastasis. He discusses his perspectives on future clinical trials and on a patient actively pursuing investigative postsurgical therapy for a malignancy when otherwise poor survival is indicated.

A multidisciplinary TBI inpatient rehabilitation programme for active duty service members as part of a randomized clinical trial.

PubMed

Braverman, S E; Spector, J; Warden, D L; Wilson, B C; Ellis, T E; Bamdad, M J; Salazar, A M

1999-06-01

To design and describe an effective rehabilitation programme for use in an ongoing trial on the efficacy of multidisciplinary brain injury rehabilitation for moderately head injury military service members. Treatment arm of a randomized control trial. US military tertiary care hospital inpatient rehabilitation programme. Sixty seven active duty military with moderate to severe TBI who were randomized to the treatment arm of the protocol. Eight week rehabilitation programme combining group and individual therapies with an inpatient milieu-oriented neuropsychological focus. Group therapies included fitness, planning and organization, cognitive skills, work skills, medication, and milieu groups, and community re-entry outings. Individual therapy included neuropsychology, work therapy, occupational therapy, and speech and language pathology. Successful return to work and return to duty. At 1 year follow-up, 64 patients returned to work (96%) and 66% (44/67) returned to duty. The described rehabilitation programme demonstrates one successful effort to rehabilitate active duty military service members with TBI who have the potential to return to duty.

Current management of hepatocellular carcinoma: An Eastern perspective

PubMed Central

Yim, Hyung Joon; Suh, Sang Jun; Um, Soon Ho

2015-01-01

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer death, especially in Eastern areas. With advancements in diagnosis and treatment modalities for HCC, the survival and prognosis of HCC patients are improving. However, treatment patterns are not uniform between areas despite efforts to promote a common protocol. Although many hepatologists in Asian countries may adopt the principles of the Barcelona Clinic Liver Cancer staging system, they are also independently making an effort to expand the indications of each treatment and to combine therapies for better outcomes. Several expanded criteria for liver transplantation in HCC have been developed in Asian countries. Living donor liver transplantation is much more commonly performed in these countries than deceased donor liver transplantation, and it may be preceded by other treatments such as the down-staging of tumors. Local ablation therapies are often combined with transarterial chemoembolization (TACE) and the outcome is comparable to that of surgical resection. The indications of TACE are expanding, and there are new types of transarterial therapies. Although data on drug-eluting beads, TACE, and radioembolization in Asian countries are still relatively sparse compared with Western countries, these methods are gradually gaining popularity because of better tolerability and the possibility of improved response rates. Hepatic arterial infusion chemotherapy and radiotherapy are not included in Western guidelines, but are currently being used actively in several Asian countries. For more advanced HCCs, appropriate combinations of TACE, radiotherapy, and sorafenib can be considered, and emerging data indicate improved outcomes of combination therapies compared with single therapies. To include these paradigm shifts into newer treatment guidelines, more studies may be needed, but they are certainly in progress. PMID:25852267

Recommendations for In Vitro and In Vivo Testing of Magnetic Nanoparticle Hyperthermia Combined with Radiation Therapy †

PubMed Central

Costa Lima, Sofia A.; Bouziotis, Penelope; Vranješ-Djurić, Sanja; Efthimiadou, Eleni Κ.; Laurenzana, Anna; Barbosa, Ana Isabel; Jones, Carlton; Jankovic, Drina; Gobbo, Oliviero L.

2018-01-01

Magnetic nanoparticle (MNP)-mediated hyperthermia (MH) coupled with radiation therapy (RT) is a novel approach that has the potential to overcome various practical difficulties encountered in cancer treatment. In this work, we present recommendations for the in vitro and in vivo testing and application of the two treatment techniques. These recommendations were developed by the members of Working Group 3 of COST Action TD 1402: Multifunctional Nanoparticles for Magnetic Hyperthermia and Indirect Radiation Therapy (“Radiomag”). The purpose of the recommendations is not to provide definitive answers and directions but, rather, to outline those tests and considerations that a researcher must address in order to perform in vitro and in vivo studies. The recommendations are divided into 5 parts: (a) in vitro evaluation of MNPs; (b) in vitro evaluation of MNP-cell interactions; (c) in vivo evaluation of the MNPs; (d) MH combined with RT; and (e) pharmacokinetic studies of MNPs. Synthesis and characterization of the MNPs, as well as RT protocols, are beyond the scope of this work. PMID:29734795

Recommendations for In Vitro and In Vivo Testing of Magnetic Nanoparticle Hyperthermia Combined with Radiation Therapy.

PubMed

Spirou, Spiridon V; Costa Lima, Sofia A; Bouziotis, Penelope; Vranješ-Djurić, Sanja; Efthimiadou, Eleni Κ; Laurenzana, Anna; Barbosa, Ana Isabel; Garcia-Alonso, Ignacio; Jones, Carlton; Jankovic, Drina; Gobbo, Oliviero L

2018-05-06

Magnetic nanoparticle (MNP)-mediated hyperthermia (MH) coupled with radiation therapy (RT) is a novel approach that has the potential to overcome various practical difficulties encountered in cancer treatment. In this work, we present recommendations for the in vitro and in vivo testing and application of the two treatment techniques. These recommendations were developed by the members of Working Group 3 of COST Action TD 1402: Multifunctional Nanoparticles for Magnetic Hyperthermia and Indirect Radiation Therapy ("Radiomag"). The purpose of the recommendations is not to provide definitive answers and directions but, rather, to outline those tests and considerations that a researcher must address in order to perform in vitro and in vivo studies. The recommendations are divided into 5 parts: (a) in vitro evaluation of MNPs; (b) in vitro evaluation of MNP-cell interactions; (c) in vivo evaluation of the MNPs; (d) MH combined with RT; and (e) pharmacokinetic studies of MNPs. Synthesis and characterization of the MNPs, as well as RT protocols, are beyond the scope of this work.

Effects of botulinum toxin A therapy and multidisciplinary rehabilitation on upper and lower limb spasticity in post-stroke patients.

PubMed

Hara, Takatoshi; Abo, Masahiro; Hara, Hiroyoshi; Kobayashi, Kazushige; Shimamoto, Yusuke; Samizo, Yuta; Sasaki, Nobuyuki; Yamada, Naoki; Niimi, Masachika

2017-06-01

The purpose of this study was to examine the effects of combined botulinum toxin type A (BoNT-A) and inpatient multidisciplinary (MD) rehabilitation therapy on the improvement of upper and lower limb function in post-stroke patients. In this retrospective study, a 12-day inpatient treatment protocol was implemented on 51 post-stroke patients with spasticity. Assessments were performed on the day of admission, at discharge, and at 3 months following discharge. At the time of discharge, all of the evaluated items showed a statistically significant improvement. Only the Functional Reach Test (FRT) showed a statistically significant improvement at 3 months. In subgroup analyses, the slowest walking speed group showed a significantly greater change ratio of the 10 Meter Walk Test relative to the other groups, from the time of admission to discharge. This group showed a greater FRT change ratio than the other groups from the time of admission to the 3-month follow-up. Inpatient combined therapy of simultaneous injections of BoNT-A to the upper and lower limbs and MD may improve motor function.

Ultrasonography-driven combination antibiotic therapy with tigecycline significantly increases survival among patients with neutropenic enterocolitis following cytarabine-containing chemotherapy for the remission induction of acute myeloid leukemia.

PubMed

Pugliese, Novella; Salvatore, Paola; Iula, Dora Vita; Catania, Maria Rosaria; Chiurazzi, Federico; Della Pepa, Roberta; Cerchione, Claudio; Raimondo, Marta; Giordano, Claudia; Simeone, Luigia; Caruso, Simona; Pane, Fabrizio; Picardi, Marco

2017-07-01

Neutropenic enterocolitis (NEC) is an abdominal infection reported primarily in patients with acute myeloid leukemia (AML) following chemotherapy, especially cytarabine, a notable efficacious cytotoxic agent for AML remission. Specific data regarding the impact of different cytarabine schedules and/or antibacterial regimens for NEC are sparse. The aim of the study was to identify the predictors of outcome within 30 days of NEC onset. NEC episodes were retrospectively pinpointed among 440 patients with newly diagnosed AML hospitalized in our Institution, over a 10-year period, for receiving chemotherapy protocols with 100-6000 mg/m 2 daily of cytarabine. Two subgroups, survivors versus nonsurvivors, were compared by using logistic regression analysis. NEC was documented in 100 of 420 (23.8%) analyzed patients: 42.5% had received high-dose cytarabine, whereas 19% and 15% intermediate-dose and standard-dose cytarabine, respectively (P < 0.001). The 30-day NEC attributable mortality rate was 23%. In univariate analysis, antileukemic protocols containing robust dosages of cytarabine were significantly associated with high mortality (P < 0.001); whereas, standard-dose cytarabine and prompt initiation (at the ultrasonographic appearance of intestinal mural thickening) of NEC therapy with antibiotic combinations including tigecycline were significantly associated with low mortality. In multivariate analysis, high-dose cytarabine-containing chemotherapy was the independent predictor of poor outcome (odds ratio [OR]: 0.109; 95% confidence interval [CI]: 0.032-0.364; P < 0.001), whereas ultrasonography-driven NEC therapy with antibiotic regimens including tigecycline was associated with a favorable outcome (OR: 13.161; 95% CI: 1.587-109.17; P = 0.017). Chemotherapy schedules with robust dosages of cytarabine for AML remission are associated with a high rate of NEC incidence and attributable. Vigorous antibacterial therapy, triggered off pathologic ultrasonographic findings, with drug combinations which have broad antimicrobial coverage and good gut penetration, specifically those also including tigecycline, may be effective in improving 30-day survival rate after NEC onset. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Cognitive behavior therapy may sustain antidepressant effects of intravenous ketamine in treatment-resistant depression

PubMed Central

Wilkinson, Samuel T.; Wright, DaShaun; Fasula, Madonna K.; Fenton, Lisa; Griepp, Matthew; Ostroff, Robert B.; Sanacora, Gerard

2017-01-01

Introduction Ketamine has shown rapid though short-lived antidepressant effects. The possibility of concerning neurobiological changes following repeated exposure to the drug motivate the development of strategies that obviate or minimize the need for longer-term treatment with ketamine. In this open-label trial, we investigated whether cognitive behavioral therapy (CBT) can sustain or extend ketamine's antidepressant effects. Methods Patients who were pursuing ketamine infusion therapy for treatment-resistant depression (TRD) were invited to participate in the study. If enrolled, the subjects initiated a 12-session, 10-week course of CBT concurrently with a short 4-treatment, 2-week course of intravenous ketamine (0.5mg/kg infused over 40 mins) provided under a standardized clinical protocol. Results Sixteen participants initiated the protocol, with 8 (50%) attaining a response to the ketamine and 7 (43.8%) achieving remission during the first two weeks of protocol. Among ketamine responders, the relapse rate at the end of the CBT course (8 weeks following the last ketamine exposure) was 25% (2/8). On longer-term follow up, 5 of 8 subjects eventually relapsed, the median time-to-relapse being 12 weeks following ketamine exposure. Among ketamine remitters, 3 of 7 retained remission until at least 4 weeks following the last ketamine exposure, with 2 retaining remission through 8 weeks following ketamine exposure. Ketamine non-responders did not appear to benefit from CBT. Conclusions CBT may sustain the antidepressant effects of ketamine in TRD. Well-powered randomized controlled trials are warranted to further investigate this treatment combination as a way to sustain ketamine's antidepressant effects. PMID:28490030

Combined MI + CBT for Depressive Symptoms and Binge Drinking Among Young Adults: Two Case Studies

PubMed Central

Pedrelli, Paola; Borsari, Brian; Palm, Kathleen M.; Dalton, Elizabeth; Fava, Maurizio

2014-01-01

There are high rates of comorbidity between heavy drinking and depressive symptoms among college students, often resulting in severe alcohol-related consequences. No empirically supported treatment exists that concurrently addresses both of these problems in this population. Research with college students has demonstrated that brief motivational interventions (BMIs) reduce heavy drinking and alcohol-related consequences, and that cognitive behavioral therapy for depression (CBT-D) is effective in reducing depressive symptoms. Thus, a program combining BMI and CBT-D appears ideal for college students with co-occurring binge drinking and depressive symptoms. This manuscript presents the rationale and format of a BMI + CBT-D treatment protocol for this population, and provides a case example of a female college student who received the protocol and experienced improvement in depressive symptoms, a reduction in alcohol use and alcohol-related negative consequences, and an increase in readiness to change alcohol consumption. We discuss theoretical and clinical implications of these findings, and suggest directions for future research. PMID:25170188

Accelerating Pediatric Cancer Drug Development: Challenges and Opportunities for Pediatric Master Protocols.

PubMed

Khan, Tahira; Stewart, Mark; Blackman, Samuel; Rousseau, Raphaël; Donoghue, Martha; Cohen, Kenneth; Seibel, Nita; Fleury, Mark; Benettaib, Bouchra; Malik, Raleigh; Vassal, Gilles; Reaman, Gregory

2018-01-01

Although outcomes for children with cancer have significantly improved over the past 40 years, there has been little progress in the treatment of some pediatric cancers, particularly when advanced. Additionally, clinical trial options and availability are often insufficient. Improved genomic and immunologic understanding of pediatric cancers, combined with innovative clinical trial designs, may provide an enhanced opportunity to study childhood cancers. Master protocols, which incorporate the use of precision medicine approaches, coupled with the ability to quickly assess the safety and effectiveness of new therapies, have the potential to accelerate early-phase clinical testing of novel therapeutics and which may result in more rapid approval of new drugs for children with cancer. Designing and conducting master protocols for children requires addressing similar principles and requirements as traditional adult oncology trials, but there are also unique considerations for master protocols conducted in children with cancer. The purpose of this paper is to define the key challenges and opportunities associated with this approach in order to ensure that master protocols can be adapted to benefit children and adolescents and ensure that adequate data are captured to advance, in parallel, the clinical development of investigational agents for children with cancer.

Blending online therapy into regular face-to-face therapy for depression: content, ratio and preconditions according to patients and therapists using a Delphi study.

PubMed

van der Vaart, Rosalie; Witting, Marjon; Riper, Heleen; Kooistra, Lisa; Bohlmeijer, Ernst T; van Gemert-Pijnen, Lisette J E W C

2014-12-14

Blending online modules into face-to-face therapy offers perspectives to enhance patient self-management and to increase the (cost-)effectiveness of therapy, while still providing the support patients need. The aim of this study was to outline optimal usage of blended care for depression, according to patients and therapists. A Delphi method was used to find consensus on suitable blended protocols (content, sequence and ratio). Phase 1 was an explorative phase, conducted in two rounds of online questionnaires, in which patients' and therapists' preferences and opinions about online psychotherapy were surveyed. In phase 2, data from phase 1 was used in face-to-face interviews with therapists to investigate how blended therapy protocols could be set up and what essential preconditions would be. Twelve therapists and nine patients completed the surveys. Blended therapy was positively perceived among all respondents, especially to enhance the self-management of patients. According to most respondents, practical therapy components (assignments, diaries and psycho-education) may be provided via online modules, while process-related components (introduction, evaluation and discussing thoughts and feelings), should be supported face-to-face. The preferred blend of online and face-to-face sessions differs between therapists and patients; most therapists prefer 75% face-to-face sessions, most patients 50 to 60%. The interviews showed that tailoring treatment to individual patients is essential in secondary mental health care, due to the complexity of their problems. The amount and ratio of online modules needs to be adjusted according to the patient's problems, skills and characteristics. Therapists themselves should also develop skills to integrate online and face-to-face sessions. Blending online and face-to-face sessions in an integrated depression therapy is viewed as a positive innovation by patients and therapists. Following a standard blended protocol, however, would be difficult in secondary mental health care. A database of online modules could provide flexibility to tailor treatment to individual patients, which asks motivation and skills of both patients and therapists. Further research is necessary to determine the (cost-)effectiveness of blended care, but this study provides starting points and preconditions to blend online and face-to-face sessions and create a treatment combining the best of both worlds.

Attempted photodynamic therapy against patagial squamous cell carcinoma in an African rose-ringed parakeet (Psittacula krameri).

PubMed

Suedmeyer, Wm Kirk; Henry, Carolyn; McCaw, Dudley; Boucher, Magalie

2007-12-01

A 5-yr-old female African rose-ringed parakeet (Psittacula krameri) presented with an ulcerated mass in the medial postpatagial area of the right wing. Biopsy specimens of the mass demonstrated a well-differentiated squamous cell carcinoma. Photodynamic therapy resulted in tumor cell necrosis and initial reduction in tumor burden, but complete remission was not achieved. Based on this and other avian cases, it appears that photodynamic therapy designed to eradicate squamous cell carcinoma in avian species using protocols modeled after canine, feline, and human photodynamic therapy protocols may not be useful. It is hypothesized that differences in light penetration, photosensitizing agent pharmacokinetics, and wound healing properties in avian species necessitate alteration of photodynamic therapy protocols if this treatment modality is to be effective in avian oncology.

Trial Protocol: Cognitive functional therapy compared with combined manual therapy and motor control exercise for people with non-specific chronic low back pain: protocol for a randomised, controlled trial.

PubMed

Belache, Fabiana Terra Cunha; Souza, Cíntia Pereira de; Fernandez, Jessica; Castro, Julia; Ferreira, Paula Dos Santos; Rosa, Elizana Rodrigues de Sousa; Araújo, Nathalia Cristina Gimenez de; Reis, Felipe José Jandre; Almeida, Renato Santos de; Nogueira, Leandro Alberto Calazans; Correia, Luís Cláudio Lemos; Meziat-Filho, Ney

2018-06-11

Chronic low back pain is a public health problem, and there is strong evidence that it is associated with a complex interaction of biopsychosocial factors. Cognitive functional therapy is an intervention that deals with potentially modifiable multidimensional aspects of pain (eg, provocative cognitive, movement and lifestyle behaviours). There is evidence (from a single randomised, controlled trial) that cognitive functional therapy is better than combined manual therapy and motor control exercise. However, this study had significant methodological shortcomings including the failure to carry out an intention-to-treat analysis and a considerable loss of follow-up of participants. It is important to replicate this study in another domain through a randomised clinical trial with similar objectives but correcting these methodological shortcomings. To investigate the efficacy of cognitive functional therapy compared to combined manual therapy and exercise on pain and disability at 3 months in patients with chronic non-specific low back pain. Two-group, randomised, multicentre controlled trial with blinded assessors. One hundred and forty-eight participants with chronic low back pain that has persisted for >3months and no specific spinal pathology will be recruited from the school clinic of the Centro Universitário Augusto Motta and a private clinic in the city of Rio de Janeiro, Brazil. Four to 10 sessions of cognitive functional therapy. The physiotherapists who will treat the participants in the cognitive functional therapy group have previously attended 2 workshops with two different tutors of the method. Such physiotherapists have completed 106 hours of training, including workshops and patient examinations, as well as conducting a pilot study under the supervision of another physiotherapist with>3 years of clinical experience in cognitive functional therapy. Four to 10 sessions of combined manual therapy and motor control exercises. Participants in the combined manual therapy and exercise group will be treated by two physiotherapists with an average of >10years of clinical experience in manual therapy and motor control exercises, including isolated contractions of the deep abdominal muscles. The primary outcome measures will be pain intensity and disability 3 months after randomisation. Secondary outcomes will be pain and disability assessed 6 and 12 months after randomisation, and both global perceived effect and patient satisfaction at 3, 6 and 12 months after randomisation. The potential outcome mediators will be assessed at 3 and 6 months after randomisation, with brief screening questions for anxiety, social isolation, catastrophisation, depression, fear of movement, stress and sleep. Non-specific predictors and moderators will include age, gender, duration of chronic low back pain, chronicity risk (Örebro and Start Back score), number of pain areas, stressful life event, MRI scan imaging, and family history. Intention-to-treat analysis will be performed. Linear mixed models will be used to compare the mean differences in pain intensity, disability and global perceived effect between the intervention arms. The analysis of the effect of potential mediators of the treatment will be performed using the causal mediation methods described by Imai and colleagues. The baseline variables will be evaluated as predictors and moderators of treatment, including terms and interaction models. A level of statistical significance of 5% will be used in the analysis. All the analyses will be performed using RStudio. This study will investigate whether the results of the first cognitive functional therapy randomised clinical trial are reproducible. The present study will have a sample size capable of detecting clinically relevant effects of the treatment with a low risk of bias. In pragmatic terms, this clinical trial is designed to reproduce the intervention as it would be performed in clinical practice by a trained physiotherapist who works with cognitive functional therapy, which increases the relevance of this study. The combined manual therapy and exercise group comprises an intervention strategy widely used by physiotherapists to treat low back pain. As evidence of efficacy is still limited, the results of a randomised, controlled clinical trial of high methodological quality will help physiotherapists in clinical decision-making. Copyright © 2018 Australian Physiotherapy Association. Published by Elsevier B.V. All rights reserved.

Lentiviral-mediated genetic correction of hematopoietic and mesenchymal progenitor cells from Fanconi anemia patients.

PubMed

Jacome, Ariana; Navarro, Susana; Río, Paula; Yañez, Rosa M; González-Murillo, Africa; Lozano, M Luz; Lamana, Maria Luisa; Sevilla, Julian; Olive, Teresa; Diaz-Heredia, Cristina; Badell, Isabel; Estella, Jesus; Madero, Luis; Guenechea, Guillermo; Casado, José; Segovia, Jose C; Bueren, Juan A

2009-06-01

Previous clinical trials based on the genetic correction of purified CD34(+) cells with gamma-retroviral vectors have demonstrated clinical efficacy in different monogenic diseases, including X-linked severe combined immunodeficiency, adenosine deaminase deficient severe combined immunodeficiency and chronic granulomatous disease. Similar protocols, however, failed to engraft Fanconi anemia (FA) patients with genetically corrected cells. In this study, we first aimed to correlate the hematological status of 27 FA patients with CD34(+) cell values determined in their bone marrow (BM). Strikingly, no correlation between these parameters was observed, although good correlations were obtained when numbers of colony-forming cells (CFCs) were considered. Based on these results, and because purified FA CD34(+) cells might have suboptimal repopulating properties, we investigated the possibility of genetically correcting unselected BM samples from FA patients. Our data show that the lentiviral transduction of unselected FA BM cells mediates an efficient phenotypic correction of hematopoietic progenitor cells and also of CD34(-) mesenchymal stromal cells (MSCs), with a reported role in hematopoietic engraftment. Our results suggest that gene therapy protocols appropriate for the treatment of different monogenic diseases may not be adequate for stem cell diseases like FA. We propose a new approach for the gene therapy of FA based on the rapid transduction of unselected hematopoietic grafts with lentiviral vectors (LVs).

Lentiviral-mediated Genetic Correction of Hematopoietic and Mesenchymal Progenitor Cells From Fanconi Anemia Patients

PubMed Central

Jacome, Ariana; Navarro, Susana; Río, Paula; Yañez, Rosa M; González-Murillo, Africa; Luz Lozano, M; Lamana, Maria Luisa; Sevilla, Julian; Olive, Teresa; Diaz-Heredia, Cristina; Badell, Isabel; Estella, Jesus; Madero, Luis; Guenechea, Guillermo; Casado, José; Segovia, Jose C; Bueren, Juan A

2009-01-01

Previous clinical trials based on the genetic correction of purified CD34+ cells with γ-retroviral vectors have demonstrated clinical efficacy in different monogenic diseases, including X-linked severe combined immunodeficiency, adenosine deaminase deficient severe combined immunodeficiency and chronic granulomatous disease. Similar protocols, however, failed to engraft Fanconi anemia (FA) patients with genetically corrected cells. In this study, we first aimed to correlate the hematological status of 27 FA patients with CD34+ cell values determined in their bone marrow (BM). Strikingly, no correlation between these parameters was observed, although good correlations were obtained when numbers of colony-forming cells (CFCs) were considered. Based on these results, and because purified FA CD34+ cells might have suboptimal repopulating properties, we investigated the possibility of genetically correcting unselected BM samples from FA patients. Our data show that the lentiviral transduction of unselected FA BM cells mediates an efficient phenotypic correction of hematopoietic progenitor cells and also of CD34− mesenchymal stromal cells (MSCs), with a reported role in hematopoietic engraftment. Our results suggest that gene therapy protocols appropriate for the treatment of different monogenic diseases may not be adequate for stem cell diseases like FA. We propose a new approach for the gene therapy of FA based on the rapid transduction of unselected hematopoietic grafts with lentiviral vectors (LVs). PMID:19277017

Impact of the introduction of a standardised ICD programming protocol: real-world data from a single centre.

PubMed

Sunderland, Nicholas; Kaura, Amit; Li, Anthony; Kamdar, Ravi; Petzer, Ed; Dhillon, Para; Murgatroyd, Francis; Scott, Paul A

2016-09-01

Randomised trials have shown that empiric ICD programming, using long detection times and high detection zones, reduces device therapy in ICD recipients. However, there is less data on its effectiveness in a "real-world" setting, especially secondary prevention patients. Our aim was to evaluate the introduction of a standardised programming protocol in a real-world setting of unselected ICD recipients. We analysed 270 consecutive ICD recipients implanted in a single centre-135 implanted prior to protocol implementation (physician-led group) and 135 after (standardised group). The protocol included long arrhythmia detection times (30/40 or equivalent) and high rate detection zones (primary prevention lower treatment zone 200 bpm). Programming in the physician-led group was at the discretion of the implanter. The primary endpoint was time-to-any therapy (ATP or shocks). Secondary endpoints were time-to-inappropriate therapy and time-to-appropriate therapy. The safety endpoints were syncopal episodes, hospital admissions and death. At 12 months follow-up, 47 patients had received any ICD therapy (physician-led group, n = 31 vs. standardised group, n = 16). There was a 47 % risk reduction in any device therapy (p = 0.04) and an 86 % risk reduction in inappropriate therapy (p = 0.009) in the standardised compared to the physician-led group. There was a non-significant 30 % risk reduction in appropriate therapy (p = 0.32). Results were consistent across primary and secondary prevention patients. There were no significant differences in the rates of syncope, hospitalisation, and death. In unselected patients in a real-world setting, introduction of a standardised programming protocol, using long detection times and high detection zones, significantly reduces the burden of ICD therapy without an increase in adverse outcomes.

Venetoclax plus rituximab in relapsed or refractory chronic lymphocytic leukaemia: a phase 1b study.

PubMed

Seymour, John F; Ma, Shuo; Brander, Danielle M; Choi, Michael Y; Barrientos, Jacqueline; Davids, Matthew S; Anderson, Mary Ann; Beaven, Anne W; Rosen, Steven T; Tam, Constantine S; Prine, Betty; Agarwal, Suresh K; Munasinghe, Wijith; Zhu, Ming; Lash, L Leanne; Desai, Monali; Cerri, Elisa; Verdugo, Maria; Kim, Su Young; Humerickhouse, Rod A; Gordon, Gary B; Kipps, Thomas J; Roberts, Andrew W

2017-02-01

Selective BCL2 inhibition with venetoclax has substantial activity in patients with relapsed or refractory chronic lymphocytic leukaemia. Combination therapy with rituximab enhanced activity in preclinical models. The aim of this study was to assess the safety, pharmacokinetics, and activity of venetoclax in combination with rituximab. Adult patients with relapsed or refractory chronic lymphocytic leukaemia (according to the 2008 Modified International Workshop on CLL guidelines) or small lymphocytic lymphoma were eligible for this phase 1b, dose-escalation trial. The primary outcomes were to assess the safety profile, to determine the maximum tolerated dose, and to establish the recommended phase 2 dose of venetoclax when given in combination with rituximab. Secondary outcomes were to assess the pharmacokinetic profile and analyse efficacy, including overall response, duration of response, and time to tumour progression. Minimal residual disease was a protocol-specified exploratory objective. Central review of the endpoints was not done. Venetoclax was dosed daily using a stepwise escalation to target doses (200-600 mg) and then monthly rituximab commenced (375 mg/m 2 in month 1 and 500 mg/m 2 in months 2-6). Adverse events were graded according to the National Cancer Institute Common Terminology Criteria for adverse events version 4.0. Protocol-guided drug cessation was allowed for patients who achieved complete response (including complete response with incomplete marrow recovery) or negative bone marrow minimal residual disease. Analyses were done per protocol for all patients who commenced drug and included all patients who received at least one dose of venetoclax. Data were pooled across dose cohorts. Patients are still receiving therapy and follow-up is ongoing. The trial is registered at ClinicalTrials.gov, number NCT01682616. Between Aug 6, 2012, and May 28, 2014, we enrolled 49 patients. Common grade 1-2 toxicities included upper respiratory tract infections (in 28 [57%] of 49 patients), diarrhoea (27 [55%]), and nausea (25 [51%]). Grade 3-4 adverse events occurred in 37 (76%) of 49 patients; most common were neutropenia (26 [53%]), thrombocytopenia (eight [16%]), anaemia (seven [14%]), febrile neutropenia (six [12%]), and leucopenia (six [12%]). The most common serious adverse events were pyrexia (six [12%]), febrile neutropenia (five [10%]), lower respiratory tract infection, and pneumonia (each three [6%]). Clinical tumour lysis syndrome occurred in two patients (resulting in one death) who initiated venetoclax at 50 mg. After enhancing tumour lysis syndrome prophylaxis measures and commencing venetoclax at 20 mg, clinical tumour lysis syndrome did not occur. The maximum tolerated dose was not identified; the recommended phase 2 dose of venetoclax in combination with rituximab was 400 mg. Overall, 42 (86%) of 49 patients achieved a response, including a complete response in 25 (51%) of 49 patients. 2 year estimates for progression-free survival and ongoing response were 82% (95% CI 66-91) and 89% (95% CI 72-96), respectively. Negative marrow minimal residual disease was attained in 20 (80%) of 25 complete responders and 28 (57%) of 49 patients overall. 13 responders ceased all therapy; among these all 11 minimal residual disease-negative responders remain progression-free off therapy. Two with minimal residual disease-positive complete response progressed after 24 months off therapy and re-attained response after re-initiation of venetoclax. A substantial proportion of patients achieved an overall response with the combination of venetoclax and rituximab including 25 (51%) of 49 patients who achieved a complete response and 28 (57%) of 49 patients who achieved negative marrow minimal residual disease with acceptable safety. The depth and durability of responses observed with the combination offers an attractive potential treatment option for patients with relapsed or refractory chronic lymphocytic leukaemia and could allow some patients to maintain response after discontinuing therapy, a strategy that warrants further investigation in randomised studies. AbbVie Inc and Genentech Inc. Copyright © 2017 Elsevier Ltd. All rights reserved.

Venetoclax plus rituximab in relapsed or refractory chronic lymphocytic leukaemia: a phase 1b study

PubMed Central

Seymour, John F; Ma, Shuo; Brander, Danielle M; Choi, Michael Y; Barrientos, Jacqueline; Davids, Matthew S; Anderson, Mary Ann; Beaven, Anne W; Rosen, Steven T; Tam, Constantine S; Prine, Betty; Agarwal, Suresh K; Munasinghe, Wijith; Zhu, Ming; Lash, L Leanne; Desai, Monali; Cerri, Elisa; Verdugo, Maria; Kim, Su Young; Humerickhouse, Rod A; Gordon, Gary B; Kipps, Thomas J; Roberts, Andrew W

2017-01-01

Summary Background Selective BCL2 inhibition with venetoclax has substantial activity in patients with relapsed or refractory chronic lymphocytic leukaemia. Combination therapy with rituximab enhanced activity in preclinical models. The aim of this study was to assess the safety, pharmacokinetics, and activity of venetoclax in combination with rituximab. Methods Adult patients with relapsed or refractory chronic lymphocytic leukaemia (according to the 2008 Modified International Workshop on CLL guidelines) or small lymphocytic lymphoma were eligible for this phase 1b, dose-escalation trial. The primary outcomes were to assess the safety profile, to determine the maximum tolerated dose, and to establish the recommended phase 2 dose of venetoclax when given in combination with rituximab. Secondary outcomes were to assess the pharmacokinetic profile and analyse efficacy, including overall response, duration of response, and time to tumour progression. Minimal residual disease was a protocol-specified exploratory objective. Central review of the endpoints was not done. Venetoclax was dosed daily using a stepwise escalation to target doses (200–600 mg) and then monthly rituximab commenced (375 mg/m2 in month 1 and 500 mg/m2 in months 2–6). Adverse events were graded according to the National Cancer Institute Common Terminology Criteria for adverse events version 4.0. Protocol-guided drug cessation was allowed for patients who achieved complete response (including complete response with incomplete marrow recovery) or negative bone marrow minimal residual disease. Analyses were done per protocol for all patients who commenced drug and included all patients who received at least one dose of venetoclax. Data were pooled across dose cohorts. Patients are still receiving therapy and follow-up is ongoing. The trial is registered at ClinicalTrials.gov, number NCT01682616. Findings Between Aug 6, 2012, and May 28, 2014, we enrolled 49 patients. Common grade 1–2 toxicities included upper respiratory tract infections (in 28 [57%] of 49 patients), diarrhoea (27 [55%]), and nausea (25 [51%]). Grade 3–4 adverse events occurred in 37 (76%) of 49 patients; most common were neutropenia (26 [53%]), thrombocytopenia (eight [16%]), anaemia (seven [14%]), febrile neutropenia (six [12%]), and leucopenia (six [12%]). The most common serious adverse events were pyrexia (six [12%]), febrile neutropenia (five [10%]), lower respiratory tract infection, and pneumonia (each three [6%]). Clinical tumour lysis syndrome occurred in two patients (resulting in one death) who initiated venetoclax at 50 mg. After enhancing tumour lysis syndrome prophylaxis measures and commencing venetoclax at 20 mg, clinical tumour lysis syndrome did not occur. The maximum tolerated dose was not identified; the recommended phase 2 dose of venetoclax in combination with rituximab was 400 mg. Overall, 42 (86%) of 49 patients achieved a response, including a complete response in 25 (51%) of 49 patients. 2 year estimates for progression-free survival and ongoing response were 82% (95% CI 66–91) and 89% (95% CI 72–96), respectively. Negative marrow minimal residual disease was attained in 20 (80%) of 25 complete responders and 28 (57%) of 49 patients overall. 13 responders ceased all therapy; among these all 11 minimal residual disease-negative responders remain progression-free off therapy. Two with minimal residual disease-positive complete response progressed after 24 months off therapy and re-attained response after re-initiation of venetoclax. Interpretation A substantial proportion of patients achieved an overall response with the combination of venetoclax and rituximab including 25 (51%) of 49 patients who achieved a complete response and 28 (57%) of 49 patients who achieved negative marrow minimal residual disease with acceptable safety. The depth and durability of responses observed with the combination offers an attractive potential treatment option for patients with relapsed or refractory chronic lymphocytic leukaemia and could allow some patients to maintain response after discontinuing therapy, a strategy that warrants further investigation in randomised studies. PMID:28089635

Infusing CD19-directed T cells to augment disease control in patients undergoing autologous hematopoietic stem-cell transplantation for advanced B-lymphoid malignancies.

PubMed

Kebriaei, Partow; Huls, Helen; Jena, Bipulendu; Munsell, Mark; Jackson, Rineka; Lee, Dean A; Hackett, Perry B; Rondon, Gabriela; Shpall, Elizabeth; Champlin, Richard E; Cooper, Laurence J N

2012-05-01

Limited curative treatment options exist for patients with advanced B-lymphoid malignancies, and new therapeutic approaches are needed to augment the efficacy of hematopoietic stem-cell transplantation (HSCT). Cellular therapies, such as adoptive transfer of T cells that are being evaluated to target malignant disease, use mechanisms independent of chemo- and radiotherapy with nonoverlapping toxicities. Gene therapy is employed to generate tumor-specific T cells, as specificity can be redirected through enforced expression of a chimeric antigen receptor (CAR) to achieve antigen recognition based on the specificity of a monoclonal antibody. By combining cell and gene therapies, we have opened a new Phase I protocol at the MD Anderson Cancer Center (Houston, TX) to examine the safety and feasibility of administering autologous genetically modified T cells expressing a CD19-specific CAR (capable of signaling through chimeric CD28 and CD3-ζ) into patients with high-risk B-lymphoid malignancies undergoing autologous HSCT. The T cells are genetically modified by nonviral gene transfer of the Sleeping Beauty system and CAR(+) T cells selectively propagated in a CAR-dependent manner on designer artificial antigen-presenting cells. The results of this study will lay the foundation for future protocols including CAR(+) T-cell infusions derived from allogeneic sources.

Predictive model for photodynamic therapy with gold nanoparticles as vehicle for the photosensitizer delivery

NASA Astrophysics Data System (ADS)

Salas-García, I.; Fanjul-Vélez, F.; Ortega-Quijano, N.; Arce-Diego, J. L.

2013-06-01

Photodynamic Therapy offers multiple advantages to treat nonmelanoma skin cancer compared to conventional treatment techniques such as surgery, radiotherapy or chemotherapy. Among these advantages are particularly relevant its noninvasive nature, the use of non ionizing radiation and its high selectivity. However the therapeutic efficiency of the current clinical protocol is not complete in all the patients and depends on the type of pathology. Emerging strategies to overcome its current shortcomings include the use of nanostructures that can act as carriers for conventional photosensitizers and improve the treatment selectivity and provide a controlled release of the photoactive agent. In this work, a model for photodynamic therapy combined with gold nanocarriers for a photosensitizer commonly used in dermatology is presented and applied to a basal cell carcinoma in order to predict the cytotoxic agent spatial and temporal evolution.

Reverse amblyopia with atropine treatment.

PubMed

Hainline, Bryan C; Sprunger, Derek C; Plager, David A; Neely, Daniel E; Guess, Matthew G

2009-01-01

Occlusion, pharmacologic pernalization and combined therapy have been documented in controlled studies to effectively treat amblyopia with few complications. However, there remain concerns about the effectiveness and complications when, as in this case, there are not standardized treatment protocols. A retrospective chart review of 133 consecutive patients in one community based ophthalmology practice treated for amblyopia was performed. Treatments evaluated were occlusion only, atropine penalization, and combination of occlusion and atropine. Reverse amblyopia was defined as having occured when the visual acuity of the sound eye was 3 LogMar units worse than visual acuity of the amblyopia eye after treatment. Improvement in vision after 6 months and 1 year of amblyopia therapy was similar among all three groups: 0.26 LogMar lines and 0.30 in the atropine group, 0.32 and 0.34 in the occlusion group, and 0.24 and 0.32 in the combined group. Eight (6%) patients demonstrated reverse amblyopia. The mean age of those who developed reverse amblyopia was 3.5 years, 1.5 years younger than the mean age of the study population, 7/8 had strabismic amblyopia, 6/8 were on daily atropine and had a mean refractive error of +4.77 diopters in the amblyopic eye and +5.06 diopters in the sound eye. Reverse amblyopia did not occur with occlusion only therapy. In this community based ophthalmology practice, atropine, patching, and combination therapy appear to be equally effective modalities to treat ambyopia. Highly hyperopic patients under 4 years of age with dense, strabismic amblyopia and on daily atropine appeared to be most at risk for development of reverse amblyopia.

Randomized phase II--study evaluating EGFR targeting therapy with cetuximab in combination with radiotherapy and chemotherapy for patients with locally advanced pancreatic cancer--PARC: study protocol [ISRCTN56652283].

PubMed

Krempien, R; Muenter, M W; Huber, P E; Nill, S; Friess, H; Timke, C; Didinger, B; Buechler, P; Heeger, S; Herfarth, K K; Abdollahi, A; Buchler, M W; Debus, J

2005-10-11

Pancreatic cancer is the fourth commonest cause of death from cancer in men and women. Advantages in surgical techniques, radiation therapy techniques, chemotherapeutic regimes, and different combined-modality approaches have yielded only a modest impact on the prognosis of patients with pancreatic cancer. Thus there is clearly a need for additional strategies. One approach involves using the identification of a number of molecular targets that may be responsible for the resistance of cancer cells to radiation or to other cytotoxic agents. As such, these molecular determinants may serve as targets for augmentation of the radiotherapy or chemotherapy response. Of these, the epidermal growth factor receptor (EGFR) has been a molecular target of considerable interest and investigation, and there has been a tremendous surge of interest in pursuing targeted therapy of cancers via inhibition of the EGFR. The PARC study is designed as an open, controlled, prospective, randomized phase II trial. Patients in study arm A will be treated with chemoradiation using intensity modulated radiation therapy (IMRT) combined with gemcitabine and simultaneous cetuximab infusions. After chemoradiation the patients receive gemcitabine infusions weekly over 4 weeks. Patients in study arm B will be treated with chemoradiation using intensity modulated radiation therapy (IMRT) combined with gemcitabine and simultaneous cetuximab infusions. After chemoradiation the patients receive gemcitabine weekly over 4 weeks and cetuximab infusions over 12 weeks. A total of 66 patients with locally advanced adenocarcinoma of the pancreas will be enrolled. An interim analysis for patient safety reasons will be done one year after start of recruitment. Evaluation of the primary endpoint will be performed two years after the last patient's enrollment. The primary objective of this study is to evaluate the feasibility and the toxicity profile of trimodal therapy in pancreatic adenocarcinoma with chemoradiation therapy with gemcitabine and intensity modulated radiation therapy (IMRT) and EGFR-targeted therapy using cetuximab and to compare between two different methods of cetuximab treatment schedules (concomitant versus concomitant and sequential cetuximab treatment). Secondary objectives are to determine the role and the mechanism of cetuximab in patient's chemoradiation regimen, the response rate, the potential of this combined modality treatment to concert locally advanced lesions to potentially resectable lesions, the time to progression interval and the quality of life.

Efficacy and Safety of Switching Prostaglandin Analog Monotherapy to Tafluprost/Timolol Fixed-Combination Therapy

PubMed Central

Kitamura, Kazuyoshi; Chiba, Tatsuya; Mabuchi, Fumihiko; Ishijima, Kiyotaka; Omoto, Shu; Kashiwagi, Fumiko; Godo, Takashi; Kogure, Satoshi; Goto, Teruhiko; Shibuya, Takashi; Tanabe, Jhoji; Tsukahara, Shigeo; Tsuchiya, Tadaharu; Tokunaga, Takaharu; Hosaka, Osamu; Saito, Tetsunori

2018-01-01

Purpose To assess the efficacy and safety of switching from prostaglandin analog (PGA) monotherapy to tafluprost/timolol fixed-combination (Taf/Tim) therapy. Subjects and Methods Patients with primary open-angle glaucoma, normal-tension glaucoma, or ocular hypertension who had received PGA monotherapy for at least 3 months were enrolled. Patients were examined at 1, 2, and 3 months after changing therapies. Subsequently, the patients were returned to PGA monotherapy. The examined parameters included intraocular pressure (IOP) and adverse events. A questionnaire survey was conducted after the switch to Taf/Tim therapy. Results Forty patients with a mean age of 66.5 ± 10.3 years were enrolled; 39 of these patients completed the study protocol. Switching to Taf/Tim significantly reduced the IOP from 18.2 ± 2.6 mmHg at baseline to 14.8 ± 2.5 mmHg at 1 month, 15.2 ± 2.8 mmHg at 2 months, and 14.9 ± 2.5 mmHg at 3 months (P < 0.001). Switching back to the original PGA monotherapy returned the IOP values to baseline levels. Taf/Tim reduced the pulse rate insignificantly. No significant differences were observed in blood pressure, conjunctival hyperemia, or corneal adverse events. A questionnaire showed that the introduction of Taf/Tim did not significantly influence symptoms. Conclusions Compared with PGA monotherapy, Taf/Tim fixed-combination therapy significantly reduced IOP without severe adverse events. PMID:29675274

Photodynamic therapy as a local therapeutic adjunct for the treatment of vertebral metastases

NASA Astrophysics Data System (ADS)

Yee, Albert; Burch, Shane; Akens, Margarete; Won, Emily; Lo, Victor; Wise-Milestone, Lisa; Bisland, Stuart; Theriault, Aimee; Niu, Carolyn; Wilson, Brian C.; Whyne, Cari

2013-03-01

Metastatic cancer causes the majority of tumors in bone, most frequently detected in the spinal column. Skeletal complications cause pain and neurologic impairment. Photodynamic therapy (PDT) has been used to treat a variety of cancers. Minimally invasive surgical (MIS) strategies may allow targeted light application essential for PDT within bone structures. The purpose of this manuscript is to provide an update on pre-clinical status as well as early clinical experience of a Phase I clinical trial on vertebral PDT. A pre-clinical (rnu/rnu rat) vertebral metastasis model of osteolytic (MT-1 breast cancer) was optimized and used to evaluate the effect of vertebral PDT. PDT alone and in combination with other standard local (radiation therapy, RT) and systemic (bisphosphonates, BP) therapies was evaluated through bioluminescence imaging, micro-CT based stereology, histology, and biomechanical testing. Single PDT treatment (photosensitizer BPD-MA, 690nm light) ablated tumor tissue in targeted vertebrae. PDT led to significant increases in bone structural properties, with greatest benefits observed from combined BP+PDT therapy: 76% and 19% increases in bone volume fraction in treated tumor-bearing and healthy untreated controls, respectively. Similar synergistic improvements (but of lesser magnitude) were found in combined PDT+RT treatments. The safety and feasibility of MIS+PDT were evaluated in scale-up animal studies, refining surgical technique for clinical translation. Following appropriate institutional review board as well as Health Canada approval, 5 patients (light only control group) have undergone protocoled treatment to date. These patients have guided further refinement of human therapeutic application from a laser delivery and vertebral bone access perspective.

Recolonization of the oral cavity by Streptococcus mutans after a combined mechanical/chemical antisepsis protocol.

PubMed

Farina, R; Squarzoni, M A; Calura, G; Trombelli, L

2009-06-01

The bacterial colonization of teeth by Streptococcus mutans (StrepM) represents a major risk factor for the development of dental caries. At present, no clinical studies have explored the effect of a combined mechanical-chemical antisepsis protocol in a periodontally-healthy population and the pattern of recolonization of StrepM in subjects whose StrepM infection was successfully eradicated. The present study was designed in order to 1) determine the salivary and plaque changes in StrepM content after a combined mechanical/chemical antisepsis protocol; and 2) evaluate the pattern of recolonization when StrepM was successfully eradicated from saliva and plaque. Thirty-five periodontally-healthy and caries-susceptible subjects successfully entered and concluded the study. At baseline, non-surgical periodontal therapy was performed according to the principles of full mouth disinfection. Adjunctive home-based rinsing with a 0.2% chlorhexidine mouthrinse was requested for the following week. StrepM concentration was assessed in saliva and plaque at the initial contact appointment, at baseline, and 1-week, 1-month, 3-month and 6-month follow-up. A significant effect of ''time'' on StrepM concentration in saliva and plaque was observed (P<0.000). In subjects with successful eradication of StrepM at 1 week (N=17 plaque samples), StrepM infection recurrence occurred within 3-6 months. The results of the present study demonstrated that 1) the application of the investigated mechanical/chemical antisepsis protocol can effectively reduce StrepM colonies in saliva and plaque of periodontally healthy subjects; and 2) in plaque samples, StrepM infection recurrence tends to occur within 3-6 months.

Fractional Er:YAG laser assisting topical betamethasone solution in combination with NB-UVB for resistant non-segmental vitiligo.

PubMed

Yan, Ru; Yuan, Jinping; Chen, Hongqiang; Li, Yuan-Hong; Wu, Yan; Gao, Xing-Hua; Chen, Hong-Duo

2017-09-01

Resistant non-segmental vitiligo is difficult to be treated. Ablative erbium-YAG (Er:YAG) laser has been used in the treatment of vitiligo, but the ablation of entire epidermis frustrated the compliance of patients. The purpose of this study is to investigate the effects of fractional Er:YAG laser followed by topical betamethasone and narrow band ultraviolet B (NB-UVB) therapy in the treatment of resistant non-segmental vitiligo. The vitiligo lesions of each enrolled patient were divided into four treatment parts, which were all irradiated with NB-UVB. Three parts were, respectively, treated with low, medium, or high energy of Er:YAG laser, followed by topical betamethasone solution application. A control part was spared with laser treatment and topical betamethasone. The treatment period lasted 6 months. The efficacy was assessed by two blinded dermatologists. Treatment protocol with high energy of 1800 mJ/P of fractional Er:YAG laser followed by topical betamethasone solution and in combination with NB-UVB made 60% patients achieve marked to excellent improvement in white patches. The protocol with medium energy of 1200 mJ/P of laser assisted approximate 36% patients achieve such improvement. The two protocols, respectively, showed better efficacies than NB-UVB only protocol. However, fractional Er:YAG laser at low energy of 600 mJ/P did not provide such contributions to the treatment of vitiligo. The fractional Er:YAG laser in combination with topical betamethasone solution and NB-UVB was suitable for resistant non-segmental vitiligo. The energy of laser was preferred to be set at relatively high level.

Preservation of renal function during maintenance therapy with cyclosporine.

PubMed

Serón, D; Moreso, F

2004-03-01

During the last 20 years the management of cyclosporine (CsA) has improved due to the introduction of microemulsion technology, C2 monitoring, and combination with other new immunosuppressants. All these modifications have reduced the incidence of biopsy-proven acute rejection episodes to approximately 10%. However despite the wide experience, there are unanswered questions regarding CsA monitoring after the first year. Available clinical and histological data suggest that the therapeutic range to avoid nephrotoxicity or underimmunosuppression during the maintenance period is rather narrow. Furthermore, the combination of CsA with new immunosuppressants may modify the target CsA levels. Although the utility of C2 levels during the first year has been well characterized, there are few data on its utility for maintenance therapy, particularly the therapeutic range for C2 levels in patients receiving different immunosuppressive combinations. Since serum creatinine does not precisely reflect the progression of chronic allograft nephropathy, the efficacy of C2 monitoring during the maintenance period must be assessed not only by means of evaluation of renal function, but also histologic assessment using protocol biopsies.

Patients' and therapists' experiences with a new treatment programme for eating disorders that combines physical exercise and dietary therapy: the PED-t trial. A qualitative study protocol.

PubMed

Pettersen, Gunn; Rosenvinge, Jan H; Bakland, Maria; Wynn, Rolf; Mathisen, Therese Fostervold; Sundgot-Borgen, Jorunn

2018-01-08

Women with bulimia nervosa and binge eating disorder often suffer for many years before they seek professional help. Evidence-based treatments like cognitive-behavioural therapy (CBT) might be poorly accessible, and about 50% of those who receive CBT respond to it. Such outcome may reflect the heterogeneous nature of eating disorders, and addressing this heterogeneity calls for expanding the portfolio of treatment options. In particular, it is important to explore such options' acceptability, tolerability and affordability expressed through experiences with the treatment. This protocol outlines the rationale and design of a qualitative study. It captures experiences from patients and therapists who were involved in a randomised controlled trial (RCT) exploring the efficacy of a new group-based treatment programme combining physical exercise and dietary therapy. 15 patients with bulimia nervosa or binge eating disorder, 10 therapists (physical trainers and dietitians) and 6-10 patients who dropped out of the RCT will be semistructurally interviewed. All interviews will be analysed using a systematic text condensation approach. Results will be presented in peer-reviewed international journals, and at relevant international conferences. Key findings will be available to study participants as well as to patient organisations and health authorities. The overall study meets the intent and requirements of the Health Research Act and the Declaration of Helsinki. It is approved by the regional committee for medical research ethics (2013/1871). NCT02079935; Pre-results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Incidence of bisphosphonate-related osteonecrosis of the jaw in high-risk patients undergoing surgical tooth extraction.

PubMed

Bodem, Jens Philipp; Kargus, Steffen; Eckstein, Stefanie; Saure, Daniel; Engel, Michael; Hoffmann, Jürgen; Freudlsperger, Christian

2015-05-01

As the most suitable approach for preventing bisphosphonate-related osteonecrosis of the jaw (BRONJ) in patients undergoing surgical tooth extraction is still under discussion, the present study evaluates the incidence of BRONJ after surgical tooth extraction using a standardized surgical protocol in combination with an adjuvant perioperative treatment setting in patients who are at high-risk for developing BRONJ. High-risk patients were defined as patients who received intravenous bisphosphonate (BP) due to a malignant disease. All teeth were removed using a standardized surgical protocol. The perioperative adjuvant treatment included intravenous antibiotic prophylaxis starting at least 24 h before surgery, a gastric feeding tube and mouth rinses with chlorhexidine (0.12%) three times a day. In the follow-up period patients were examined every 4 weeks for the development of BRONJ. Minimum follow-up was 12 weeks. In 61 patients a total number of 184 teeth were removed from 102 separate extraction sites. In eight patients (13.1%) BRONJ developed during the follow-up. A higher risk for developing BRONJ was found in patients where an additional osteotomy was necessary (21.4% vs. 8.0%; p = 0.0577), especially for an osteotomy of the mandible (33.3% vs. 7.3%; p = 0.0268). Parameters including duration of intravenous antibiotic prophylaxis, the use of a gastric feeding tube and the duration of intravenous BP therapy showed no statistical impact on the development of BRONJ. Furthermore, patients currently undergoing intravenous BP therapy showed no higher risk for BRONJ compared with patients who have paused or completed their intravenous BP therapy (p = 0.4232). This study presents a protocol for surgical tooth extraction in high-risk BP patients in combination with a perioperative adjuvant treatment setting, which reduced the risk for postoperative BRONJ to a minimum. However, the risk for BRONJ increases significantly if an additional osteotomy is necessary, especially in the mandible. Copyright © 2015 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

All-trans retinoic acid/As2O3 combination yields a high quality remission and survival in newly diagnosed acute promyelocytic leukemia

PubMed Central

Shen, Zhi-Xiang; Shi, Zhan-Zhong; Fang, Jing; Gu, Bai-Wei; Li, Jun-Min; Zhu, Yong-Mei; Shi, Jing-Yi; Zheng, Pei-Zheng; Yan, Hua; Liu, Yuan-Fang; Chen, Yu; Shen, Yang; Wu, Wen; Tang, Wei; Waxman, Samuel; de Thé, Hugues; Wang, Zhen-Yi; Chen, Sai-Juan; Chen, Zhu

2004-01-01

Both all-trans retinoic acid (ATRA) and arsenic trioxide (As2O3) have proven to be very effective in obtaining high clinical complete remission (CR) rates in acute promyelocytic leukemia (APL), but they had not been used jointly in an integrated treatment protocol for remission induction or maintenance among newly diagnosed APL patients. In this study, 61 newly diagnosed APL subjects were randomized into three treatment groups, namely by ATRA, As2O3, and the combination of the two drugs. CR was determined by hematological analysis, tumor burden was examined with real-time quantitative RT-PCR of the PML-RARα (promyelocytic leukemia-retinoic acid receptor α) fusion transcripts, and side effects were evaluated by means of clinical examinations. Mechanisms possibly involved were also investigated with cellular and molecular biology methods. Although CR rates in three groups were all high (≥90%), the time to achieve CR differed significantly, with that of the combination group being the shortest one. Earlier recovery of platelet count was also found in this group. The disease burden as reflected by fold change of PML-RARα transcripts at CR decreased more significantly in combined therapy as compared with ATRA or As2O3 mono-therapy (P < 0.01). This difference persisted after consolidation (P < 0.05). Importantly, all 20 cases in the combination group remained in CR whereas 7 of 37 cases treated with mono-therapy relapsed (P < 0.05) after a follow-up of 8–30 months (median: 18 months). Synergism of ATRA and As2O3 on apoptosis and degradation of PML-RARα oncoprotein might provide a plausible explanation for superior efficacy of combinative therapy in clinic. In conclusion, the ATRA/As2O3 combination for remission/maintenance therapy of APL brings much better results than either of the two drugs used alone in terms of the quality of CR and the status of the disease-free survival. PMID:15044693

Gold Nanostructures as a Platform for Combinational Therapy in Future Cancer Therapeutics

PubMed Central

Jelveh, Salomeh; Chithrani, Devika B.

2011-01-01

The field of nanotechnology is currently undergoing explosive development on many fronts. The technology is expected to generate innovations and play a critical role in cancer therapeutics. Among other nanoparticle (NP) systems, there has been tremendous progress made in the use of spherical gold NPs (GNPs), gold nanorods (GNRs), gold nanoshells (GNSs) and gold nanocages (GNCs) in cancer therapeutics. In treating cancer, radiation therapy and chemotherapy remain the most widely used treatment options and recent developments in cancer research show that the incorporation of gold nanostructures into these protocols has enhanced tumor cell killing. These nanostructures further provide strategies for better loading, targeting, and controlling the release of drugs to minimize the side effects of highly toxic anticancer drugs used in chemotherapy and photodynamic therapy. In addition, the heat generation capability of gold nanostructures upon exposure to UV or near infrared light is being used to damage tumor cells locally in photothermal therapy. Hence, gold nanostructures provide a versatile platform to integrate many therapeutic options leading to effective combinational therapy in the fight against cancer. In this review article, the recent progress in the development of gold-based NPs towards improved therapeutics will be discussed. A multifunctional platform based on gold nanostructures with targeting ligands, therapeutic molecules, and imaging contrast agents, holds an array of promising directions for cancer research. PMID:24212654

Relationship between initial therapy and blood pressure control for high-risk hypertension patients in the UK: a retrospective cohort study from the THIN general practice database.

PubMed

Weir, Sharada; Juhasz, Attila; Puelles, Jorge; Tierney, Travis S

2017-07-28

To examine the UK practice patterns in treating newly diagnosed hypertension and to determine whether subgroups of high-risk patients are more or less likely to follow particular therapeutic protocols and to reach blood pressure goals. Retrospective cohort study. This study examined adults in The Health Improvement Network (THIN) UK general practice medical records database who were initiated on medication for hypertension. 48 131 patients with essential hypertension diagnosed between 2008 and 2010 who were registered with a participating practice for a minimum of 13 months prior to, and 6 months following, initiation of therapy. We excluded patients with gestational hypertension or secondary hypertension. Patients were classified into risk groups based on blood pressure readings and comorbid conditions. Odds of receiving single versus fixed or free-drug combination therapy and odds of achieving blood pressure control were assessed using multivariable logistic regression. The vast majority of patients (95.8%) were initiated on single drug therapy. Patients with high cardiovascular risk (patients with grade 2-3 hypertension or those with high normal/grade 1 hypertension plus at least one cardiovascular condition pretreatment) had a statistically significant benefit of starting immediately on combination therapy when blood pressure control was the desired goal (OR: 1.23; 95% CI: 1.06 to 1.42) but, surprisingly, were less likely than patients with no risk factors to receive combination therapy (OR: 0.53; 95% CI: 0.47 to 0.59). Our results suggest that combination therapy may be indicated for patients with high cardiovascular risk, who accounted for 60.6% of our study population. The National Institute for Health and Care Excellence guideline CG34 of 2006 (in effect during the study period) recommended starting with single drug class therapy for most patients, and this advice does seem to have been followed even in cases where a more aggressive approach might have been considered. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

The Effect of Entonox, Play Therapy and a Combination on Pain Relief in Children: A Randomized Controlled Trial.

PubMed

Mohan, Simi; Nayak, Ruma; Thomas, Reju Joseph; Ravindran, Vinitha

2015-12-01

Pediatric pain is often undertreated/neglected due to time constraints, difficulties in timing of oral analgesics, fear of side effects of opioids and anxiolytics, and apprehension of additional pain in the use of local anesthetic injections. In this study, the researcher was prompted to choose rapidly acting interventions that were low dose and allowed the child to stay alert, suitable for a quick discharge. The purpose of this study was to evaluate the effects of Entonox, play therapy, and a combination to relieve procedural pain in children aged 4-15 years. The study was designed as a randomized controlled trial; the subjects were divided into four groups using a sequential allocation plan from 123 total subjects. Group A received Entonox, Group B received play therapy, Group C received both Entonox and play therapy, and Group D received existing standard interventions. The study was vetted by the departmental study review committee. The pain level was assessed using FLACC scale for children aged 4-9 years and the Wong Bakers Faces Pain Scale for children aged 10-15 years; scores ranged from 0 to 10. All the data were analyzed using SPSS 16.0 with descriptive statistics and, inferential statistics. The mean pain scores were as follows: Entonox group, 2.87; Play therapy group, 4; combination group, 3; and control group, 5.87. When statistical testing was applied, a significant reduction in the pain score in all the three experimental groups when compared to the control group was found (p = .002), but not in the pain score among the three experimental groups (p = .350). The findings of this study indicated that all three interventions were effective in lowering pain scores when compared to the control group. Play therapy is as potent as Entonox in relieving procedural pain, though there was no additive effect on pain relief when play therapy and Entonox were combined. A protocol for age-related choice between play therapy and Entonox administration was introduced as a standing order in the Pediatric Surgery department for acute procedural pain relief. Copyright © 2015 American Society for Pain Management Nursing. Published by Elsevier Inc. All rights reserved.

Ovarian Damage in Young Premenopausal Women Undergoing Chemotherapy for Cancer

ClinicalTrials.gov

2012-03-16

Leukemia; Long-term Effects Secondary to Cancer Therapy in Adults; Long-term Effects Secondary to Cancer Therapy in Children; Lymphoma; Sexual Dysfunction and Infertility; Sexuality and Reproductive Issues; Unspecified Adult Solid Tumor, Protocol Specific; Unspecified Childhood Solid Tumor, Protocol Specific

Positioning Vascularized Composite Allotransplantation in the Spectrum of Transplantation

DTIC Science & Technology

2017-10-01

have now shown that the efficacy of both protocols is dependent upon a radiation-sensitive donor bone marrow (BM) cell type that is of T or B cell... dependent VCA survival. IL-2C Therapy Increases the Number but Not Function of Foxp3 CD4+ Treg Cells To test the effects of JES6-1 mAb-based IL-2C...which Treg cell- dependent immunoregulation has considerable potential. These IL-2C studies are now “in press” (4). TASK 5: OPTIMAL COMBINATION

Red light photodynamic therapy for actinic keratosis using 37 J/cm2 : Fractionated irradiation with 12.3 mW/cm2 after 30 minutes incubation time compared to standard continuous irradiation with 75 mW/cm2 after 3 hours incubation time using a mathematical modeling.

PubMed

Vignion-Dewalle, Anne-Sophie; Baert, Gregory; Devos, Laura; Thecua, Elise; Vicentini, Claire; Mortier, Laurent; Mordon, Serge

2017-09-01

Photodynamic therapy (PDT) is an emerging treatment modality for various diseases, especially for dermatological conditions. Although, the standard PDT protocol for the treatment of actinic keratoses in Europe has shown to be effective, treatment-associated pain is often observed in patients. Different modifications to this protocol attempted to decrease pain have been investigated. The decrease in fluence rate seems to be a promising solution. Moreover, it has been suggested that light fractionation significantly increases the efficacy of PDT. Based on a flexible light-emitting textile, the FLEXITHERALIGHT device specifically provides a fractionated illumination at a fluence rate more than six times lower than that of the standard protocol. In a recently completed clinical trial of PDT for the treatment of actinic keratosis, the non-inferiority of a protocol involving illumination with the FLEXITHERALIGHT device after a short incubation time and referred to as the FLEXITHERALIGHT protocol has been assessed compared to the standard protocol. In this paper, we propose a comparison of the two above mentioned 635 nm red light protocols with 37 J/cm 2 in the PDT treatment of actinic keratosis: the standard protocol and the FLEXITHERALIGHT one through a mathematical modeling. This mathematical modeling, which slightly differs from the one we have already published, enables the local damage induced by the therapy to be estimated. The comparison performed in terms of the local damage induced by the therapy demonstrates that the FLEXITHERALIGHT protocol with lower fluence rate, light fractionation and shorter incubation time is somewhat less efficient than the standard protocol. Nevertheless, from the clinical trial results, the FLEXITHERALIGHT protocol results in non-inferior response rates compared to the standard protocol. This finding raises the question of whether the PDT local damage achieved by the FLEXITHERALIGHT protocol (respectively, the standard protocol) is sufficient (respectively, excessive) to destroy actinic keratosis cells. Lasers Surg. Med. 49:686-697, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Chronic idiopathic anal pain. Results of a diagnostic-therapeutic protocol in a colorectal referral unit.

PubMed

Armañanzas, Laura; Arroyo, Antonio; Ruiz-Tovar, Jaime; López, Alberto; Santos, Jair; Moya, Pedro; Gómez, María Amparo; Candela, Fernando; Calpena, Rafael

2015-01-01

Chronic idiopathic anal pain (CIAP) remains a diagnosis of exclusion. Its study and management still lack a standardized protocol. The aim of this study is to evaluate the results obtained with the diagnostic-therapeutic protocol established in our service. We performed a retrospective study of patients diagnosed with CIAP at the Colorectal Unit of the General University Hospital of Elche, between 2005 and 2011. We evaluated 57 patients with a diagnosis of chronic anal pain for functional anorectal disease (FAD). After the application of our diagnostic protocol, final diagnosis of chronic anal pain (CAP) was achieved in 43 cases (75%), including 22 cases of descending perineum syndrome, 12 of proctalgia fugax, 2 of pudendal neuritis and 7 of coccydynia. In 14 patients exclusion diagnosis of CIAP was established. Among the therapies used on patients with CIAP, biofeedback combined with conservative measures improved symptoms in 43% of the cases. Sacral nerve stimulation was assessed in patients who did not respond to other treatments. Through proper anamnesis, physical examination and complementary tests, a specific diagnosis of the cause of CAP by FAD can be achieved, reducing exclusion diagnosis of CIAP to 25% of cases. Conservative measures combined with biofeedback achieved an improvement in pain in more than 40% of the cases of CIAP in our study. Sacral nerve stimulation can be considered as a treatment option in refractory cases. Copyright © 2013 AEC. Publicado por Elsevier España, S.L.U. All rights reserved.

Immunosuppressive therapy in glomerular diseases: major accomplishment of Tadeusz Orłowski and his school.

PubMed

Smogorzewski, Mirosław J; Lao, Mieczysław; Gradowska, Liliana; Rowińska, Danuta; Rancewicz, Zofia

2009-05-01

Glomerulopathies are the third most common cause of end-stage renal failure. Immunosuppressive treatment of glomerulonephritis in a systematic way was introduced in Poland by Professor Tadeusz Orłowski in the early 1960s. The studies were conducted at the First Department of Medicine and at the Transplantation Institute of the Medical Academy in Warsaw in the years 1962-1988. This paper critically reviews the results of studies on the use of combined, triple-drug (prednisone/chlorambucil/azathioprine), immunosuppressive protocol in various pathological forms of glomerulopathies. We conclude that immunosuppressive protocols pioneered by Tadeusz Orłowski continue to be the backbone of the treatment of glomerulonephritis, especially the one with nephrotic syndrome, progressive impairment of kidney function and poor prognosis.

Cytoreductive conditioning intensity predicts clonal diversity in ADA-SCID retroviral gene therapy patients

PubMed Central

Lill, Georgia R.; Shaw, Kit; Carbonaro-Sarracino, Denise A.; Davila, Alejandra; Sokolic, Robert; Candotti, Fabio; Pellegrini, Matteo

2017-01-01

Retroviral gene therapy has proved efficacious for multiple genetic diseases of the hematopoietic system, but roughly half of clinical gene therapy trial protocols using gammaretroviral vectors have reported leukemias in some of the patients treated. In dramatic contrast, 39 adenosine deaminase–deficient severe combined immunodeficiency (ADA-SCID) patients have been treated with 4 distinct gammaretroviral vectors without oncogenic consequence. We investigated clonal dynamics and diversity in a cohort of 15 ADA-SCID children treated with gammaretroviral vectors and found clear evidence of genotoxicity, indicated by numerous common integration sites near proto-oncogenes and by increased abundance of clones with integrations near MECOM and LMO2. These clones showed stable behavior over multiple years and never expanded to the point of dominance or dysplasia. One patient developed a benign clonal dominance that could not be attributed to insertional mutagenesis and instead likely resulted from expansion of a transduced natural killer clone in response to chronic Epstein-Barr virus viremia. Clonal diversity and T-cell repertoire, measured by vector integration site sequencing and T-cell receptor β-chain rearrangement sequencing, correlated significantly with the amount of busulfan preconditioning delivered to patients and to CD34+ cell dose. These data, in combination with results of other ADA-SCID gene therapy trials, suggest that disease background may be a crucial factor in leukemogenic potential of retroviral gene therapy and underscore the importance of cytoreductive conditioning in this type of gene therapy approach. PMID:28351939

Cytoreductive conditioning intensity predicts clonal diversity in ADA-SCID retroviral gene therapy patients.

PubMed

Cooper, Aaron R; Lill, Georgia R; Shaw, Kit; Carbonaro-Sarracino, Denise A; Davila, Alejandra; Sokolic, Robert; Candotti, Fabio; Pellegrini, Matteo; Kohn, Donald B

2017-05-11

Retroviral gene therapy has proved efficacious for multiple genetic diseases of the hematopoietic system, but roughly half of clinical gene therapy trial protocols using gammaretroviral vectors have reported leukemias in some of the patients treated. In dramatic contrast, 39 adenosine deaminase-deficient severe combined immunodeficiency (ADA-SCID) patients have been treated with 4 distinct gammaretroviral vectors without oncogenic consequence. We investigated clonal dynamics and diversity in a cohort of 15 ADA-SCID children treated with gammaretroviral vectors and found clear evidence of genotoxicity, indicated by numerous common integration sites near proto-oncogenes and by increased abundance of clones with integrations near MECOM and LMO2 These clones showed stable behavior over multiple years and never expanded to the point of dominance or dysplasia. One patient developed a benign clonal dominance that could not be attributed to insertional mutagenesis and instead likely resulted from expansion of a transduced natural killer clone in response to chronic Epstein-Barr virus viremia. Clonal diversity and T-cell repertoire, measured by vector integration site sequencing and T-cell receptor β-chain rearrangement sequencing, correlated significantly with the amount of busulfan preconditioning delivered to patients and to CD34 + cell dose. These data, in combination with results of other ADA-SCID gene therapy trials, suggest that disease background may be a crucial factor in leukemogenic potential of retroviral gene therapy and underscore the importance of cytoreductive conditioning in this type of gene therapy approach.

Modulating chromatin structure and DNA accessibility by deacetylase inhibition enhances the anti-cancer activity of silver nanoparticles.

PubMed

Igaz, Nóra; Kovács, Dávid; Rázga, Zsolt; Kónya, Zoltán; Boros, Imre M; Kiricsi, Mónika

2016-10-01

Histone deacetylase (HDAC) inhibitors are considered as novel therapeutic agents inducing cell cycle arrest and apoptotic cell death in various cancer cells. Inhibition of deacetylase activity results in a relaxed chromatin structure thereby rendering the genetic material more vulnerable to DNA targeting agents that could be exploited by combinational cancer therapy. The unique potential of silver nanoparticles (AgNPs) in tumor therapy relies on the generation of reactive radicals which trigger oxidative stress, DNA damage and apoptosis in cancer cells. The revolutionary application of AgNPs as chemotherapeutical drugs seems very promising, nevertheless the exact molecular mechanisms of AgNP action in combination with other anti-cancer agents have yet to be elucidated in details before clinical administrations. As a step towards this we investigated the combinational effect of HDAC inhibition and AgNP administration in HeLa cervical cancer cells. We identified synergistic inhibition of cancer cell growth and migration upon combinational treatments. Here we report that the HDAC inhibitor Trichostatin A enhances the DNA targeting capacity and apoptosis inducing efficacy of AgNPs most probably due to its effect on chromatin condensation. These results point to the potential benefits of combinational application of HDAC inhibitors and AgNPs in novel cancer medication protocols. Copyright © 2016 Elsevier B.V. All rights reserved.

Combined Heat and Power Protocol for Uniform Methods Project | Advanced

Science.gov Websites

Manufacturing Research | NREL Combined Heat and Power Protocol for Uniform Methods Project Combined Heat and Power Protocol for Uniform Methods Project NREL developed a protocol that provides a ; is consistent with the scope and other protocols developed for the Uniform Methods Project (UMP

Implementation of a baby doll therapy protocol for people with dementia: Innovative practice.

PubMed

Braden, Barbara A; Gaspar, Phyllis M

2015-09-01

Dementia is exhibited by both emotional and physical states such as agitation. Chemical restraints, often used for agitated behaviors, are not always effective and produce untoward effects. Baby doll therapy is a nonpharmacologic therapy that can affect agitated behavior in dementia patients, yet a protocol for the therapy did not exist. An implementation protocol for doll therapy for those with dementia was developed and implemented with 16 residents in a dementia care center. Outcomes were measurements of the impact of the dolls on six areas of the resident's behavior and their reactions to the doll. Participants had an increase in level of happiness, activity/liveliness, interaction with staff and others, and ease of giving care. There was also a reduction in the level of anxiety. The increase in happiness was a statistically significant outcome. Baby doll therapy is an effective nonpharmacological approach for improving the well-being of patients with moderate to severe dementia. © The Author(s) 2014.

[Molecular remission induced by gemtuzumab ozogamicin in an elderly patient with relapsed acute promyelocytic leukemia].

PubMed

Yago, Kazuhiro; Aono, Maki; Shimada, Hideto

2010-04-01

A 79-year-old female with acute promyelocytic leukemia (APL) presented with second hematological relapse. She had been treated previously with modified AIDA protocol as the front-line therapy and had achieved complete remission. During ATRA maintenance therapy, the first hematological relapse occurred and she was treated with arsenic trioxide (ATO), achieving the second complete remission. After four courses of consolidation therapy of ATO, the second hematological relapse occurred. At this time, except for a transient effect of tamibarotene, neither arsenic trioxide nor combination chemotherapy was effective. The patient was then treated with two courses of gemtuzumab ozogamicin (GO) and achieved the third complete remission. At present, she is maintaining molecular remission more than one year after GO treatment. GO is considered to be a promising agent for elderly patients with relapsed acute promyelocytic leukemia resistant to arsenic trioxide.

Integrated cognitive-behavioral and psychodynamic psychotherapy for intimate partner violent men.

PubMed

Lawson, David M; Kellam, Melanie; Quinn, Jamie; Malnar, Stevie G

2012-06-01

Intimate partner violence (IPV) continue to have widespread negative effects on victims, children who witness IPV, and perpetrators. Current treatments have proven to be only marginally effective in stopping or reducing IPV by men. The two most prominent treatment approaches are feminist sociocultural and cognitive-behavioral therapy (CBT). The feminist sociocultural approach has been criticized for failing to adequately consider the therapeutic alliance, personality factors, and sole focus on patriarchy as the cause for IPV, whereas CBT has been criticized for failing to attend to motivation issues in treatment protocols. This article reviews the effectiveness of current treatments for partner-violent men, examines relationship and personality variables related to IPV and its treatment, and presents an emerging IPV treatment model that combines CBT and psychodynamic therapy. The article addresses how psychodynamic therapy is integrated into the more content-based elements of CBT. PsycINFO Database Record (c) 2012 APA, all rights reserved.

Diagnosis and treatment of neuropathic pain.

PubMed

Chong, M Sam; Bajwa, Zahid H

2003-05-01

Currently, no consensus on the optimal management of neuropathic pain exists and practices vary greatly worldwide. Possible explanations for this include difficulties in developing agreed diagnostic protocols and the coexistence of neuropathic, nociceptive and, occasionally, idiopathic pain in the same patient. Also, neuropathic pain has historically been classified according to its etiology (e.g., painful diabetic neuropathy, trigeminal neuralgia, spinal cord injury) without regard for the presumed mechanism(s) underlying the specific symptoms. A combined etiologic/mechanistic classification might improve neuropathic pain management. The treatment of neuropathic pain is largely empirical, often relying heavily on data from small, generally poorly-designed clinical trials or anecdotal evidence. Consequently, diverse treatments are used, including non-invasive drug therapies (antidepressants, antiepileptic drugs and membrane stabilizing drugs), invasive therapies (nerve blocks, ablative surgery), and alternative therapies (e.g., acupuncture). This article reviews the current and historical practices in the diagnosis and treatment of neuropathic pain, and focuses on the USA, Europe and Japan.

[The use of fenspiride for the combined treatment of exacerbation of chronic laryngitis].

PubMed

Ryabova, M A

The present study was carried out based at the Department of Otorhinolaryngology of I.P. Pavlov First State Medical University of Saint-Petersburg. The objective of this work was to elucidate the efficacy and safety of fenspiride therapy for the treatment of exacerbation of chronic laryngitis associated with an acute respiratory infection. The patients comprising the main group received fenspiride (Eurespal, 'Servier', France) at the standard dose in addition to the conventional therapy with the use of antibiotics, inhalation, and voice rest. The patients in the group of comparison were treated following the conventional protocol without fenspiride. The clinical symptoms evaluated based on the scoring system, the results of videolaryngoscopy, and computer-assisted analysis of the voice were compared before and after treatment in the patients of both groups. The results of the study have confirmed the high effectiveness and safety of fenspiride therapy of exacerbation of chronic laryngitis.

Physical therapy treatment in patients suffering from cervicogenic somatic tinnitus: study protocol for a randomized controlled trial

PubMed Central

2014-01-01

Background Tinnitus occurs in a large part of the general population with prevalences ranging from 10% to 15% in an adult population. One subtype is cervicogenic somatic tinnitus, arising from cervical spine dysfunctions, justifying cervical spine assessment and treatment. This study aims to investigate the effect of a standardized physical therapy treatment, directed to the cervical spine, on tinnitus. Additionally, a second aim is to identify a subgroup within the tinnitus population that benefits from physical therapy treatment. Methods and design This study is designed as a randomized controlled trial with delayed treatment design. Patients with severe subjective tinnitus (Tinnitus Functional Index (TFI) between 25 and 90 points), in combination with neck complaints (Neck Bournemouth Questionnaire (NBQ) >14 points) will be recruited from the University Hospital of Antwerp. Patients suffering from tinnitus with clear otological etiologies, severe depression, traumatic cervical spine injury, tumors, cervical spine surgery, or conditions in which physical therapy is contra-indicated, will be excluded. After screening for eligibility, baseline data such as TFI, NBQ, and a set of cervical biomechanical and sensorimotor tests will be collected. Patients are randomized in an immediate therapy group and in a group with a delayed start of therapy by 6 weeks. Patients will receive physical therapy with a maximum of 12 sessions of 30 min for a 6-week program. Data from the TFI and NBQ will be collected at baseline (week 0), at the start of therapy (weeks 0 or 6), at the end of therapy (weeks 6 or 12), 6 weeks after therapy (weeks 12 or 18), and 3 months after therapy (weeks 18 or 24). Secondary outcome measures will be collected at baseline and 6 weeks after the therapy (weeks 12 or 18), as the maximal therapy effect on the cervical spine dysfunctions is expected at that moment. Discussion This study is the first to investigate the effect of a standardized physical therapy treatment protocol on somatic tinnitus with a prospective comparative delayed design and with blinded evaluator for baseline, end of therapy, and 6 and 12 weeks after therapy. Trial registration 12 September 2013, ClinicalTrials.gov: NCT02016313 PMID:25056151

Risks and benefits of citrate anticoagulation for continuous renal replacement therapy.

PubMed

Shum, H P; Yan, W W; Chan, T M

2015-04-01

Heparin, despite its significant side-effects, is the most commonly used anticoagulant for continuous renal replacement therapy in critical care setting. In recent years, citrate has gained much popularity by improving continuous renal replacement therapy circuit survival and decreasing blood transfusion requirements. However, its complex metabolic consequences warrant modification in the design of the citrate-based continuous renal replacement therapy protocol. With thorough understanding of the therapeutic mechanism of citrate, a simple and practicable protocol can be devised. Citrate-based continuous renal replacement therapy can be safely and widely used in the clinical setting with appropriate clinical staff training.

Effectiveness of Aquatic Therapy vs Land-based Therapy for Balance and Pain in Women with Fibromyalgia: a study protocol for a randomised controlled trial.

PubMed

Rivas Neira, Sabela; Pasqual Marques, Amélia; Pegito Pérez, Irene; Fernández Cervantes, Ramón; Vivas Costa, Jamile

2017-01-19

Fibromyalgia is a disease with an increasing incidence. It impairs the quality of life of patients and decreases their functional capacity. Aquatic therapy has already been used for managing the symptoms of this syndrome. However, aquatic therapy has only recently been introduced as a treatment modality for improving proprioception in fibromyalgia. The main objective of this study is to determine the effectiveness of two physiotherapy protocols, one in and one out of water, for improving balance and decreasing pain in women with fibromyalgia. The study protocol will be a single-blind randomised controlled trial. Forty women diagnosed with fibromyalgia will be randomly assigned into 2 groups: Aquatic Therapy (n = 20) or Land-based Therapy (n = 20). Both interventions include 60-min therapy sessions, structured into 4 sections: Warm-up, Proprioceptive Exercises, Stretching and Relaxation. These sessions will be carried out 3 times a week for 3 months. Primary outcomes are balance (static and dynamic) and pain (intensity and threshold). Secondary outcomes include functional balance, quality of life, quality of sleep, fatigue, self-confidence in balance and physical ability. Outcome measures will be evaluated at baseline, at the end of the 3-month intervention period, and 6-weeks post-treatment. Statistical analysis will be carried out using the SPSS 21.0 program for Windows and a significance level of p ≤ 0.05 will be used for all tests. This study protocol details two physiotherapy interventions in women with fibromyalgia to improve balance and decrease pain: aquatic therapy and land-based therapy. In current literature there is a lack of methodological rigour and a limited number of studies that describe physiotherapy protocols to manage fibromyalgia symptoms. High-quality scientific works are required to highlight physiotherapy as one of the most recommended treatment options for this syndrome. Date of publication in ClinicalTrials.gov: 18/02/2016. ClinicalTrials.gov Identifier: NCT02695875 .

Emotional Freedom Techniques for Anxiety: A Systematic Review With Meta-analysis.

PubMed

Clond, Morgan

2016-05-01

Emotional Freedom Technique (EFT) combines elements of exposure and cognitive therapies with acupressure for the treatment of psychological distress. Randomized controlled trials retrieved by literature search were assessed for quality using the criteria developed by the American Psychological Association's Division 12 Task Force on Empirically Validated Treatments. As of December 2015, 14 studies (n = 658) met inclusion criteria. Results were analyzed using an inverse variance weighted meta-analysis. The pre-post effect size for the EFT treatment group was 1.23 (95% confidence interval, 0.82-1.64; p < 0.001), whereas the effect size for combined controls was 0.41 (95% confidence interval, 0.17-0.67; p = 0.001). Emotional freedom technique treatment demonstrated a significant decrease in anxiety scores, even when accounting for the effect size of control treatment. However, there were too few data available comparing EFT to standard-of-care treatments such as cognitive behavioral therapy, and further research is needed to establish the relative efficacy of EFT to established protocols.

Effectiveness of intensive smoking reduction counselling plus combination nicotine replacement therapy in promoting long-term abstinence in patients with chronic obstructive pulmonary disease not ready to quit smoking: Protocol of the REDUQ trial.

PubMed

Hagens, Petra; Pieterse, Marcel; van der Valk, Paul; van der Palen, Job

2017-12-01

Limited tobacco dependence treatment resources exist for smoking COPD patients not ready to quit. Smoking reduction may be a viable treatment approach if it prompts quit attempts and subsequent abstinence. This article describes the protocol of the REDUQ (REDUce and Quit) study, which examines whether smoking reduction counselling plus combination nicotine replacement therapy (NRT) is (cost-)effective in achieving long-term abstinence in smoking COPD patients not ready to quit. We conducted a two-centre, parallel-group, randomised controlled trial with 18 months follow-up in smoking outpatients with COPD. Patients not ready to quit within the next month but willing to reduce their smoking, were randomised to receive either intensive smoking reduction counselling plus combination NRT or a single information meeting plus self-help manual. Outcomes were assessed at baseline, 6, 12 and 18 months. The primary outcome is ≥ 1-year prolonged abstinence. Secondary outcomes are point prevalence abstinence, successful (i.e. ≥ 50%) smoking reduction, and incidence of quit attempts reported at follow-up assessments. Smoking status is biochemically verified by salivary cotinine and expired CO. Other variables include smoking-related cognitions, intention and motivation to reduce and quit smoking, withdrawal symptoms, health-related quality of life, symptoms of anxiety and depression, state of mindfulness, lung function, use of health care resources, and costs. The outcomes of the REDUQ trial will advance knowledge on treatment of smoking COPD patients not ready to quit. If (cost-)effective, the smoking reduction intervention can be offered to this difficult-to-treat target group as a valuable adjunct to smoking cessation treatment.

Continuous theta-burst stimulation combined with occupational therapy for upper limb hemiparesis after stroke: a preliminary study.

PubMed

Yamada, Naoki; Kakuda, Wataru; Kondo, Takahiro; Shimizu, Masato; Sageshima, Masashi; Mitani, Sugao; Abo, Masahiro

2014-12-01

The purpose of this study was to assess the safety, feasibility and efficacy of continuous theta-burst stimulation (cTBS) combined with intensive occupational therapy (OT) for upper limb hemiparesis after stroke. Ten patients with history of stroke and upper limb hemiparesis (age 62.0 ± 11.1 years, time since stroke 95.7 ± 70.2 months, mean ± SD) were studied. Each patient received 13 sessions, each comprising 160 s of cTBS applied to the skull on the area of the non-lesional hemisphere (using a 70-mm figure-8 coil, three pulse bursts at 50 Hz, repeated every 200 ms, i.e., 5 Hz, with total stimulation of 2,400 pulses), followed by intensive OT (comprising 120-min one-to-one training and 120-min self-training) during 15-day hospitalization. The motor function of the affected upper limb was evaluated by Fugl-Meyer Assessment (FMA) and Wolf Motor Function Test (WMFT) on the days of admission and discharge. All patients completed the 15-day protocol without any adverse effects. Treatment significantly increased the FMA score (from 46.6 ± 8.7 to 51.6 ± 8.2 points, p < 0.01) and shortened the log performance time of WMFT (from 2.5 ± 1.1 to 2.2 ± 1.2 s, p < 0.01). The 15-day protocol of cTBS combined with intensive OT is a safe and potentially useful therapeutic modality for upper limb hemiparesis after stroke.

S-1 versus S-1 plus cisplatin concurrent intensity modulated radiation therapy in the treatment of esophageal squamous cell carcinoma: Study protocol for a randomized controlled phase II trial.

PubMed

Wen, Yixue; Zhao, Zhenhuan; Miao, Jidong; Yang, Qilin; Gui, Yan; Sun, Mingqiang; Tian, Honggang; Jia, Qiang; Liao, Dongbiao; Yang, Chen; Du, Xiaobo

2017-12-01

Chemotherapy regimens are often a 2-drug regimen in concurrent chemotherapy and radiotherapy for esophageal cancer (EC). However, some retrospective studies have suggested that for patients with EC receiving radiotherapy combined with 2-drug chemotherapy have the severe toxicity. And S-1 alone with the combination of radiotherapy treatment effect is good, and achieved good clinical remission rate. The purpose of this trial is compare the efficacy and toxicity of combining S-1 or S-1 plus cisplatin with radiotherapy for esophageal squamous cell carcinoma. The study is a randomized, controlled, multicenter trial, comparing S-1 versus S-1 plus cisplatin concurrent radiotherapy for patients with esophageal squamous cell carcinoma. Eighty-eight patients with unresectable or medically unfit for surgery esophageal squamous cell carcinoma (clinical stage I to III), will randomly assigned to receive four cycles (2 concomitant and 2 postradiotherapy) S-1 or S-1 plus cisplatin along with radiotherapy 60-66 Gy/30 to 33 fractions. The primary outcome is complete response rate of primary tumor which will be measured by endoscopy and computer screen at 3 months after the completion of treatment. Secondary outcomes include survival and toxicity. To our knowledge, this study protocol is the first to test the effect between S-1 versus S-1 plus cisplatin concurrent intensity modulated radiation therapy in the treatment of esophageal squamous cell carcinoma. If the result will be the same effect and fewer side effects and less costly in S-1 plus radiotherapy. It will supply more treatment selection for esophageal squamous cell carcinoma.

Efficacy and Safety of Combined Oral and Enema Therapy Using Polyethylene Glycol 3350-Electrolyte for Disimpaction in Pediatric Constipation

PubMed Central

Yoo, Taeyeon

2017-01-01

Purpose We evaluated the efficacy and safety of combined oral and enema therapy using polyethylene glycol (PEG) 3350 with electrolyte solution for disimpaction in hospitalized children. Methods We retrospectively studied 28 children having functional constipation who received inpatient treatment between 2008 and 2016. The amount of oral PEG 3350 electrolyte solution administered was 50–70 mL/kg/d (PEG 3350, 3–4.1 g/kg/d), and an enema solution was administered 1–2 times a day as a single dose of 15–25 mL/kg (PEG 3350, 0.975–1.625 g/kg/d). A colon transit time (CTT) test based on the Metcalf protocol was performed in some patients. Results Administration of oral and enema doses of PEG 3350 electrolyte solution showed 2.1±0.3 times and 2.9±0.4 times, respectively. After disimpaction, the frequency of defecation increased from 2.2±0.3 per week to once a day (1.1±0.1 per day). The number of patients who complained of abdominal pain was reduced from 15 (53.6%) to 4 (14.3%). Before hospitalization, nine patients underwent a CTT test, and 5 of 9 patients (55.6%) were classified as belonging to a group showing abnormalities. And in some patients, mild adverse effects were noted. We examined electrolytes and osmolality before and after disimpaction in 16 of 28 patients, and no abnormalities were noted. Conclusion In terms of therapeutic efficacy and safety, combined oral and enema therapy using high-dose PEG 3350 with electrolytes is considered superior to conventional oral monotherapy or combined oral and enema therapy on an outpatient basis. PMID:29302506

Efficacy and Safety of Combined Oral and Enema Therapy Using Polyethylene Glycol 3350-Electrolyte for Disimpaction in Pediatric Constipation.

PubMed

Yoo, Taeyeon; Bae, Sun Hwan

2017-12-01

We evaluated the efficacy and safety of combined oral and enema therapy using polyethylene glycol (PEG) 3350 with electrolyte solution for disimpaction in hospitalized children. We retrospectively studied 28 children having functional constipation who received inpatient treatment between 2008 and 2016. The amount of oral PEG 3350 electrolyte solution administered was 50-70 mL/kg/d (PEG 3350, 3-4.1 g/kg/d), and an enema solution was administered 1-2 times a day as a single dose of 15-25 mL/kg (PEG 3350, 0.975-1.625 g/kg/d). A colon transit time (CTT) test based on the Metcalf protocol was performed in some patients. Administration of oral and enema doses of PEG 3350 electrolyte solution showed 2.1±0.3 times and 2.9±0.4 times, respectively. After disimpaction, the frequency of defecation increased from 2.2±0.3 per week to once a day (1.1±0.1 per day). The number of patients who complained of abdominal pain was reduced from 15 (53.6%) to 4 (14.3%). Before hospitalization, nine patients underwent a CTT test, and 5 of 9 patients (55.6%) were classified as belonging to a group showing abnormalities. And in some patients, mild adverse effects were noted. We examined electrolytes and osmolality before and after disimpaction in 16 of 28 patients, and no abnormalities were noted. In terms of therapeutic efficacy and safety, combined oral and enema therapy using high-dose PEG 3350 with electrolytes is considered superior to conventional oral monotherapy or combined oral and enema therapy on an outpatient basis.

[Cognitive therapy of trauma related guilt in patients with PTSD].

PubMed

Popiel, Agnieszka

2014-01-01

Various aspects of guilt are frequent problems of patients suffering from PTSD, though they have been included into the diagnostic criteria for PTSD just in the present version DSM-5. Some studies indicate limitation of effectiveness of exposure therapy in PTSD patients with predominant emotions of anger or guilt. The aim of this paper is to present cognitive conceptualization of guilt in PTSD proposed by Kubany, and a treatment protocol resulting from this conceptualization. The clinical application of the protocol is illustrated with preliminary results of systematic observation of 8 patients with moderate to severe PTSD who were treated with cognitive therapy for guilt followed by a standard prolonged exposure protocol. The cognitive therapy of guilt can be a valuable supplement for treatment of PTSD. This protocol can also be an inspiration for therapists working with patients with dysfunctional guilt as a problem in other than PTSD disorders--like depression or adjustment disorders. In discussion the place of guilt in treatment according to different (PE-Foa et al.; CPT-Resick et al.; CT-Ehlers and Clark) trauma focused therapy approaches is addressed, and the need for further studies is underlined.

The message of the survival curves: I. Composite analysis of long-term treatment studies in bipolar disorder.

PubMed

Frecska, Ede; Kovacs, Attila Istvan; Balla, Petra; Falussy, Linda; Ferencz, Akos; Varga, Zsofia

2012-09-01

There is a shortage of studies analyzing the time course of recurrent episodes and comparing effectiveness of long-term treatments in bipolar disorder. 'Number needed to treat' (NNT) analyses have been proven to be useful for clinically meaningful comparisons, but results vary considerably among studies. The survival curves of different trials also show a great variability preventing reliable conclusions on the time course of maintenance therapies. The variance of survival analyses on long-term medication management can be reduced with increasing the statistical power by combining the life-tables of individual studies. In this study the survival tables of 28 studies on maintenance treatment of bipolar disorder were reconstructed from the published diagrams, and the numbers of relapsed patients in the original studies were estimated for plotting composite survival curves of an inactive, mono- and combination therapy arm. The review was finally based on 5231 subjects. The resulting composite diagrams indicate that within the first year 48% of patients on monotherapy, and 35% on combination therapy experienced recurrence of any affective episode ('early relapsers'). The rest of the patient population was affected by recurrences in a smaller rate over a more extended period of time ('late relapsers'). For a favorable outcome at 40 months of episode prevention in bipolar disorder the NNT was 6 for mono- and 3 for combination therapy. Log-rank analyses of the composite data supported the effectiveness of both medication protocols over placebo, and the superiority of drug combination over monotherapy; though there were some indications of decreased efficacy in the two treatment arms after extended maintenance. Composite analysis offers increased statistical power for studying the time course of survival data. Mood episodes in bipolar disorder are likely to recur early on and relapses in "real-life" can be more frequent than the rates published here. Our results favor combination therapy for the long-term management of bipolar disorder. Concerns are expressed that NNT analyses have significant limitations when applied to recurring events with cumulative deterioration instead of cases where cumulative improvement is expected over time.

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 Vascular Disrupting Agent 5,6-Dimethylxanthenone-4-Acetic Acid Improves the Antitumor Efficacy and Shortens Treatment Time Associated with Photochlor-sensitized Photodynamic Therapy In Vivo

PubMed Central

Seshadri, Mukund; Bellnier, David A.

2010-01-01

In this report, we examined the antitumor activity of photodynamic therapy (PDT) in combination with 5,6-dimethylxanthenone- 4-acetic acid (DMXAA), a vascular disrupting agent currently undergoing clinical evaluation. BALB/c mice bearing subcutaneous CT-26 colon carcinomas were treated with PDT using the second-generation chlorin-based sensitizer, 2-[1-hexyloxyethyl]-2-devinyl pyropheophorbide-a (Photochlor) with or without DMXAA. Long-term (60-days) treatment outcome, induction of tumor necrosis factor-alpha (TNF-α) and interleukin- 6 (IL-6), vascular damage (microvessel density, MVD) were evaluated as endpoints. In addition, treatment selectivity was evaluated using magnetic resonance imaging (MRI) and the foot response assay. A highly synergistic interaction was observed with the combination of low-dose DMXAA and PDT (48 J cm−2 at 112 mW cm−2) resulting in ~60% long-term cures. The duration of the PDT session for this combination therapy protocol was only 7 min, while the duration of a monotherapy PDT session, selected to yield the equivalent cure rate, was 152 min. MRI showed markedly less peritumoral edema after DMXAA + short-duration PDT compared with long-duration PDT monotherapy. Similarly, DMXAA + PDT caused significantly less phototoxicity to normal mouse foot tissue than PDT alone. Increased induction of cytokines TNF-α and IL-6 (P < 0.001) was observed at 4 h followed by extensive vascular damage, demonstrated by a significant reduction in MVD at 24 h after combination treatment. In conclusion, Photochlorsensitized PDT in combination with DMXAA exhibits superior efficacy and improved selectivity with clinically feasible illumination schemes. Clinical evaluation of this novel combination strategy is currently being planned. PMID:18643909

Encouraging physician appropriate prescribing of non-steroidal anti-inflammatory therapies: protocol of a randomized controlled trial [ISRCTN43532635

PubMed Central

Doupe, Malcolm; Katz, Alan; Kvern, Brent; Manness, Lori-Jean; Metge, Colleen; Thomson, Glen TD; Morrison, Laura; Rother, Kat

2004-01-01

Background Traditional non-steroidal anti-inflammatory drugs (NSAIDs) are a widely used class of therapy in the treatment of chronic pain and inflammation. The drugs are effective and can be relatively inexpensive thanks to available generic versions. Unfortunately the traditional NSAIDs are associated with gastrointestinal complications in a small proportion of patients, requiring costly co-therapy with gastro-protective agents. Recently, a new class of non-steroidal anti-inflammatory agents known as coxibs has become available, fashioned to be safer than the traditional NSAIDs but priced considerably higher than the traditional generics. To help physicians choose appropriately and cost-effectively from the expanded number of anti-inflammatory therapies, scientific bodies have issued clinical practice guidelines and third party payers have published restricted reimbursement policies. The objective of this study is to determine whether an educational intervention can prompt physicians to adjust their prescribing in accordance with these expert recommendations. Methods This is an ongoing, randomized controlled trial. All primary care physicians in Manitoba, Canada have been randomly assigned to a control group or an intervention study group. The educational intervention being evaluated consists of an audit and feedback mechanism combined with optional participation in a Continuing Medical Education interactive workshop. The primary outcome of the study is the change, from pre-to post-intervention, in physicians' appropriate prescribing of non-steroidal anti-inflammatory therapies for patients requiring chronic treatment. Three classes of non-steroidal anti-inflammatory therapies have been identified: coxib therapy, traditional NSAID monotherapy, and traditional NSAID therapy combined with gastro-protective agents. Appropriate prescribing is defined based on international clinical practice guidelines and the provincial drug reimbursement policy in Manitoba. PMID:15327694

Adoptive cell transfer therapy for malignant gliomas.

PubMed

Ishikawa, Eiichi; Takano, Shingo; Ohno, Tadao; Tsuboi, Koji

2012-01-01

To date, various adoptive immunotherapies have been attempted for treatment of malignant gliomas using nonspecific and/or specific effector cells. Since the late 1980s, with the development of rIL-2, the efficacy of lymphokine-activated killer (LAK) cell therapy with or without rIL-2 for malignant gliomas had been tested with some modifications in therapeutic protocols. With advancements in technology, ex vivo expanded tumor specific cytotoxic T-lymphocytes (CTL) or those lineages were used in clinical trials with higher tumor response rates. In addition, combinations of those adoptive cell transfer using LAK cells, CTLs or natural killer (NK) cells with autologous tumor vaccine (ATV) therapy were attempted. Also, a strategy of high-dose (or lymphodepleting) chemotherapy followed by adoptive cell transfer has been drawing attentions recently. The most important role of these clinical studies using cell therapy was to prove that these ex vivo expanded effector cells could kill tumor cells in vivo. Although recent clinical results could demonstrate radiologic tumor shrinkage in a number of cases, cell transfer therapy alone has been utilized less frequently, because of the high cost of ex vivo cell expansion, the short duration of antitumor activity in vivo, and the recent shift of interest to vaccine immunotherapy. Nevertheless, NK cell therapy using specific feeder cells or allergenic NK cell lines have potentials to be a good choice of treatment because of easy ex vivo expansion and their efficacy especially when combined with vaccine therapy as they are complementary to each other. Also, further studies are expected to clarify the efficacy of the high-dose chemotherapy followed by a large scale cell transfer therapy as a new therapeutic strategy for malignant gliomas.

Analysis of different therapeutic protocols for osteonecrosis of the jaw associated with oral and intravenous bisphpsphonates

PubMed Central

Bermúdez-Bejarano, Elena-Beatriz; Serrera-Figallo, María-Ángeles; Gutiérrez-Corrales, Aida; Romero-Ruiz, Manuel-María; Castillo-de-Oyagüe, Raquel; Gutiérrez-Pérez, José-Luis; Machuca-Portillo, Guillermo

2017-01-01

Introduction Chemotherapy-associated osteonecrosis of the jaw caused by bisphosphonates is an exposure of necrotic bone with more than eight weeks of evolution that is attributable to bisphosphonates and no prior radiation therapy. Its etiopathogenesis remains unknown, although there are two hypotheses that may explain it: the drug’s mechanism of action, and the risk factors that can lead to osteonecrosis. There is a wide range of treatment options for managing chemotherapy-associated osteonecrosis of the jaw, from conservative treatments to surgical procedures of varying levels of invasiveness, which are sometimes supplemented with adjuvant therapies. Objectives The objective of this article is to group the therapeutic options for osteonecrosis of the jaw (ONJ) into seven different protocols and to evaluate their effectiveness in relation to stage of ONJ. Material and Methods A literature review was carried out in PubMed following the PRISMA criteria. A total of 47 were collected after compiling a series of variables that define ONJ, applied treatments, and the clinical results obtained. Results and Discussion The 47 articles selected have a low to average estimated risk of bias and are of moderate to good quality. According to the data obtained, Protocol 3 (conservative treatment, clinical and radiological follow-up, minimally invasive surgical treatment, and adjuvant therapies) is the most favorable approach for ONJ lesions caused by oral bisphosphonates. For lesions caused by intravenous bisphosphonates, Protocol 2 (conservative treatment, clinical and radiological follow-up, minimally invasive surgical treatment, and no adjuvant therapies) is the best approach. When comparing the different stages of ONJ, Protocol 1 (conservative treatment, clinical and radiological follow-up) promotes better healing of Stage 1 ONJ lesions caused by orally administered bisphosphonates, and Protocol 3 is recommended for Stage II. For ONJ lesions attributable to intravenous bisphosphonates, Protocol 7 (conservative treatment, clinical and radiological follow-up, and adjuvant therapies) provides the best results in Stage 0; in Stages I, II, and III, Protocol 1 gives better results. Key words:Bisphosphonates, bronj, therapeutic protocol, clinical result. PMID:27918742

Photodynamic therapy as a novel treatment for halitosis in adolescents: study protocol for a randomized controlled trial.

PubMed

Lopes, Rubia Garcia; de Godoy, Camila Haddad Leal; Deana, Alessandro Melo; de Santi, Maria Eugenia Simões Onofre; Prates, Renato Araujo; França, Cristiane Miranda; Fernandes, Kristianne Porta Santos; Mesquita-Ferrari, Raquel Agnelli; Bussadori, Sandra Kalil

2014-11-14

Halitosis is a common problem that affects a large portion of the population worldwide. The origin of this condition is oral in 90% and systemic in 10% of cases. The unpleasant odor is mainly the result of volatile sulfur compounds produced by Gram-negative bacteria. However, it has recently been found that anaerobic Gram-positive bacteria also produce hydrogen sulfide (H2S) in the presence of amino acids, such as cysteine. Light, both with and without the use of chemical agents, has been used to induce therapeutic and antimicrobial effects. In photodynamic therapy, the antimicrobial effect is confined to areas covered by photosensitizing dye. The aim of the present study is to evaluate the antimicrobial effect of photodynamic therapy on halitosis in adolescents through the analysis of volatile sulfur compounds measured using gas chromatography and microbiological analysis of coated tongue. A quantitative clinical trial will be carried out involving 60 adolescents randomly divided into the following groups: group 1 will receive treatment with a tongue scraper, group 2 will receive photodynamic therapy applied to the posterior two-thirds of the dorsum of the tongue, and group 3 will receive combined treatment (tongue scraper and photodynamic therapy). Gas chromatography (OralChromaTM) and microbiological analysis will be used for the diagnosis of halitosis at the beginning of the study. Post-treatment evaluations will be conducted at one hour and 24 hours after treatment. The statistical analysis will include the Shapiro-Wilk test for the determination of the distribution of the data. If normal distribution is demonstrated, analysis of variance followed by Tukey's test will be used to compare groups. The Kruskal-Wallis test followed by the Student-Newman-Keuls test will be used for data with non-normal distribution. Either the paired t-test or the Wilcoxon test will be used to compare data before and after treatment, depending on the distribution of the data. The results of this trial will determine the efficacy of using photodynamic therapy alone or in combination with a tongue scraper to treat bad breath in adolescents. The protocol for this study was registered with Clinical Trials (registration number NCT02007993) on 10 December 2013.

Combinatorial drug delivery strategy employing nano-curcumin and nano-MiADMSA for the treatment of arsenic intoxication in mouse.

PubMed

Kushwaha, Pramod; Yadav, Abhishek; Samim, M; Flora, S J S

2018-04-25

Chelation therapy is the mainstream treatment for heavy metal poisoning. Apart from this, therapy using antioxidant/herbal extracts are the other strategies now commonly being tried for the treatment. We have previously reported individual beneficial efficacy of nanoparticle mediated administration of an antioxidant like 'curcumin' and an arsenic chelator 'monoisoamyl 2,3-dimercaptosuccinic acid (MiADMSA)' for the treatment of arsenic toxicity compared to bulk drugs. The present paper investigates our hypothesis that a combination drug delivery therapy employing two nanosystems, a chelator and a strong antioxidant, may produce more pronounced therapeutic effects compared to individual effects in the treatment of arsenic toxicity. An in-vivo study was conducted wherein arsenic as sodium arsenite (100 ppm) was administered in drinking water for 5 months to Swiss albino mice. This was followed by a treatment protocol comprising of curcumin encapsulated chitosan nanoparticles (nano-curcumin, 15 mg/kg, orally for 1 month) either alone or in combination with MiADMSA encapsulated polymeric nanoparticles (nano-MiADMSA, 50 mg/kg for last 5 days) to evaluate the therapeutic potential of the combination treatment. Our results demonstrated that co-treatment with nano-curcumin and nano-MiADMSA provided beneficial effects in a synergistic way on the adverse changes in oxidative stress parameters and metal status induced by arsenic. Copyright © 2018 Elsevier B.V. All rights reserved.

Paracoccidioidomycosis vaccine

PubMed Central

Travassos, Luiz R.; Taborda, Carlos P.

2012-01-01

Paracoccidioidomycosis is a granulomatous pulmonary infection that is generally controlled by chemotherapy. The efficacy of treatment, however, is limited by the status of the host immune response. The inhibition of a Th-2 immunity or the stimulation of Th-1 cytokines generally increases the efficacy of antifungal drugs.1 This has been achieved by immunization with an internal peptide of the major diagnostic antigen gp43 of Paracoccidioides brasiliensis. Peptide 10 (QTLIAIHTLAIRYAN) elicits an IFN-γ rich Th-1 immune response that protects against experimental intratracheal infection by this fungus. The combination of chemotherapy with P10 immunization showed additive protective effect even after 30 d of infection or in anergic mice, rendering in general, increased production of IL-12 and IFN-γ and reduction of IL-4 and IL-10. Immunotherapy with P10 even in the absence of simultaneous chemotherapy has been effective using various protocols, adjuvants, nanoparticles, P10-primed dendritic cells, and especially a combination of plasmids encoding the P10 minigene and IL-12. Gene therapy, in a long-term infection protocol succeeded in the virtual elimination of the fungus, preserving the lung structure, free from immunopathological side effects. PMID:22894948

Postinjury Exercise and Platelet-Rich Plasma Therapies Improve Skeletal Muscle Healing in Rats But Are Not Synergistic When Combined.

PubMed

Contreras-Muñoz, Paola; Torrella, Joan Ramon; Serres, Xavier; Rizo-Roca, David; De la Varga, Meritxell; Viscor, Ginés; Martínez-Ibáñez, Vicente; Peiró, José Luis; Järvinen, Tero A H; Rodas, Gil; Marotta, Mario

2017-07-01

Skeletal muscle injuries are the most common sports-related injury and a major concern in sports medicine. The effect of platelet-rich plasma (PRP) injections on muscle healing is still poorly understood, and current data are inconclusive. To evaluate the effects of an ultrasound-guided intramuscular PRP injection, administered 24 hours after injury, and/or posttraumatic daily exercise training for 2 weeks on skeletal muscle healing in a recently established rat model of skeletal muscle injury that highly mimics the muscle trauma seen in human athletes. Controlled laboratory study. A total of 40 rats were assigned to 5 groups. Injured rats (medial gastrocnemius injury) received a single PRP injection (PRP group), daily exercise training (Exer group), or a combination of a single PRP injection and daily exercise training (PRP-Exer group). Untreated and intramuscular saline-injected animals were used as controls. Muscle force was determined 2 weeks after muscle injury, and muscles were harvested and evaluated by means of histological assessment and immunofluorescence microscopy. Both PRP (exhibiting 4.8-fold higher platelet concentration than whole blood) and exercise training improved muscle strength (maximum tetanus force, TetF) in approximately 18%, 20%, and 30% of rats in the PRP, PRP-Exer, and Exer groups, respectively. Specific markers of muscle regeneration (developmental myosin heavy chain, dMHC) and scar formation (collagen I) demonstrated the beneficial effect of the tested therapies in accelerating the muscle healing process in rats. PRP and exercise treatments stimulated the growth of newly formed regenerating muscle fibers (1.5-, 2-, and 2.5-fold increase in myofiber cross-sectional area in PRP, PRP-Exer, and Exer groups, respectively) and reduced scar formation in injured skeletal muscle (20%, 34%, and 41% of reduction in PRP, PRP-Exer, and Exer groups, respectively). Exercise-treated muscles (PRP-Exer and Exer groups) had significantly reduced percentage of dMHC-positive regenerating fibers (35% and 47% decrease in dMHC expression, respectively), indicating that exercise therapies accelerated the muscle healing process witnessed by the more rapid replacement of the embryonic-developmental myosin isoform by mature muscle myosin isoforms. Intramuscular PRP injection and, especially, treadmill exercise improve histological outcome and force recovery of the injured skeletal muscle in a rat injury model that imitates sports-related muscle injuries in athletes. However, there was not a synergistic effect when both treatments were combined, suggesting that PRP does not add any beneficial effect to exercise-based therapy in the treatment of injured skeletal muscle. This study demonstrates the efficacy of an early active rehabilitation protocol or single intramuscular PRP injection on muscle recovery. The data also reveal that the outcome of the early active rehabilitation is adversely affected by the PRP injection when the two therapies are combined, and this could explain why PRP therapies have failed in randomized clinical trials where the athletes have adhered to postinjection rehabilitation protocols based on the principle of early, active mobilization.

Boron neutron capture therapy (BNCT) for the treatment of liver metastases: biodistribution studies of boron compounds in an experimental model.

PubMed

Garabalino, Marcela A; Monti Hughes, Andrea; Molinari, Ana J; Heber, Elisa M; Pozzi, Emiliano C C; Cardoso, Jorge E; Colombo, Lucas L; Nievas, Susana; Nigg, David W; Aromando, Romina F; Itoiz, Maria E; Trivillin, Verónica A; Schwint, Amanda E

2011-03-01

We previously demonstrated the therapeutic efficacy of different boron neutron capture therapy (BNCT) protocols in an experimental model of oral cancer. BNCT is based on the selective accumulation of (10)B carriers in a tumor followed by neutron irradiation. Within the context of exploring the potential therapeutic efficacy of BNCT for the treatment of liver metastases, the aim of the present study was to perform boron biodistribution studies in an experimental model of liver metastases in rats. Different boron compounds and administration conditions were assayed to determine which administration protocols would potentially be therapeutically useful in in vivo BNCT studies at the RA-3 nuclear reactor. A total of 70 BDIX rats were inoculated in the liver with syngeneic colon cancer cells DHD/K12/TRb to induce the development of subcapsular tumor nodules. Fourteen days post-inoculation, the animals were used for biodistribution studies. We evaluated a total of 11 administration protocols for the boron compounds boronophenylalanine (BPA) and GB-10 (Na(2)(10)B(10)H(10)), alone or combined at different dose levels and employing different administration routes. Tumor, normal tissue, and blood samples were processed for boron measurement by atomic emission spectroscopy. Six protocols proved potentially useful for BNCT studies in terms of absolute boron concentration in tumor and preferential uptake of boron by tumor tissue. Boron concentration values in tumor and normal tissues in the liver metastases model show it would be feasible to reach therapeutic BNCT doses in tumor without exceeding radiotolerance in normal tissue at the thermal neutron facility at RA-3. © Springer-Verlag 2010

Boron Neutron Capture Therapy (BCNT) for the Treatment of Liver Metastases: Biodistribution Studies of Boron Compounds in an Experimental Model

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

Marcela A. Garabalino; Andrea Monti Hughes; Ana J. Molinari

2011-03-01

Abstract We previously demonstrated the therapeutic efficacy of different boron neutron capture therapy (BNCT) protocols in an experimental model of oral cancer. BNCT is based on the selective accumulation of 10B carriers in a tumor followed by neutron irradiation. Within the context of exploring the potential therapeutic efficacy of BNCT for the treatment of liver metastases, the aim of the present study was to perform boron biodistribution studies in an experimental model of liver metastases in rats. Different boron compounds and administration conditions were assayed to determine which administration protocols would potentially be therapeutically useful in in vivo BNCT studiesmore » at the RA-3 nuclear reactor. A total of 70 BDIX rats were inoculated in the liver with syngeneic colon cancer cells DHD/K12/TRb to induce the development of subcapsular tumor nodules. Fourteen days post-inoculation, the animals were used for biodistribution studies. We evaluated a total of 11 administration protocols for the boron compounds boronophenylalanine (BPA) and GB-10 (Na210B10H10), alone or combined at different dose levels and employing different administration routes. Tumor, normal tissue, and blood samples were processed for boron measurement by atomic emission spectroscopy. Six protocols proved potentially useful for BNCT studies in terms of absolute boron concentration in tumor and preferential uptake of boron by tumor tissue. Boron concentration values in tumor and normal tissues in the liver metastases model show it would be feasible to reach therapeutic BNCT doses in tumor without exceeding radiotolerance in normal tissue at the thermal neutron facility at RA-3.« less

Desensitization Protocol in Recipients of Deceased Kidney Donor With Donor-Specific Antibody-Low Titers.

PubMed

Kanter Berga, J; Sancho Calabuig, A; Gavela Martinez, E; Puig Alcaraz, N; Avila Bernabeu, A; Crespo Albiach, J; Molina Vila, P; Beltrán Catalan, S; Pallardó Mateu, L

2016-11-01

Kidney transplantation is the better option for end-stage renal disease (ESRD), but for patients with human leukocyte antigen (HLA) sensitization, the wait times are significantly longer than for patients without antibodies. Many desensitization protocols have been described involving strong immunosuppression, the use of apheresis, and B-cell-modulating therapies. We have designed a desensitization protocol from day 0 for deceased donor kidney transplantation. Our aim was to present our initial experience with five kidney transplant patients. All patients had a negative complement-dependent cytotoxicity cross-match. The desensitization protocol included five to seven doses of thymoglobulin (1.25 mg/kg) and three sessions of plasmapheresis (PP) within the first week after transplantation, with intravenous immunoglobulin (500 mg/kg) after each PP session and one dose of rituximab on day 8. The presence of donor-specific antibodies (DSA) was analyzed by use of Luminex technology; levels between 1000 and 3000 mean fluorescence intensity were considered for desensitization. The median age was 44 years and median renal replacement therapy time was 9 years. All recipients presented 1 to 3 DSA specificities. There were no severe side effects related to PP, infusion of intravenous immunoglobulin, or rituximab. The median follow-up period was 19.3 months. Median serum creatinine level at last follow-up was 1.7 mg/dL. A kidney biopsy was performed in all patients. Graft and patient survival was 100%. Until now, few data are available concerning whether HLA-incompatible kidney transplantation after desensitization would benefit patients with ERSD. The desensitization strategy using the combination of PP, low doses of intravenous immunoglobulin, and rituximab at our center resulted in a satisfactory clinical outcome. Copyright © 2016 Elsevier Inc. All rights reserved.

Purification of Bacteriophages Using Anion-Exchange Chromatography.

PubMed

Vandenheuvel, Dieter; Rombouts, Sofie; Adriaenssens, Evelien M

2018-01-01

In bacteriophage research and therapy, most applications ask for highly purified phage suspensions. The standard technique for this is ultracentrifugation using cesium chloride gradients. This technique is cumbersome, elaborate and expensive. Moreover, it is unsuitable for the purification of large quantities of phage suspensions.The protocol described here, uses anion-exchange chromatography to bind phages to a stationary phase. This is done using an FLPC system, combined with Convective Interaction Media (CIM ® ) monoliths. Afterward, the column is washed to remove impurities from the CIM ® disk. By using a buffer solution with a high ionic strength, the phages are subsequently eluted from the column and collected. In this way phages can be efficiently purified and concentrated.This protocol can be used to determine the optimal buffers, stationary phase chemistry and elution conditions, as well as the maximal capacity and recovery of the columns.

Testing the Integrity of a Psychotherapy Protocol: Assessment of Adherence and Competence.

ERIC Educational Resources Information Center

Waltz, Jennifer; And Others

1993-01-01

Treatment manuals and protocols have made delivery of particular therapies purer and more consistent, initiating a demand that researchers not only use treatment manuals to improve purity of their therapy but document that their efforts to achieve purity have been successful. Strategies that have been used to document treatment integrity are…

Current Trend of Antimicrobial Prescription for Oral Implant Surgery Among Dentists in India.

PubMed

Datta, Rahul; Grewal, Yasmin; Batth, J S; Singh, Amandeep

2014-12-01

The aim of our study was to evaluate antimicrobial prescription behaviour amongst dentists performing oral implant surgery in India. Dentists performing oral implant surgery from different parts of India were personally approached during various national events such as conferences and academic meetings and information regarding their prescription habits for antimicrobial agents in routine oral implant surgery was collected using a structured questionnaire. Out of a total sample of 332 dentists, 85.5 % prescribed 17 different groups or combinations of antibiotics routinely for oral implant surgery in the normal healthy patient. Majority preferred the peri-operative protocol of drug therapy (72.2 %) with variable and prolonged duration of therapy after surgery, ranging from 3 to 10 days. An antimicrobial mouthwash was routinely prescribed by all the doctors (14.5 %) not in favour of prescribing antimicrobials in a normal healthy patient. Our findings suggest that there is a trend of antimicrobial agent misuse by dentists performing oral implant surgery in India, both in terms of drugs used and the protocols prescribed. The majority of these dentists prescribed a variety of antimicrobial agents for prolonged durations routinely even in the normal, healthy patients.

Favourably effective formulation of sodium iodide and salicylic acid plus professional hygiene in patients affected by desquamative gingivitis.

PubMed

Carcieri, P; Broccoletti, R; Giacometti, S; Gambino, A; Conrotto, D; Cabras, M; Arduino, P G

2016-01-01

The aim of this prospective pilot study was to evaluate the efficiency of an oral hygiene protocol, in combination with a solution of sodium iodide associated to salicylic acid (SISA), in patients affected by desquamative gingivitis (DG). Twenty patients not totally responding to conventional topical therapies, were selected. They received oral hygiene instructions with non-surgical periodontal therapy in a 21-day cohort study (during 3 weekly appointments). The SISA was used at the end of each session, with an impregnated gauze (with 5 ml of the solution) applied for 15 minutes for the upper jaw, and for a further 15 minutes with a new gauze for the lower. Evaluated clinical outcome variables included the full mouth plaque (FMPS) and bleeding (FMBS) scores, probing depth, patient related outcome and clinical gingival signs. Two months after concluding the planned protocol, a statistically significant reduction was observed for FMPS (P=0.032), FMBS (P=0.038), reported pain (P=0.000) and gingival clinical improvement (P=0.005). Topical application of SISA and professional oral hygiene procedures are connected with improvement of gum status, and decrease of related pain in subjects affected by severe DG.

A single-group pretest posttest design using full kinetic chain manipulative therapy with rehabilitation in the treatment of 18 patients with hip osteoarthritis.

PubMed

Brantingham, James W; Globe, Gary A; Cassa, Tammy Kay; Globe, Denise; de Luca, Katie; Pollard, Henry; Lee, Felix; Bates, Charles; Jensen, Muffit; Mayer, Stephan; Korporaal, Charmaine

2010-01-01

Hip osteoarthritis (HOA) affects 30 million Americans or more, and is a leading cause of disability, suffering, and pain. Standard treatments are minimally effective and carry significant risk and expense. This study assessed treatment effects of a chiropractic protocol for HOA. Eighteen individuals, who did not qualify due to low baseline Western Ontario and McMaster Osteoarthritis Index scores (WOMAC) for other ongoing HOA randomized control trials, were selected. A prospectively planned protocol, consisting of axial manipulation to the affected hip with modified Thomas and active assisted stretch, was combined with full kinetic chain treatment or manipulative therapy to the spine, knee, ankle, or foot and assessed with use of valid and reliable outcome measures. The primary outcome measure, the Overall Therapy Effectiveness Tool, was assessed with chi(2) and demonstrated that 83.33% of participants were improved after the ninth visit, P = .005, and 78% improved at the 3-month follow-up, P = .018. Using the paired t test, WOMAC was improved 64% at the ninth visit, P = .000, and 47% at follow-up, P = .016. In HOA patients with lower WOMAC scores, a highly organized HOA treatment appears to have resulted in statistically and clinically meaningful intragroup changes in the Overall Effectiveness Therapy Tool, WOMAC, Harris Hip Scale, and range of motion, all with P

Development of a quantitative tool to assess the content of physical therapy for infants.

PubMed

Blauw-Hospers, Cornill H; Dirks, Tineke; Hulshof, Lily J; Hadders-Algra, Mijna

2010-01-01

The study aim was to describe and quantify physical therapy interventions for infants at high risk for developmental disorders. An observation protocol was developed based on knowledge about infant physical therapy and analysis of directly observable physiotherapeutic (PT) actions. The protocol's psychometric quality was assessed. Videos of 42 infant physical therapy sessions at 4 or 6 months of corrected age were analyzed. The observation protocol classified PT actions into 8 mutually exclusive categories. Virtually all PT actions during treatment could be classified. Inter- and intrarater agreements were satisfactory (intraclass correlations, 0.68-1.00). Approximately 40% of treatment time was spent challenging the infant to produce motor behavior by themselves, whereas approximately 30% of time facilitation techniques were applied. Tradition-based sessions could be differentiated from function-oriented ones. It is possible to document PT actions during physical therapy treatment of infants at high risk for cerebral palsy in a systematic, standardized, and reliable way.

Frequency of "Pocket" Hematoma in Patients Receiving Vitamin K Antagonist and Antiplatelet Therapy at the Time of Pacemaker or Cardioverter Defibrillator Implantation (from the POCKET Study).

PubMed

Malagù, Michele; Trevisan, Filippo; Scalone, Antonella; Marcantoni, Lina; Sammarco, Giuseppe; Bertini, Matteo

2017-04-01

In patients undergoing cardiac device implantation, anticoagulant and antiplatelet therapy are associated with an increased risk of pocket hematoma. In case of vitamin K antagonist therapy, a strategy of continued warfarin with no heparin bridge showed a reduction of pocket hematoma. Evidence regarding antiplatelet therapy management is limited. This is a single-center observational study which reflects our systematic approach to the problem. In 2012, we proposed an improved management protocol for anticoagulant and antiplatelet therapy (no-bridge protocol) based on individual thromboembolic risk stratification, noninterruption of oral anticoagulation, no bridge with heparin and elastic adherence compression bandage. The primary end point was the incidence of clinically significant pocket hematoma in the first 30 days after implantation. A total of 1,035 patients were enrolled, of whom 522 received the standard management and 513 the new protocol. The primary end point occurred in 34 patients of the standard management group and 8 patients of the no-bridge protocol group (6.5% vs 1.6%, p <0.001). Patients in the standard management group had a higher incidence of pocket infections (2.3% vs 0.6%, p = 0.02), lead dislodgements (4.8% vs 2.1%, p = 0.02), and thromboembolic events (1.3% vs 0.0%, p <0.01). On a multivariate analysis, heparin and coronary artery disease were independent predictors of pocket hematoma (relative risk [RR] 3.48, 95% confidence interval [CI] 1.55 to 7.83 and RR 2.43, 95% CI 1.25 to 4.76, respectively), whereas the no-bridge protocol was associated with a reduction of pocket hematoma (RR 0.33, 95% CI 0.14 to 0.76). New anticoagulant and antiplatelet therapy management protocol was associated with a reduced incidence of clinically significant pocket hematomas, thromboembolic events, pocket infections, and lead dislodgements. Copyright © 2017 Elsevier Inc. All rights reserved.

Acute Pain Service and multimodal therapy for postsurgical pain control: evaluation of protocol efficacy.

PubMed

Moizo, E; Berti, M; Marchetti, C; Deni, F; Albertin, A; Muzzolon, F; Antonino, A

2004-11-01

The institution of a postoperative Acute Pain Control Service is mandatory to improve the control of pain induced by surgical injury. Treatment of postoperative pain may be achieved using a combination of analgesic agents and techniques, reducing the incidence of side effects owing to the lower doses of the individual drugs. In 1997 we established an Acute Pain Service (APS) at the San Raffaele Hospital in Milan. The aim of this study was to assess the efficacy and safety of our APS both in terms of treatment protocols and organisational issues. In this prospective observational study we included 592 patients undergoing abdominal, gynecological, or orthopedic surgery with severe expected pain. According to general guidelines on pain treatment, the patients were assigned to different treatment protocols based on the kind of operation. All protocols were based on the multimodal therapy, with the association of nonsteroidal anti-inflammatory drugs (NSAIDS), opioids and regional anesthesia techniques. During the first 48 h of the postoperative period we recorded vital signs, level of pain and occurrence of any side effect. Our analgesic protocols proved to be effective and safe (low incidence of side effects) for every surgery. The incidence of postoperative nausea and vomiting was higher in patients receiving patient-controlled morphine than that with continuous epidural or nerve block. After lower abdominal surgery, pain at movement at 24 h was significantly lower in the epidural group than in the Patient Control Analgesia group. Nausea and vomiting, numbness and paresthesias at the lower limbs were higher in gynecological patients. A larger percentage of orthopedic patients in the epidural group reported numbness and paresthesias at the lower limbs in comparison with patients receiving continuous peripheral nerve block. In agreement with previous literature, this study confirmed that a multimodal approach to pain treatment provides an adequate control of postoperative pain, minimizing side effects.

Comparing systemic therapy and cognitive behavioral therapy for social anxiety disorders: study protocol for a randomized controlled pilot trial.

PubMed

Hunger, Christina; Hilzinger, Rebecca; Koch, Theresa; Mander, Johannes; Sander, Anja; Bents, Hinrich; Schweitzer, Jochen

2016-03-31

Social anxiety disorders are among the most prevalent anxiety disorders in the general population. The efficacy of cognitive behavioral therapy (CBT) for social anxiety disorders is well demonstrated. However, only three studies point to the efficacy of systemic therapy (ST) in anxiety disorders, and only two of them especially focus on social anxiety disorders. These ST studies either do not use a good comparator but minimal supportive therapy, they do not use a multi-person ST but a combined therapy, or they do not especially focus on social anxiety disorders but mood and anxiety disorders in general. Though ST was approved as evidence based in Germany for a variety of disorders in 2008, evidence did not include anxiety disorders. This is the first pilot study that will investigate multi-person ST, integrating a broad range of systemic methods, specifically for social anxiety disorders and that will compare ST to the "gold standard" CBT. This article describes the rationale and protocol of a prospective, open, interventive, balanced, bi-centric, pilot randomized controlled trial (RCT). A total of 32 patients with a primary SCID diagnosis of social anxiety disorder will be randomized to either CBT or ST. Both treatments will be manualized. The primary outcome will include social anxiety symptoms at the end of therapy. Therapy will be restricted to no more than 26 hours (primary endpoint). Secondary outcomes will include psychological, social systems and interpersonal functioning, symptom adjustment, and caregiver burden, in addition to change measures, therapist variables and treatment adherence. At the secondary endpoints, 9 and 12 months after the beginning of therapy, we will again assess all outcomes. The study is expected to pilot test a RCT which will be the first to directly compare CBT and multi-person ST, integrating a broad range of systemic methods, for social anxiety disorders, and it will provide empirical evidence for the calculation of the number of patients needed for a confirmatory RCT. ClinicalTrials.gov: NCT02360033 ; date of registration: 21 January 2015.

Nanomedicine for prostate cancer using nanoemulsion: A review.

PubMed

Sasikumar, Aravindsiva; Kamalasanan, Kaladhar

2017-08-28

Prostate cancer (PCa) is a worldwide issue, with burgeoning rise in prevalence, morbidity and mortality. Targeted drug delivery, a long sort solution in this regard using controlled release (CR) - nanocarriers, is still a challenge. There is an emerging criticism that, the challenges are due to less appreciation for the biological barriers and lack of corresponding newer technologies. Over the years, more understanding about the biological barriers has come with the progress in characterization techniques. Correspondingly, there is a change in opinion about approaches in clinical trial that; focus of the end point need to be shifted towards disease stabilization for these explorative technologies. Currently, there is a requirement to overcome these newly identified challenges to develop newer affordable therapeutics. The ongoing clinical protocol for therapy using CR-nanocarriers is intravenous injection followed by local targeting to cancer site. This is the most accepted protocol and new CR-nanocarriers are being developed to suit this protocol. In this review, recent progress in treatment of PCa using CR-nanocarriers is analyzed with respect to newly identified biological barriers and design challenges. Possibilities of exploring nanoemulsion (NE) platform for targeted drug delivery to PCa are examined. Repurposing of drugs and combination therapy using NE platform targeted to PCa can be explored for design and development of affordable nanomedicine. In 20yrs. from now there expected to be numerous affordable nanomedicine technologies available in market exploring these lines. Copyright © 2017 Elsevier B.V. All rights reserved.

Drug delivery optimization through Bayesian networks.

PubMed Central

Bellazzi, R.

1992-01-01

This paper describes how Bayesian Networks can be used in combination with compartmental models to plan Recombinant Human Erythropoietin (r-HuEPO) delivery in the treatment of anemia of chronic uremic patients. Past measurements of hematocrit or hemoglobin concentration in a patient during the therapy can be exploited to adjust the parameters of a compartmental model of the erythropoiesis. This adaptive process allows more accurate patient-specific predictions, and hence a more rational dosage planning. We describe a drug delivery optimization protocol, based on our approach. Some results obtained on real data are presented. PMID:1482938

Multidrug-resistant bacteria in hematology patients: emerging threats.

PubMed

Tatarelli, Paola; Mikulska, Malgorzata

2016-06-01

Multidrug-resistant (MDR) bacteria, particularly Gram negatives, such as Enterobacteriaceae resistant to third-generation cephalosporins or carbapenems and MDR Pseudomonas aeruginosa, are increasingly frequent in hematology patients. The prevalence of different resistant species varies significantly between centers. Thus, the knowledge of local epidemiology is mandatory for deciding the most appr-opriate management protocols. In the era of increasing antibiotic resistance, empirical therapy of febrile neutropenia should be individualized. A de-escalation approach is recommended in case of severe clinical presentation in patients who are at high risk for infection with a resistant strain. Targeted therapy of an MDR Gram negative usually calls for a combination treatment, although no large randomized trials exist in this setting. Infection control measures are the cornerstone of limiting the spread of MDR pathogens in hematology units.

The Integration of Family and Group Therapy as an Alternative to Juvenile Incarceration: A Quasi-Experimental Evaluation Using Parenting with Love and Limits.

PubMed

Karam, Eli A; Sterrett, Emma M; Kiaer, Lynn

2017-06-01

The current study employed a quasi-experimental design using both intent-to-treat and protocol adherence analysis of 155 moderate- to high-risk juvenile offenders to evaluate the effectiveness of Parenting with Love and Limits® (PLL), an integrative group and family therapy approach. Youth completing PLL had significantly lower rates of recidivism than the comparison group. Parents also reported statistically significant improvements in youth behavior. Lengths of service were also significantly shorter for the treatment sample than the matched comparison group by an average of 4 months. This study contributes to the literature by suggesting that intensive community-based combined family and group treatment is effective in curbing recidivism among high-risk juveniles. © 2015 Family Process Institute.

Comparison of the pharmacokinetics between L-BPA and L-FBPA using the same administration dose and protocol: a validation study for the theranostic approach using [18F]-L-FBPA positron emission tomography in boron neutron capture therapy.

PubMed

Watanabe, Tsubasa; Hattori, Yoshihide; Ohta, Youichiro; Ishimura, Miki; Nakagawa, Yosuke; Sanada, Yu; Tanaka, Hiroki; Fukutani, Satoshi; Masunaga, Shin-Ichiro; Hiraoka, Masahiro; Ono, Koji; Suzuki, Minoru; Kirihata, Mitsunori

2016-11-08

Boron neutron capture therapy (BNCT) is a cellular-level particle radiation therapy that combines the selective delivery of boron compounds to tumour tissue with neutron irradiation. L-p-Boronophenylalanine (L-BPA) is a boron compound now widely used in clinical situations. Determination of the boron distribution is required for successful BNCT prior to neutron irradiation. Thus, positron emission tomography with [ 18 F]-L-FBPA, an 18 F-labelled radiopharmaceutical analogue of L-BPA, was developed. However, several differences between L-BPA and [ 18 F]-L-FBPA have been highlighted, including the different injection doses and administration protocols. The purpose of this study was to clarify the equivalence between L-BPA and [ 19 F]-L-FBPA as alternatives to [ 18 F]-L-FBPA. SCC-VII was subcutaneously inoculated into the legs of C3H/He mice. The same dose of L-BPA or [ 19 F]-L-FBPA was subcutaneously injected. The time courses of the boron concentrations in blood, tumour tissue, and normal tissue were compared between the groups. Next, we administered the therapeutic dose of L-BPA or the same dose of [ 19 F]-L-FBPA by continuous infusion and compared the effects of the administration protocol on boron accumulation in tissues. There were no differences between L-BPA and [ 19 F]-L-FBPA in the transition of boron concentrations in blood, tumour tissue, and normal tissue using the same administration protocol. However, the normal tissue to blood ratio of the boron concentrations in the continuous-infusion group was lower than that in the subcutaneous injection group. No difference was noted in the time course of the boron concentrations in tumour tissue and normal tissues between L-BPA and [ 19 F]-L-FBPA. However, the administration protocol had effects on the normal tissue to blood ratio of the boron concentration. In estimating the BNCT dose in normal tissue by positron emission tomography (PET), we should consider the possible overestimation of the normal tissue to blood ratio of the boron concentrations derived from the values measured by PET on dose calculation.

Treatment effects of massage therapy in depressed people: a meta-analysis.

PubMed

Hou, Wen-Hsuan; Chiang, Pai-Tsung; Hsu, Tun-Yen; Chiu, Su-Ying; Yen, Yung-Chieh

2010-07-01

To systematically investigate the treatment effects of massage therapy in depressed people by incorporating data from recent studies. A meta-analysis of randomized controlled trials (RCTs) of massage therapy in depressed people was conducted using published studies from PubMed, EMBASE, PsycINFO, and CINAHL electronic database from inception until July 2008. The terms used for the search were derived from medical subheading term (MeSH) massage combined with MeSH depression. Hand searching was also checked for bibliographies of relevant articles. Retrieval articles were constrained to RCTs/clinical trials and human subjects. No language restrictions were imposed. We included 17 studies containing 786 persons from 246 retrieved references. Trials with other intervention, combined therapy, and massage on infants or pregnant women were excluded. Two reviewers independently performed initial screen and assessed quality indicators by Jadad scale. Data were extracted on publication year, participant characteristics, and outcomes by another single reviewer. All trials showed positive effect of massage therapy on depressed people. Seventeen RCTs were of moderate quality, with a mean quality score of 6.4 (SD = 0.85). The pooled standardized mean difference in fixed- and random-effects models were 0.76 (95% CI, 0.61-0.91) and 0.73 (95% CI, 0.52-0.93), respectively. Both indicated significant effectiveness in the treatment group compared with the control group. The variance between these studies revealed possible heterogeneity (tau(2) = 0.06, Cochran chi-squared(16) = 25.77, P = .06). Massage therapy is significantly associated with alleviated depressive symptoms. However, standardized protocols of massage therapy, various depression rating scales, and target populations in further studies are suggested. (c) Copyright 2010 Physicians Postgraduate Press, Inc.

Changes in co-contraction during stair descent after manual therapy protocol in knee osteoarthritis: A pilot, single-blind, randomized study.

PubMed

Cruz-Montecinos, Carlos; Flores-Cartes, Rodrigo; Montt-Rodriguez, Agustín; Pozo, Esteban; Besoaín-Saldaña, Alvaro; Horment-Lara, Giselle

2016-10-01

Manual therapy has shown clinical results in patients with knee osteoarthritis. However, the biomechanical aspects during functional tasks have not been explored in depth. Through surface electromyography, the medial and lateral co-contractions of the knee were measured while descending stairs, prior and posterior to applying a manual therapy protocol in the knee, with emphasis on techniques of joint mobilization and soft-tissue management. Sixteen females with slight or moderate knee osteoarthritis were recruited (eight experimental, eight control). It was observed that the lateral co-contraction index of the experimental group, posterior to intervention, increased by 11.7% (p = 0.014). The application of a manual therapy protocol with emphasis on techniques of joint mobilization and soft-tissue management modified lateral co-contraction, which would have a protective effect on the joint. Copyright © 2016 Elsevier Ltd. All rights reserved.

Efficacy of combined conservative therapies on clinical outcomes in patients with thumb base osteoarthritis: protocol for a randomised, controlled trial (COMBO).

PubMed

Deveza, Leticia A; Hunter, David J; Wajon, Anne; Bennell, Kim L; Vicenzino, Bill; Hodges, Paul; Eyles, Jillian P; Jongs, Ray; Riordan, Edward A; Duong, Vicky; Min Oo, Win; O'Connell, Rachel; Meneses, Sarah R F

2017-01-12

Management of thumb base osteoarthritis (OA) using a combination of therapies is common in clinical practice; however, evidence for the efficacy of this approach is lacking. The aim of this study is to determine the effect of a combination of conservative therapies for the treatment of thumb base OA compared with an education control group. This is a randomised, controlled, single-centre, two-arm superiority trial with 1:1 allocation ratio; with assessor and statistician blinded. Participants are blinded to the trial's hypothesis and to the interventions received by the opposite group. A total of 204 participants will be recruited from the community and randomised using a computer-generated schedule. The intervention group will receive education for joint protection and OA, a splint for the base of the thumb, hand exercises and topical diclofenac sodium 1% gel over 6 weeks. The control group will receive education for joint protection and OA alone. Main inclusion criteria are pain ≥40 mm (Visual Analogue Scale, 0-100) at the base of the thumb, impairment in hand function ≥6 (Functional Index for Hand Osteoarthritis, 0-30) and radiographic thumb base OA (Kellgren Lawrence grade ≥2). Participants currently receiving any of the intervention components will be excluded. Outcomes will be measured at 2, 6 and 12 weeks. The primary outcome is change in pain and hand function from baseline to 6 weeks. Other outcomes include changes in grip and pinch strength, quality of life, presence of joint swelling and tenderness, duration of joint stiffness, patient's global assessment and use of rescue medication. Analysis will be performed according to the intention-to-treat principle. Adverse events will be monitored throughout the study. This protocol is approved by the local ethics committee (HREC/15/HAWKE/479). Dissemination will occur through presentations at international conferences and publication in peer-reviewed journals. ACTRN12616000353493; Pre-results. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Substance Abuse Treatment: Group Therapy. Treatment Improvement Protocol (TIP) Series 41

ERIC Educational Resources Information Center

Gilbert, Jonathan Max; Hills, Susan; Rife, Mary Lou

2005-01-01

This Treatment Improvement Protocol (TIP) presents an overview of the role and efficacy of group therapy in substance abuse treatment. TIPs are best-practice guidelines for the treatment of substance use disorders that make the latest research in substance abuse treatment available to counselors and educators. The content was generated by a panel…

Substance Abuse Treatment And Family Therapy. A Treatment Improvement Protocol (TIP) Series 39

ERIC Educational Resources Information Center

Gilbert, Jonathan Max; Oliff, Helen; Sutton, David; Bartlett, Catalina; Henderson, Randi

2004-01-01

This Treatment Improvement Protocol (TIP) addresses substance abuse treatment in the context of family therapy. TIPs are best-practice guidelines for the treatment of substance use disorders that make the latest research in substance abuse treatment available to counselors and educators. The content was generated by a panel of experts in the…

Combined intravitreal bevacizumab and photodynamic therapy with vertiporfin for management of choroidal neovascularization secondary to age-related macular degeneration

PubMed Central

Kabeel, Mamdouh M; El-Batarny, Ashraf M; Tameesh, Mohamed K; Abou El Enein, Moustafa A

2008-01-01

Purpose To test the results for patients treated with combined photodynamic therapy (PDT) with vertiporfin (Visudyne, Novartis AG) and intravitreal bevacizumab for choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD). Patients and methods This is a prospective study including 18 eyes with subfoveal or juxtafoveal CNV secondary to AMD. Patients were treated with intravitreal bevacizumab 2.5 mg in the morning then PDT with vertiporfin in the evening of the same day. All patients were followed up for 6 months. The main outcome measures were stabilization (no change) or improvement of best corrected visual acuity (BCVA) with no leakage in fluorescein angiography (FLA) and reduction of central retinal thickness, and retreatment rate. Results At the end of 6 months follow up, all cases had either stabilization or improved BCVA. Fifteen eyes (80%) showed improved BCVA. The overall mean improvement in BCVA (n = 18) was 2.17 lines. Fifteen eyes (80%) required single combined treatment. Only 3 eyes (20%) required retreatment with the same protocol. No systemic or ocular complications were reported. Conclusion Combined intravitreal bevacizumab and PDT as a treatment of CNV secondary to AMD either for predominantly classic or occult subtypes has a positive therapeutic effect with stabilization or improvement of final BCVA and also might reduce the need for retreatment compared with literature retreatment rates of either modality alone. Summary Eighteen patients receiving combined therapy with PDT and intravitreal bevacizumab for CNV secondary to AMD, showed not only significant visual improvement but also reduction in the frequency of retreatment when compared to the results of monotherapy with each modality. PMID:19668400

Evaluation of current trends and recent development in insulin therapy for management of diabetes mellitus.

PubMed

Nawaz, Muhammad Sarfraz; Shah, Kifayat Ullah; Khan, Tahir Mehmood; Rehman, Asim Ur; Rashid, Haroon Ur; Mahmood, Sajid; Khan, Shahzeb; Farrukh, Muhammad Junaid

2017-12-01

Diabetes mellitus is a major health problem in developing countries. There are various insulin therapies to manage diabetes mellitus. This systematic review evaluates various insulin therapies for management of diabetes mellitus worldwide. This review also focuses on recent developments being explored for better management of diabetes mellitus. We reviewed a number of published articles from 2002 to 2016 to find out the appropriate management of diabetes mellitus. The paramount parameters of the selected studies include the insulin type & its dose, type of diabetes, duration and comparison of different insulin protocols. In addition, various newly developed approaches for insulin delivery with potential output have also been evaluated. A great variability was observed in managing diabetes mellitus through insulin therapy and the important controlling factors found for this therapy include; dose titration, duration of insulin use, type of insulin used and combination therapy of different insulin. A range of research articles on current trends and recent advances in insulin has been summarized, which led us to the conclusion that multiple daily insulin injections or continuous subcutaneous insulin infusion (insulin pump) is the best method to manage diabetes mellitus. In future perspectives, development of the oral and inhalant insulin would be a tremendous breakthrough in Insulin therapy. Copyright © 2017 Diabetes India. Published by Elsevier Ltd. All rights reserved.

Systematic Review of the Effectiveness of Physical Therapy Modalities in Women With Provoked Vestibulodynia.

PubMed

Morin, Mélanie; Carroll, Marie-Soleil; Bergeron, Sophie

2017-07-01

Pelvic floor muscle physical therapy is recommended in clinical guidelines for women with provoked vestibulodynia (PVD). Including isolated or combined treatment modalities, physical therapy is viewed as an effective first-line intervention, yet no systematic review concerning the effectiveness of physical therapy has been conducted. To systematically appraise the current literature on the effectiveness of physical therapy modalities for decreasing pain during intercourse and improving sexual function in women with PVD. A systematic literature search using PubMed, Scopus, CINHAL, and PEDro was conducted until October 2016. Moreover, a manual search from reference lists of included articles was performed. Ongoing trials also were reviewed using clinicaltrial.gov and ISRCTNregistry. Randomized controlled trials, prospective and retrospective cohorts, and case reports evaluating the effect of isolated or combined physical therapy modalities in women with PVD were included in the review. Main outcome measures were pain during intercourse, sexual function, and patient's perceived improvement. The literature search resulted in 43 eligible studies including 7 randomized controlled trials, 20 prospective studies, 5 retrospective studies, 6 case reports, and 6 study protocols. Most studies had a high risk of bias mainly associated with the lack of a comparison group. Another common bias was related to insufficient sample size, non-validated outcomes, non-standardized intervention, and use of other ongoing treatment. The vast majority of studies showed that physical therapy modalities such as biofeedback, dilators, electrical stimulation, education, multimodal physical therapy, and multidisciplinary approaches were effective for decreasing pain during intercourse and improving sexual function. The positive findings for the effectiveness of physical therapy modalities in women with PVD should be investigated further in robust and well-designed randomized controlled trials. Morin M, Carroll M-S, Bergeron S. Systematic Review of the Effectiveness of Physical Therapy Modalities in Women With Provoked Vestibulodynia. Sex Med Rev 2017;5:295-322. Copyright © 2017 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.

A Look to Future Directions in Gene Therapy Research for Monogenic Diseases

PubMed Central

Porteus, Matthew H; Connelly, Jon P; Pruett, Shondra M

2006-01-01

The concept of gene therapy has long appealed to biomedical researchers and clinicians because it promised to treat certain diseases at their origins. In the last several years, there have been several trials in which patients have benefited from gene therapy protocols. This progress, however, has revealed important problems, including the problem of insertional oncogenesis. In this review, which focuses on monogenic diseases, we discuss the problem of insertional oncogenesis and identify areas for future research, such as developing more quantitative assays for risk and efficacy, and ways of minimizing the genotoxic effects of gene therapy protocols, which will be important if gene therapy is to fulfill its conceptual promise. PMID:17009872

Importance of Standardized DXA Protocol for Assessing Physique Changes in Athletes.

PubMed

Nana, Alisa; Slater, Gary J; Hopkins, Will G; Halson, Shona L; Martin, David T; West, Nicholas P; Burke, Louise M

2016-06-01

The implications of undertaking DXA scans using best practice protocols (subjects fasted and rested) or a less precise but more practical protocol in assessing chronic changes in body composition following training and a specialized recovery technique were investigated. Twenty-one male cyclists completed an overload training program, in which they were randomized to four sessions per week of either cold water immersion therapy or control groups. Whole-body DXA scans were undertaken with best practice protocol (Best) or random activity protocol (Random) at baseline, after 3 weeks of overload training, and after a 2-week taper. Magnitudes of changes in total, lean and fat mass from baseline-overload, overload-taper and baseline-taper were assessed by standardization (Δmean/SD). The standard deviations of change scores for total and fat-free soft tissue mass (FFST) from Random scans (2-3%) were approximately double those observed in the Best (1-2%), owing to extra random errors associated with Random scans at baseline. There was little difference in change scores for fat mass. The effect of cold water immersion therapy on baseline-taper changes in FFST was possibly harmful (-0.7%; 90% confidence limits ±1.2%) with Best scans but unclear with Random scans (0.9%; ±2.0%). Both protocols gave similar possibly harmful effects of cold water immersion therapy on changes in fat mass (6.9%; ±13.5% and 5.5%; ±14.3%, respectively). An interesting effect of cold water immersion therapy on training-induced changes in body composition might have been missed with a less precise scanning protocol. DXA scans should be undertaken with Best.

EON: a component-based approach to automation of protocol-directed therapy.

PubMed Central

Musen, M A; Tu, S W; Das, A K; Shahar, Y

1996-01-01

Provision of automated support for planning protocol-directed therapy requires a computer program to take as input clinical data stored in an electronic patient-record system and to generate as output recommendations for therapeutic interventions and laboratory testing that are defined by applicable protocols. This paper presents a synthesis of research carried out at Stanford University to model the therapy-planning task and to demonstrate a component-based architecture for building protocol-based decision-support systems. We have constructed general-purpose software components that (1) interpret abstract protocol specifications to construct appropriate patient-specific treatment plans; (2) infer from time-stamped patient data higher-level, interval-based, abstract concepts; (3) perform time-oriented queries on a time-oriented patient database; and (4) allow acquisition and maintenance of protocol knowledge in a manner that facilitates efficient processing both by humans and by computers. We have implemented these components in a computer system known as EON. Each of the components has been developed, evaluated, and reported independently. We have evaluated the integration of the components as a composite architecture by implementing T-HELPER, a computer-based patient-record system that uses EON to offer advice regarding the management of patients who are following clinical trial protocols for AIDS or HIV infection. A test of the reuse of the software components in a different clinical domain demonstrated rapid development of a prototype application to support protocol-based care of patients who have breast cancer. PMID:8930854

Structured Counseling for Auditory Dynamic Range Expansion.

PubMed

Gold, Susan L; Formby, Craig

2017-02-01

A structured counseling protocol is described that, when combined with low-level broadband sound therapy from bilateral sound generators, offers audiologists a new tool for facilitating the expansion of the auditory dynamic range (DR) for loudness. The protocol and its content are specifically designed to address and treat problems that impact hearing-impaired persons who, due to their reduced DRs, may be limited in the use and benefit of amplified sound from hearing aids. The reduced DRs may result from elevated audiometric thresholds and/or reduced sound tolerance as documented by lower-than-normal loudness discomfort levels (LDLs). Accordingly, the counseling protocol is appropriate for challenging and difficult-to-fit persons with sensorineural hearing losses who experience loudness recruitment or hyperacusis. Positive treatment outcomes for individuals with the former and latter conditions are highlighted in this issue by incremental shifts (improvements) in LDL and/or categorical loudness judgments, associated reduced complaints of sound intolerance, and functional improvements in daily communication, speech understanding, and quality of life leading to improved hearing aid benefit, satisfaction, and aided sound quality, posttreatment.

Structured Counseling for Auditory Dynamic Range Expansion

PubMed Central

Gold, Susan L.; Formby, Craig

2017-01-01

A structured counseling protocol is described that, when combined with low-level broadband sound therapy from bilateral sound generators, offers audiologists a new tool for facilitating the expansion of the auditory dynamic range (DR) for loudness. The protocol and its content are specifically designed to address and treat problems that impact hearing-impaired persons who, due to their reduced DRs, may be limited in the use and benefit of amplified sound from hearing aids. The reduced DRs may result from elevated audiometric thresholds and/or reduced sound tolerance as documented by lower-than-normal loudness discomfort levels (LDLs). Accordingly, the counseling protocol is appropriate for challenging and difficult-to-fit persons with sensorineural hearing losses who experience loudness recruitment or hyperacusis. Positive treatment outcomes for individuals with the former and latter conditions are highlighted in this issue by incremental shifts (improvements) in LDL and/or categorical loudness judgments, associated reduced complaints of sound intolerance, and functional improvements in daily communication, speech understanding, and quality of life leading to improved hearing aid benefit, satisfaction, and aided sound quality, posttreatment. PMID:28286367

Comparison of Haloperidol Alone and in Combination with Midazolam for the Treatment of Acute Agitation in an Inpatient Palliative Care Service.

PubMed

Ferraz Gonçalves, José António; Almeida, Ana; Costa, Isabel; Silva, Paula; Carneiro, Rui

2016-12-01

Agitation is a very distressing problem that must be controlled as quickly as possible, but using a safe method. The authors conducted a comparison of two protocols: a combination of haloperidol and midazolam and haloperidol alone. The combination drug protocol controlled 101 out of 121 (84%) episodes of agitation with only the first dose, whereas the haloperidol alone protocol controlled 47 out of 74 (64%) episodes. This difference is statistically significant (P =.002), with a post hoc analyzed power of 0.88. The median time from the first dose to the control of agitation was 15 minutes (range: 5-210) with the combination and 60 minutes (range: 10-430) with the other protocol, P <.001. There were no complications other than some transient somnolence, mainly with the combination protocol. The authors conclude that the combination of haloperidol and midazolam is effective and safe for the control of agitation in palliative care and it is more effective than haloperidol alone. Therefore, the combination should be adopted as the preferred protocol. It would be helpful if the usefulness of this protocol is confirmed by others.

The application of antimicrobial photodynamic therapy (aPDT) in dentistry: a critical review

PubMed Central

Carrera, E T; Dias, H B; Corbi, S C T; Marcantonio, R A C; Bernardi, A C A; Bagnato, V S; Hamblin, M R; Rastelli, A N S

2017-01-01

In recent years there have been an increasing number of in vitro and in vivo studies that show positive results regarding antimicrobial photodynamic therapy (aPDT) used in dentistry. These include applications in periodontics, endodontics, and mucosal infections caused by bacteria present as biofilms. Antimicrobial photodynamic therapy is a therapy based on the combination of a non-toxic photosensitizer (PS) and appropriate wavelength visible light, which in the presence of oxygen is activated to produce reactive oxygen species (ROS). ROS induce a series of photochemical and biological events that cause irreversible damage leading to the death of microorganisms. Many light-absorbing dyes have been mentioned as potential PS for aPDT and different wavelengths have been tested. However, there is no consensus on a standard protocol yet. Thus, the goal of this review was to summarize the results of research on aPDT in dentistry using the PubMed database focusing on recent studies of the effectiveness aPDT in decreasing microorganisms and microbial biofilms, and also to describe aPDT effects, mechanisms of action and applications. PMID:29151775

Estimating Tissue Iron Burden: Current Status and Future Prospects

PubMed Central

Wood, John C.

2015-01-01

SUMMARY Iron overload is becoming an increasing problem as haemoglobinopathy patients gain greater access to good medical care and as therapies for myelodysplastic syndromes improve. Therapeutic options for iron chelation therapy have increased and many patients now receive combination therapies. However, optimal utilization of iron chelation therapy requires knowledge not only of the total body iron burden but the relative iron distribution among the different organs. The physiological basis for extrahepatic iron deposition is presented in order to help identify patients at highest risk for cardiac and endocrine complications. This manuscript reviews the current state of the art for monitoring global iron overload status as well as its compartmentalization. Plasma markers, computerized tomography, liver biopsy, magnetic susceptibility devices and magnetic resonance imaging (MRI) techniques are all discussed but MRI has come to dominate clinical practice. The potential impact of recent pancreatic and pituitary MRI studies on clinical practice are discussed as well as other works-in-progress. Clinical protocols are derived from experience in haemoglobinopathies but may provide useful guiding principles for other iron overload disorders, such as myelodysplastic syndromes. PMID:25765344

The application of antimicrobial photodynamic therapy (aPDT) in dentistry: a critical review

NASA Astrophysics Data System (ADS)

Carrera, E. T.; Dias, H. B.; Corbi, S. C. T.; Marcantonio, R. A. C.; Bernardi, A. C. A.; Bagnato, V. S.; Hamblin, M. R.; Rastelli, A. N. S.

2016-12-01

In recent years there have been an increasing number of in vitro and in vivo studies that show positive results regarding antimicrobial photodynamic therapy (aPDT) used in dentistry. These include applications in periodontics, endodontics, and mucosal infections caused by bacteria present as biofilms. Antimicrobial photodynamic therapy is a therapy based on the combination of a non-toxic photosensitizer (PS) and appropriate wavelength visible light, which in the presence of oxygen is activated to produce reactive oxygen species (ROS). ROS induce a series of photochemical and biological events that cause irreversible damage leading to the death of microorganisms. Many light-absorbing dyes have been mentioned as potential PS for aPDT and different wavelengths have been tested. However, there is no consensus on a standard protocol yet. Thus, the goal of this review was to summarize the results of research on aPDT in dentistry using the PubMed database focusing on recent studies of the effectiveness aPDT in decreasing microorganisms and microbial biofilms, and also to describe aPDT effects, mechanisms of action and applications.

Hyperbaric Oxygen as Radiation Sensitizer for Locally Advanced Squamous Cell Carcinoma of the Oropharynx: A Phase 1 Dose-Escalation Study.

PubMed

Hartford, Alan C; Davis, Thomas H; Buckey, Jay C; Foote, Robert L; Sinesi, Mark S; Williams, Benjamin B; Fariss, Anna K; Schaner, Philip E; Claus, Paul L; Okuno, Scott H; Hussey, James R; Clarke, Richard E

2017-03-01

To explore, in a dose-escalation study, the feasibility of hyperbaric oxygen (HBO) treatments immediately before intensity modulated radiation therapy in conjunction with cisplatinum chemotherapy for squamous cell carcinoma of the head and neck (SCCHN). Eligible patients presented with SCCHN (stage III-IV [M0]), life expectancy >6 months, and Karnofsky performance status ≥70. Enrollees received intensity modulated radiation therapy, 70 Gy in 35 fractions over 7 weeks with weekly cisplatinum. Patients received HBO-100% oxygen, 2.4 atmospheres absolute (ATA) for 30 minutes-twice per week initially. Subsequent patients were escalated to 3 and then 5 times per week. Intensity modulated radiation therapy began within 15 minutes after HBO. Patients were followed for 2 years after RT with quality-of-life questionnaires (Performance Status Scale-Head and Neck Cancer and the Functional Assessment of Cancer Therapy-Head and Neck Cancer) and for 5+ years for local recurrence, distant metastases, disease-specific survival, and overall survival. Twelve subjects enrolled from 3 centers. Two withdrew during radiation therapy and 1 within 14 weeks after radiation therapy. The remaining 9 had primary oropharyngeal disease and were stage IVA (7) or IVB (2). No dose-limiting toxicities were observed with daily HBO. Two patients (22%) required pressure equalization tubes. The average time between HBO and radiation therapy was 8.5 minutes, with 2 of 231 administrations delivered beyond 15 minutes (0.5%). Per-protocol analysis showed a clinical complete response in 7 and a pathologic complete response without tumor in salvage neck dissections in 2. With minimum follow-up of 61 months, per-protocol 5-year overall survival was 100%, local recurrence 0%, and distant metastases 11%. Patient-reported outcomes for quality of life (Functional Assessment of Cancer Therapy-Head and Neck Cancer) were comparable to published results for chemoradiotherapy without HBO. While acknowledging the study's small size and early attrition of 3 patients, our in-depth review of the acquired data indicates the feasibility of combining HBO with chemoradiation. Copyright © 2016 Elsevier Inc. All rights reserved.

Rabeprazole, Minocycline, Amoxicillin, and Bismuth as First-Line and Second-Line Regimens for Helicobacter pylori Eradication.

PubMed

Song, Zhiqiang; Suo, Baojun; Zhang, Lingyun; Zhou, Liya

2016-12-01

Because of general unavailability of tetracycline, common adverse effects, and complicated administration, the clinical application of bismuth quadruple therapy often faces difficulties. Whether the combination of minocycline and amoxicillin can replace tetracycline and metronidazole for Helicobacter pylori eradication remains unclear. This study was to determine the efficacy, compliance, and safety of rabeprazole, minocycline, amoxicillin, and bismuth (RMAB) therapy as first-line and second-line regimens. Between July 2013 and December 2015, a total of 160 patients in first-line and 70 patients in second-line therapies received rabeprazole 10 mg, minocycline 100 mg, amoxicillin 1000 mg, and bismuth potassium citrate 220 mg twice daily for 14 days. Eradication status was assessed 6-12 weeks after treatment. RMAB therapy achieved the eradication rates of 87.5% (95% confidence interval, 81.9-92.5%, intention-to-treat analysis), 90.9% (85.7-95.5%, modified intention-to-treat analysis), and 92.6% (88.5-96.6%, per-protocol analysis) in first-line therapy in a setting with high antibiotic resistance rates (amoxicillin 3.4%, clarithromycin 39.7%, metronidazole 60.3%, levofloxacin 36.2%, tetracycline 3.4%, and minocycline 6.9%). As for second-line therapy, the eradication rates were 82.9% (74.3-91.4%, intention-to-treat analysis), 86.6% (77.6-94.0%, modified intention-to-treat analysis), and 89.1% (81.3-95.3%, per-protocol analysis). Totally, 24.0% patients had adverse effects, 2.2% discontinued medications, and good compliance was achieved in 94.7%. Poor compliance and minocycline resistance were identified as the risk factors for treatment failure. Significant differences in efficacy existed among the groups of both sensitive (48/51 and 18/20), isolated amoxicillin resistance (1/1 and 0/0), isolated minocycline resistance (2/3 and 1/1), and dual resistance (0/1 and 0/1) in both first-line (p = .004) and second-line (p = .035) therapies. The eradication efficacies of RMAB therapy as first-line and second-line regimens were satisfactory with good compliance and safety in a region with high antibiotic resistance. © 2016 John Wiley & Sons Ltd.

Ten good reasons to practice ultrasound in critical care.

PubMed

Lichtenstein, Daniel; van Hooland, Simon; Elbers, Paul; Malbrain, Manu L N G

2014-01-01

Over the past decade, critical care ultrasound has gained its place in the armamentarium of monitoring tools. A greater understanding of lung, abdominal, and vascular ultrasound plus easier access to portable machines have revolutionised the bedside assessment of our ICU patients. Because ultrasound is not only a diagnostic test, but can also be seen as a component of the physical exam, it has the potential to become the stethoscope of the 21st century. Critical care ultrasound is a combination of simple protocols, with lung ultrasound being a basic application, allowing assessment of urgent diagnoses in combination with therapeutic decisions. The LUCI (Lung Ultrasound in the Critically Ill) consists of the identification of ten signs: the bat sign (pleural line); lung sliding (seashore sign); the A-lines (horizontal artefact); the quad sign and sinusoid sign indicating pleural effusion; the fractal and tissue-like sign indicating lung consolidation; the B-lines and lung rockets indicating interstitial syndromes; abolished lung sliding with the stratosphere sign suggesting pneumothorax; and the lung point indicating pneumothorax. Two more signs, the lung pulse and the dynamic air bronchogram, are used to distinguish atelectasis from pneumonia. The BLUE protocol (Bedside Lung Ultrasound in Emergency) is a fast protocol (< 3 minutes), also including a vascular (venous) analysis allowing differential diagnosis in patients with acute respiratory failure. With this protocol, it becomes possible to differentiate between pulmonary oedema, pulmonary embolism, pneumonia, chronic obstructive pulmonary disease, asthma, and pneumothorax, each showing specific ultrasound patterns and profiles. The FALLS protocol (Fluid Administration Limited by Lung Sonography) adapts the BLUE protocol to be used in patients with acute circulatory failure. It makes a sequential search for obstructive, cardiogenic, hypovolemic, and distributive shock using simple real-time echocardiography in combination with lung ultrasound, with the appearance of B-lines considered to be the endpoint for fluid therapy. An advantage of lung ultrasound is that the patient is not exposed to radiation, and so the LUCI-FLR project (LUCI favouring limitation of radiation) can be unfolded in trauma patients. Although it has been practiced for 25 years, critical care ultrasound is a relatively young but expanding discipline and can be seen as the stethoscope of the modern intensivist. In this review, the usefulness and advantages of ultrasound in the critical care setting are discussed in ten points. The emphasis is on a holistic approach, with a central role for lung ultrasound.

"Check, Change What You Need to Change and/or Keep What You Want": An Art Therapy Neurobiological-Based Trauma Protocol

ERIC Educational Resources Information Center

Hass-Cohen, Noah; Clyde Findlay, Joanna; Carr, Richard; Vanderlan, Jessica

2014-01-01

The Check ("Check, Change What You Need To Change and/or Keep What You Want") art therapy protocol is a sequence of directives for treating trauma that is grounded in neurobiological theory and designed to facilitate trauma narrative processing, autobiographical coherency, and the rebalancing of dysregulated responses to psychosocial…

An international dosimetry exchange for boron neutron capture therapy. Part I: Absorbed dose measurements.

PubMed

Binns, P J; Riley, K J; Harling, O K; Kiger, W S; Munck af Rosenschöld, P M; Giusti, V; Capala, J; Sköld, K; Auterinen, I; Serén, T; Kotiluoto, P; Uusi-Simola, J; Marek, M; Viererbl, L; Spurny, F

2005-12-01

An international collaboration was organized to undertake a dosimetry exchange to enable the future combination of clinical data from different centers conducting neutron capture therapy trials. As a first step (Part I) the dosimetry group from the Americas, represented by MIT, visited the clinical centers at Studsvik (Sweden), VTT Espoo (Finland), and the Nuclear Research Institute (NRI) at Rez (Czech Republic). A combined VTT/NRI group reciprocated with a visit to MIT. Each participant performed a series of dosimetry measurements under equivalent irradiation conditions using methods appropriate to their clinical protocols. This entailed in-air measurements and dose versus depth measurements in a large water phantom. Thermal neutron flux as well as fast neutron and photon absorbed dose rates were measured. Satisfactory agreement in determining absorbed dose within the experimental uncertainties was obtained between the different groups although the measurement uncertainties are large, ranging between 3% and 30% depending upon the dose component and the depth of measurement. To improve the precision in the specification of absorbed dose amongst the participants, the individually measured dose components were normalized to the results from a single method. Assuming a boron concentration of 15 microg g(-1) that is typical of concentrations realized clinically with the boron delivery compound boronophenylalanine-fructose, systematic discrepancies in the specification of the total biologically weighted dose of up to 10% were apparent between the different groups. The results from these measurements will be used in future to normalize treatment plan calculations between the different clinical dosimetry protocols as Part II of this study.

Theranostic Imaging of Cancer Gene Therapy.

PubMed

Sekar, Thillai V; Paulmurugan, Ramasamy

2016-01-01

Gene-directed enzyme prodrug therapy (GDEPT) is a promising therapeutic approach for treating cancers of various phenotypes. This strategy is independent of various other chemotherapeutic drugs used for treating cancers where the drugs are mainly designed to target endogenous cellular mechanisms, which are different in various cancer subtypes. In GDEPT an external enzyme, which is different from the cellular proteins, is expressed to convert the injected prodrug in to a toxic metabolite, that normally kill cancer cells express this protein. Theranostic imaging is an approach used to directly monitor the expression of these gene therapy enzymes while evaluating therapeutic effect. We recently developed a dual-GDEPT system where we combined mutant human herpes simplex thymidine kinase (HSV1sr39TK) and E. coli nitroreductase (NTR) enzyme, to improve therapeutic efficiency of cancer gene therapy by simultaneously injecting two prodrugs at a lower dose. In this approach we use two different prodrugs such as ganciclovir (GCV) and CB1954 to target two different cellular mechanisms to kill cancer cells. The developed dual GDEPT system was highly efficacious than that of either of the system used independently. In this chapter, we describe the complete protocol involved for in vitro and in vivo imaging of therapeutic cancer gene therapy evaluation.

Gene and cell therapy for pancreatic cancer.

PubMed

Singh, Hans Martin; Ungerechts, Guy; Tsimberidou, Apostolia M

2015-04-01

The clinical outcomes of patients with pancreatic cancer are poor, and the limited success of classical chemotherapy underscores the need for new, targeted approaches for this disease. The delivery of genetic material to cells allows for a variety of therapeutic concepts. Engineered agents based on synthetic biology are under clinical investigation in various cancers, including pancreatic cancer. This review focuses on Phase I - III clinical trials of gene and cell therapy for pancreatic cancer and on future implications of recent translational research. Trials available in the US National Library of Medicine (www.clinicaltrials.gov) until February 2014 were reviewed and relevant published results of preclinical and clinical studies were retrieved from www.pubmed.gov . In pancreatic cancer, gene and cell therapies are feasible and may have synergistic antitumor activity with standard treatment and/or immunotherapy. Challenges are related to application safety, manufacturing costs, and a new spectrum of adverse events. Further studies are needed to evaluate available agents in carefully designed protocols and combination regimens. Enabling personalized cancer therapy, insights from molecular diagnostic technologies will guide the development and selection of new gene-based drugs. The evolving preclinical and clinical data on gene-based therapies can lay the foundation for future avenues improving patient care in pancreatic cancer.

Technology improves upper extremity rehabilitation.

PubMed

Kowalczewski, Jan; Prochazka, Arthur

2011-01-01

Stroke survivors with hemiparesis and spinal cord injury (SCI) survivors with tetraplegia find it difficult or impossible to perform many activities of daily life. There is growing evidence that intensive exercise therapy, especially when supplemented with functional electrical stimulation (FES), can improve upper extremity function, but delivering the treatment can be costly, particularly after recipients leave rehabilitation facilities. Recently, there has been a growing level of interest among researchers and healthcare policymakers to deliver upper extremity treatments to people in their homes using in-home teletherapy (IHT). The few studies that have been carried out so far have encountered a variety of logistical and technical problems, not least the difficulty of conducting properly controlled and blinded protocols that satisfy the requirements of high-level evidence-based research. In most cases, the equipment and communications technology were not designed for individuals with upper extremity disability. It is clear that exercise therapy combined with interventions such as FES, supervised over the Internet, will soon be adopted worldwide in one form or another. Therefore it is timely that researchers, clinicians, and healthcare planners interested in assessing IHT be aware of the pros and cons of the new technology and the factors involved in designing appropriate studies of it. It is crucial to understand the technical barriers, the role of telesupervisors, the motor improvements that participants can reasonably expect and the process of optimizing IHT-exercise therapy protocols to maximize the benefits of the emerging technology. Copyright © 2011 Elsevier B.V. All rights reserved.

Early childhood constraint therapy for sensory/motor impairment in cerebral palsy: a randomised clinical trial protocol

PubMed Central

Chorna, Olena; Heathcock, Jill; Key, Alexandra; Noritz, Garey; Carey, Helen; Hamm, Ellyn; Nelin, Mary Ann; Murray, Micah; Needham, Amy; Slaughter, James C; Maitre, Nathalie L

2015-01-01

Introduction Cerebral palsy (CP) is the most common physical disability in childhood. It is a disorder resulting from sensory and motor impairments due to perinatal brain injury, with lifetime consequences that range from poor adaptive and social function to communication and emotional disturbances. Infants with CP have a fundamental disadvantage in recovering motor function: they do not receive accurate sensory feedback from their movements, leading to developmental disregard. Constraint-induced movement therapy (CIMT) is one of the few effective neurorehabilitative strategies shown to improve upper extremity motor function in adults and older children with CP, potentially overcoming developmental disregard. Methods and analysis This study is a randomised controlled trial of children 12–24 months corrected age studying the effectiveness of CIMT combined with motor and sensory-motor interventions. The study population will comprise 72 children with CP and 144 typically developing children for a total of N=216 children. All children with CP, regardless of group allocation will continue with their standard of care occupational and physical therapy throughout the study. The research material collected will be in the form of data from high-density array event-related potential scan, standardised assessment scores and motion analysis scores. Ethics and dissemination The study protocol was approved by the Institutional Review Board. The findings of the trial will be disseminated through peer-reviewed journals and scientific conferences. Trial registration number NCT02567630. PMID:26644127

Effects of a single-session assertiveness music therapy role playing protocol for psychiatric inpatients.

PubMed

Silverman, Michael J

2011-01-01

The purpose of this study was to implement and measure the effectiveness of a single-session assertiveness music therapy role playing protocol for psychiatric inpatients. Participants (N=133) were randomly assigned by group to one of three conditions: (a) Assertiveness Music Therapy, (b) No Music Assertiveness, or (c) Music No Assertiveness. Participants in both assertiveness conditions role played a number of different commonly occurring scenarios at an inpatient psychiatric facility and in the community. There were no significant between-group differences in posttest quality of life, locus of control, or other subscales. However, participants in both assertiveness conditions tended to have slightly higher internal locus of control and overall quality of life scores than participants in the music no assertiveness condition. Additionally, the assertiveness music therapy condition had higher attendance rates than the other conditions. A higher percentage of participants from both the assertiveness music therapy and music no assertiveness conditions indicated they thought their session was the most helpful/therapeutic group therapy session in which they had participated; this was not the case for the assertiveness no music condition. Future research is warranted to measure the effects of protocols that can help psychiatric patients generalize skills learned in treatment.

Propionibacterium acnes Augments Antitumor, Anti-Angiogenesis and Immunomodulatory Effects of Melatonin on Breast Cancer Implanted in Mice

PubMed Central

Talib, Wamidh H.; Saleh, Suhair

2015-01-01

Breast cancer is one of the most invasive cancers with high mortality. The immune stimulating Propionibacterium acnes is a Gram positive bacterium that has the ability to cause inflammation and activate Th1-type cytokine immune response. Antitumor response was associated with the inflammation induced by P. acnes, but the antitumor effect of this bacterium was not evaluated in combination with other agents. The aim of this study was to test the antitumor potential of a combination of melatonin and P. acnes against breast cancer implanted in mice. Balb/C mice were transplanted with EMT6/P cell line and in vivo antitumor effect was assessed for P. acnes, melatonin, and a combination of melatonin and P. acnes. Tumor and organs sections were examined using hematoxylin/eosin staining protocol, and TUNEL colorimetric assay was used to detect apoptosis. The expression of vascular endothelial growth factor (VEGF) was measured in tumor sections and serum levels of INF-γ, and IL-4 were measured to evaluate the immune system function. To evaluate the toxicity of our combination, AST and ALT levels were measured in the serum of treated mice. The combination of melatonin and P. acnes has high efficiency in targeting breast cancer in mice. Forty percent of treated mice were completely cured using this combination and the combination inhibited metastasis of cancer cells to other organs. The combination therapy reduced angiogenesis, exhibited no toxicity, induced apoptosis, and stimulates strong Th1-type cytokine antitumor immune response. The combination of melatonin and P. acnes represents a promising option to treat breast cancer. However, carful preclinical and clinical evaluation is needed before considering this combination for human therapy. PMID:25919398

Evolving paradigms for desensitization in managing broadly HLA sensitized transplant candidates.

PubMed

Reinsmoen, Nancy L; Lai, Chi-Hung; Vo, Ashley; Jordan, Stanley C

2012-04-01

The broadly human leukocyte antigen (HLA) sensitized patient awaiting organ transplantation remains a persistent and significant problem for transplant medicine. Sensitization occurs as a consequence of exposure to HLA antigens through pregnancy, blood and platelet transfusions, and previous transplants. Early experience with desensitization protocols coupled with improved diagnostics for donor-specific antibodies (DSAs) and renal pathology have greatly improved transplant rates and outcomes for patients once considered un-transplantable or at high risk for poor outcomes. More recent advances have occurred through implementation of a national allocation system requiring the entering of unacceptable antigens that reduces the rate of crossmatch positivity. Current desensitization therapies include high-dose intravenous immunoglobulin (IVIG), plasma exchange (PLEX) with low-dose IVIG, and IVIG combined with rituximab. Developing therapies include proteasome inhibitors aimed at plasma cells and modifiers of complement-mediated injury. Here we discuss the important advancements in desensitization including defining the risk for antibody-mediated rejection prior to transplantation and the evolution of therapies aimed at reducing the impact of antibody injury on allografts.

Intraoperative radiotherapy. Literature updating with an overview of results presented at the 6th International Symposium of Intraoperative Radiation Therapy.

PubMed

Calvo, F A; Santos, M; Azinovic, I

1998-01-01

Intraoperative radiotherapy is a technique that can be integrated into multidisciplinary treatment strategies in oncology. A radiation boost delivered with high energy electron beams can intensify locoregional antitumor therapy in patients undergoing cancer surgery. Intraoperative radiotherapy can increase the therapeutic index of the conventional combination of surgery and radiotherapy by improving the precision of radiation dose location, while decreasing the normal tissue damage in mobile structures and enhancing the biological effect of radiation when combined with surgical debulking. Intraoperative radiotherapy has been extensively investigated in clinical oncology in the last 15 years. Commercially available linear accelerators require minimal changes to be suitable for intraoperative radiotherapy. Its successful implementation in clinical protocols depends on the support given by the single institutions and on a clinical research-oriented mentality. Tumors where intraoperative radiotherapy as a treatment component has shown promising rates of local control include locally advanced rectal, gastric and gynecologic cancer, bone and soft tissue sarcoma. Intraoperative radiotherapy can be applied to brain tumors, head and neck cancer, NSCLC and pancreatic carcinoma.

Effectiveness of neurofeedback therapy for anxiety and stress in adults living with a chronic illness: a systematic review protocol.

PubMed

Blaskovits, Farriss; Tyerman, Jane; Luctkar-Flude, Marian

2017-07-01

The objective of this review is to systematically examine the effectiveness of neurofeedback therapy for managing anxiety and stress in adults living with a chronic illness.The specific objectives are to identify which neurofeedback systems and/or protocols demonstrate effectiveness and determine the level of supporting evidence.The review question is as follows: What is the effectiveness of neurofeedback therapy for managing anxiety and stress in an adult population aged 18 years of age or older living with a chronic illness?

Practice, progress and future directions for physical therapies in Huntingtons disease.

PubMed

Busse, Monica; Khalil, Hanan; Brooks, Simon; Quinn, Lori; Rosser, Anne

2012-01-01

Physical therapies and exercise may have potential as a disease modifying agent in Huntington's disease (HD) and in recent years, there have been several small scale feasibility studies that have shown benefit as a result of physical interventions. When evaluating complex physical interventions, a phased approach using mixed methodology designs that report specific intervention components, adherence, acceptability, adverse events and defined intervention protocols is important for replication and planning of future trials and to ensure potential for implementation in clinical practice. A narrative review of the available literature related to physical activity, physical therapy and exercise in people with HD was performed using a population, intervention, comparison and outcome (PICO) approach. Eight studies met specific inclusion criteria and were reviewed in terms of their systematic conduct and reporting standards. All of the studies (n = 8) provided details of intervention including location and duration. The majority of interventions included balance training activities in combination with other complex activities of daily living that required therapist supervision. Two of the interventions were home based, the remainder were facility or hospital based. None of the studies reported adverse events whilst only 3/8 reported adherence rates which were ranging from 60-80%. In general, limited detail was provided on the specific individual components of the interventions. This review of primary publications and conference proceedings, suggests that researchers working in the field need to focus on clearer reporting of intervention protocols so as to generate a clearer understanding of the impact of exercise and physical therapies on the symptoms of HD, as well as any potential synergistic role alongside the impending disease-modifying interventions.

Induction with Infliximab and a Plant-Based Diet as First-Line (IPF) Therapy for Crohn Disease: A Single-Group Trial

PubMed Central

Chiba, Mitsuro; Tsuji, Tsuyotoshi; Nakane, Kunio; Tsuda, Satoko; Ishii, Hajime; Ohno, Hideo; Watanabe, Kenta; Ito, Mai; Komatsu, Masafumi; Sugawara, Takeshi

2017-01-01

Background Approximately 30% of patients with Crohn disease (CD) are unresponsive to biologics. No previous study has focused on a plant-based diet in an induction phase of CD treatment. Objective To investigate the remission rate of infliximab combined with a plant-based diet as first-line (IPF) therapy for CD. Methods This was a prospective single-group trial conducted at tertiary hospitals. Subjects included consecutive adults with a new diagnosis (n = 26), children with a new diagnosis (n = 11), and relapsing adults (n = 9) with CD who were naïve to treatment with biologics. Patients were admitted and administered a standard induction therapy with infliximab (5 mg/kg; 3 infusions at 0, 2, and 6 weeks). Additionally, they received a lacto-ovo-semivegetarian diet. The primary end point was remission, defined as the disappearance of active CD symptoms at week 6. Secondary end points were Crohn Disease Activity Index (CDAI) score, C-reactive protein (CRP) concentration, and mucosal healing. Results Two adults with a new diagnosis were withdrawn from the treatment protocol because of intestinal obstruction. The remission rates by the intention-to-treat and per-protocol analyses were 96% (44/46) and 100% (44/44), respectively. Mean CDAI score (314) on admission decreased to 63 at week 6 (p < 0.0001). Mean CRP level on admission (5.3 mg/dL) decreased to 0.2 (p < 0.0001). Mucosal healing was achieved in 46% (19/41) of cases. Conclusion IPF therapy can induce remission in most patients with CD who are naïve to biologics regardless of age or whether they have a new diagnosis or relapse. PMID:29035182

Bundled Postconditioning Therapies Improve Hemodynamics and Neurologic Recovery after 17 Minutes of Untreated Cardiac Arrest

PubMed Central

Bartos, Jason A.; Matsuura, Timothy R.; Sarraf, Mohammad; Youngquist, Scott T.; McKnite, Scott H.; Rees, Jennifer N.; Sloper, Daniel T.; Bates, Frank S.; Segal, Nicolas; Debaty, Guillaume; Lurie, Keith G.; Neumar, Robert W.; Metzger, Joseph M.; Riess, Matthias L.; Yannopoulos, Demetris

2014-01-01

Objective Ischemic postconditioning (stutter CPR) and sevoflurane have been shown to mitigate the effects of reperfusion injury in cardiac tissue after 15 minutes of ventricular fibrillation (VF) cardiac arrest. Poloxamer 188 (P188) has also proven beneficial to neuronal and cardiac tissue during reperfusion injury in human and animal models. We hypothesized that the use of stutter CPR, sevoflurane, and P188 combined with standard advanced life support would improve post-resuscitation cardiac and neurologic function after prolonged VF arrest. Methods Following 17 minutes of untreated VF, 20 pigs were randomized to Control treatment with active compression/decompression (ACD) CPR and impedance threshold device (ITD) (n=8) or Bundle therapy with stutter ACD CPR + ITD + sevoflurane + P188 (n=12). Epinephrine and post-resuscitation hypothermia were given in both groups per standard protocol. Animals that achieved return of spontaneous circulation (ROSC) were evaluated with echocardiography, biomarkers, and a blinded neurologic assessment with a cerebral performance category score. Results Bundle therapy improved hemodynamics during resuscitation, reduced need for epinephrine and repeated defibrillation, reduced biomarkers of cardiac injury and end-organ dysfunction, and increased left ventricular ejection fraction compared to Controls. Bundle therapy also improved rates of ROSC (100% vs. 50%), freedom from major adverse events (50% vs. 0% at 48 hours), and neurologic function (42% with mild or no neurologic deficit and 17% achieving normal function at 48 hours). Conclusions Bundle therapy with a combination of stutter ACD CPR, ITD, sevoflurane, and P188 improved cardiac and neurologic function after 17 minutes of untreated cardiac arrest in pigs. PMID:25447036

Comparison of alternative βhCG follow-up protocols after single-dose methotrexate therapy for tubal ectopic pregnancy.

PubMed

Şükür, Yavuz Emre; Koyuncu, Kazibe; Seval, Mehmet Murat; Çetinkaya, Esra; Dökmeci, Fulya

2017-12-01

To evaluate the performances of five different βhCG follow-up protocols after single-dose methotrexate therapy for tubal ectopic pregnancy (EP). Data of patients who received single-dose methotrexate therapy for tubal EP at a university hospital between January 2011 and July 2016 were reviewed. A 'successful methotrexate treatment' was defined if the EP treated with no need for surgery. The performances of different protocols were tested by comparing with the currently used '15% βhCG decrease between days 4 and 7' protocol. The tested follow-up protocols were '20, 25%, and any βhCG decrease between days 0/1 and 7' and '20% and any βhCG decrease between days 0/1 and 4'. Among the 96 patients evaluated, 12 (12.5%) required second dose. Totally, 91 (94.8%) patients treated successfully with no need for surgery. Four patients were operated within 4 days following the second dose. One patient who did not need second dose according to the standard follow-up protocol was operated on the 10th day due to rupture (specificity = 80%). Two protocols, namely '20% βhCG decrease between days 0/1 and 7' and 'any βhCG decrease between days 0/1 and 7' did not show statistically significant differences from the index protocol regarding the number of patients who should be assigned to 2nd dose. 'Any βhCG decrease between days 0/1 and 7' protocol may substitute the currently used one to decide second dose methotrexate in tubal EP management. Omitting 4th day measurement seems to be more convenient and cost effective.

Identification of combinatorial drug regimens for treatment of Huntington's disease using Drosophila

NASA Astrophysics Data System (ADS)

Agrawal, Namita; Pallos, Judit; Slepko, Natalia; Apostol, Barbara L.; Bodai, Laszlo; Chang, Ling-Wen; Chiang, Ann-Shyn; Michels Thompson, Leslie; Marsh, J. Lawrence

2005-03-01

We explore the hypothesis that pathology of Huntington's disease involves multiple cellular mechanisms whose contributions to disease are incrementally additive or synergistic. We provide evidence that the photoreceptor neuron degeneration seen in flies expressing mutant human huntingtin correlates with widespread degenerative events in the Drosophila CNS. We use a Drosophila Huntington's disease model to establish dose regimens and protocols to assess the effectiveness of drug combinations used at low threshold concentrations. These proof of principle studies identify at least two potential combinatorial treatment options and illustrate a rapid and cost-effective paradigm for testing and optimizing combinatorial drug therapies while reducing side effects for patients with neurodegenerative disease. The potential for using prescreening in Drosophila to inform combinatorial therapies that are most likely to be effective for testing in mammals is discussed. combinatorial treatments | neurodegeneration

[Pilot study of antiretroviral therapy in Djibouti].

PubMed

Ahmed, A A; Latoundji, S

2007-01-01

A cross-sectional survey was conducted among 112 HIV positive patients who had received antiretroviral therapy for >3 months to assess the efficacy of treatment (viral load <400 copies/mL). The median age at enrolment was 36 years, 90% of patients were at the AIDS stage and median CD4 rate was 118/mm3. Patients received a combined treatment of 2 NRTI +1 NNRTI (51%), 3 NRTI (45%) and 2 NRTI+1 PI (4%). Virological efficacy was seen in 74% of the patients, irrespective of the prescribed protocol and the initial clinical and immunological profile. Mean improvements measured were 20% on the Karnofsky index (KI), 2.1 kg/m2 in body mass index and 82 cells/mm in CD4. The prevalence of side effects was 84%. The predictors for treatment success were quality of care and KI > 70%.

Photodynamic therapy in endodontics: a literature review.

PubMed

Trindade, Alessandra Cesar; De Figueiredo, José Antônio Poli; Steier, Liviu; Weber, João Batista Blessmann

2015-03-01

Recently, several in vitro and in vivo studies demonstrated promising results about the use of photodynamic therapy during root canal system disinfection. However, there is no consensus on a standard protocol for its incorporation during root canal treatment. The purpose of this study was to summarize the results of research on photodynamic therapy in endodontics published in peer-reviewed journals. A review of pertinent literature was conducted using the PubMed database, and data obtained were categorized into sections in terms of relevant topics. Studies conducted in recent years highlighted the antimicrobial potential of photodynamic therapy in endodontics. However, most of these studies were not able to confirm a significant improvement in root canal disinfection for photodynamic therapy as a substitute for current disinfection methods. Its indication as an excellent adjunct to conventional endodontic therapy is well documented, however. Data suggest the need for protocol adjustments or new photosensitizer formulations to enhance photodynamic therapy predictability in endodontics.

Does Music Therapy Improve Anxiety and Depression in Alzheimer's Patients?

PubMed

de la Rubia Ortí, José Enrique; García-Pardo, María Pilar; Iranzo, Carmen Cabañés; Madrigal, José Joaquin Cerón; Castillo, Sandra Sancho; Rochina, Mariano Julián; Gascó, Vicente Javier Prado

2018-01-01

To evaluate the effectiveness of the implementation of a short protocol of music therapy as a tool to reduce stress and improve the emotional state in patients with mild Alzheimer's disease. A sample of 25 patients with mild Alzheimer's received therapy based on the application of a music therapy session lasting 60 min. Before and after the therapy, patient saliva was collected to quantify the level of salivary cortisol using the Enzyme-Linked ImmunoSorbent Assay (ELISA) immunoassay technique and a questionnaire was completed to measure anxiety and depression (Hospital Anxiety and Depression Scale). The results show that the application of this therapy lowers the level of stress and decreases significantly depression and anxiety, establishing a linear correlation between the variation of these variables and the variation of cortisol. A short protocol of music therapy can be an alternative medicine to improve emotional variables in Alzheimer patients.

Protocolized fluid therapy in brain-dead donors: the multicenter randomized MOnIToR trial.

PubMed

Al-Khafaji, Ali; Elder, Michele; Lebovitz, Daniel J; Murugan, Raghavan; Souter, Michael; Stuart, Susan; Wahed, Abdus S; Keebler, Ben; Dils, Dorrie; Mitchell, Stephanie; Shutterly, Kurt; Wilkerson, Dawn; Pearse, Rupert; Kellum, John A

2015-03-01

Critical shortages of organs for transplantation jeopardize many lives. Observational data suggest that better fluid management for deceased organ donors could increase organ recovery. We conducted the first large multicenter randomized trial in brain-dead donors to determine whether protocolized fluid therapy increases the number of organs transplanted. We randomly assigned donors to either protocolized or usual care in eight organ procurement organizations. A "protocol-guided fluid therapy" algorithm targeting the cardiac index, mean arterial pressure and pulse pressure variation was used. Our primary outcome was the number of organs transplanted per donor, and our primary analysis was intention to treat. Secondary analyses included: (1) modified intention to treat where only subjects able to receive the intervention were included and (2) 12-month survival in transplant recipients. The study was stopped early. We enrolled 556 donors: 279 protocolized care and 277 usual care. Groups had similar characteristics at baseline. The study protocol could be implemented in 76 % of subjects randomized to the intervention. There was no significant difference in mean number of organs transplanted per donor: 3.39 organs per donor (95 % CI 3.14-3.63) with protocolized care compared to 3.29 usual care (95 % CI 3.04-3.54; mean difference, 0.1, 95 % CI -0.25 to 0.45; p = 0.56). In modified intention-to-treat analysis the mean number of organs increased (3.52 organs per donor, 95 % CI 3.23-3.8), but not statistically significantly (mean difference, 0.23, 95 % CI -0.15 to 0.61; p = 0.23). Among the 1,430 recipients of organs from study subjects with data available, 56 deaths (7.8 %) occurred in the protocolized care arm and 56 (7.9 %) in the usual care arm in the first year (hazard ratio: 0.97, p = 0.86). In brain-dead organ donors, protocol-guided fluid therapy compared to usual care may not increase the number of organs transplanted per donor.

Efficacy of protocol-based pharmacotherapy management on anticoagulation with warfarin for patients with cardiovascular surgery.

PubMed

Katada, Y; Nakagawa, S; Minakata, K; Odaka, M; Taue, H; Sato, Y; Yonezawa, A; Kayano, Y; Yano, I; Nakatsu, T; Sakamoto, K; Uehara, K; Sakaguchi, H; Yamazaki, K; Minatoya, K; Sakata, R; Matsubara, K

2017-10-01

Anticoagulation therapy with warfarin requires periodic monitoring of prothrombin time-international normalized ratio (PT-INR) and adequate dose adjustments based on the data to minimize the risk of bleeding and thromboembolic events. In our hospital, we have developed protocol-based pharmaceutical care, which we called protocol-based pharmacotherapy management (PBPM), for warfarin therapy. The protocol requires pharmacists to manage timing of blood sampling for measuring PT-INR and warfarin dosage determination based on an algorithm. This study evaluated the efficacy of PBPM in warfarin therapy by comparing to conventional pharmaceutical care. From October 2013 to June 2015, a total of 134 hospitalized patients who underwent cardiovascular surgeries received post-operative warfarin therapy. The early series of patients received warfarin therapy as the conventional care (control group, n=77), whereas the latter received warfarin therapy based on the PBPM (PBPM group, n=68). These patients formed the cohort of the present study and were retrospectively analysed. The indications for warfarin included aortic valve replacement (n=56), mitral valve replacement (n=4), mitral valve plasty (n=22) and atrial fibrillation (n=29). There were no differences in patients' characteristics between both groups. The percentage time in therapeutic range in the first 10 days was significantly higher in the PBPM group (47.1%) than that in the control group (34.4%, P<.005). The average time to reach the steady state was significantly (P<.005) shorter in the PBPM group compared to the control group (7.3 vs 8.6 days). Warfarin therapy based on our novel PBPM was clinically safe and resulted in significantly better anticoagulation control compared to conventional care. © 2017 John Wiley & Sons Ltd.

The utilization of unified protocols in behavioral cognitive therapy in transdiagnostic group subjects: A clinical trial.

PubMed

de Ornelas Maia, Ana Claudia Corrêa; Nardi, Antonio Egidio; Cardoso, Adriana

2015-02-01

The practicing of protocols based on behavioral cognitive therapy (CBT) have been frequently used in the last decades and adapted to better manage the necessities of patients and providers. The goal is to build a treatment that is evidence-based - for that reason the unified protocol for multiple emotional disorders (transdiagnostics) have been utilized to simplify treatment - without losing scientific traits. The main goal of this study is to evaluate the unified protocol in groups of patients with depression and anxiety disorders. In a pool of 48 subjects, divided in two groups, one was submitted to 12 intervention sessions of the unified protocol while the other was solely given medication. MINI, BAI and BDI were the instruments used at the beginning and at the end of treatment. The results were highly significant (p<0.001) in as much as with the improvement of anxiety and depressive disorders as it was in the group which was treated with the unified protocol compared with the group which was only given medication Limitations of this study were the number of sample participants and the non-randomization of subjects in both groups. Group therapy has not been largely implemented though it is deemed very useful for treatments when the unified protocol is used in transdiagnostic patients. Not only does it allow for emotional stabilizing and socialization but it also enables subjects with an altruistic feeling amongst themselves. Copyright © 2014 Elsevier B.V. All rights reserved.

SU-E-T-581: Planning Evaluation of Step-And-Shoot IMRT, RapidArc and Helical TomoTherapy for Hippocampal-Avoidance Whole Brain Radiotherapy (HA-WBRT).

PubMed

Evans, J; Chen, Q; Wuthrick, E; Weldon, M; Rong, Y

2012-06-01

Several planning strategies are available for hippocampal- avoidance whole-brain radiotherapy (HA-WBRT) following RTOG protocol 0933, but have yet to be compared on a common set of patient data. In this inter-institutional investigation, we evaluate three modalities likely to be employed by protocol participants; step-and-shoot IMRT, volumetric modulated arc therapy, and helical tomotherapy. A common set of patients is used for comparison, including credentialing and successfully accrued patients. Eight patient datasets were selected and de-identified prior to planning. Structures were contoured by physicians per protocol using fused MRI datasets. Three plans were generated for each dataset: Philips Pinnacle 9-field non-coplanar IMRT using protocol recommended beam parameters, Varian's RapidArc using two coplanar arcs, and Accuray's TomoTherapy using a 1cm jaw width. With the goal of meeting the compliance criteria outlined in RTOG 0933 (target coverage and dose limits to the hippocampus and optic structures), three planners independently planned each modality without prior knowledge of the patient's other plans to reduce bias. The three plans for each patient were compared according to the protocol's dosimetric compliance criteria. A homogeneity index was also computed to compare target dose uniformity. All plans achieved the protocol dose criteria, except for one RapidArc plan with slightly inferior dose to the optic chiasm. TomoTherapy offered superior dose homogeneity for all patients. For the two linac based methods, RapidArc was found to provide dose homogeneity at least as good as, and in most cases superior to, 9-field step-and-shoot IMRT. Helical TomoTherapy offers superior dose homogeneity for HA-WBRT following RTOG 0933. Compared to step-and-shoot IMRT, volumetric modulated arc techniques, such as RapidArc, can offer improved homogeneity for HA- WBRT and are generally more efficient/expeditious to deliver than the noncoplanar 9-field arrangement recommended by the protocol, which uses 7 separate couch angles. © 2012 American Association of Physicists in Medicine.

[Acceptance and commitment therapy (ACT) and improving chess performance in promising young chess-players].

PubMed

Ruiz, Francisco J; Luciano, Carmen

2009-08-01

Acceptance and Commitment Therapy (ACT) is shown to be effective in relatively distant fields from the so-called psychological disorders. One of these areas is sport performance improvement. The aim of the current study is to expand the application of brief ACT protocols to improve chess-players' performance. In a previous study, a brief protocol was applied to international-level adult chess-players that was effective. The current study aims to apply an equivalent brief ACT protocol, but in this case, applied in a group format to promising young chess-players. In addition, this brief protocol is compared to a non-intervention control condition. Results show that the ACT brief protocol improved the performance in 5 out of 7 participants, and that none of the chess-players in the control condition reached the established change criterion. The differences between the conditions in chess performance were statistically significant. The results are discussed, emphasizing the replicated impact of a brief ACT protocol on the improvement of chess-players' performance.

Phase I study of combined therapy with vorinostat and gefitinib to treat BIM deletion polymorphism-associated resistance in EGFR-mutant lung cancer (VICTROY-J): a study protocol.

PubMed

Takeuchi, Shinji; Yoshimura, Kenichi; Fujiwara, Tadami; Ando, Masahiko; Shimizu, Shinobu; Nagase, Katsuhiko; Hasegawa, Yoshinori; Takahashi, Toshiaki; Katakami, Nobuyuki; Inoue, Akira; Yano, Seiji

2017-01-01

The BIM deletion polymorphism is reported to be associated with poor outcomes of epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) treated with EGFR-TKIs, including gefitinib. We have shown that a histone deacetylase inhibitor, vorinostat, can epigenetically restore BIM function and apoptosis sensitivity to EGFR-TKIs in EGFR-mutant NSCLC cells with BIM deletion polymorphisms. The purpose of this study is to determine the feasibility of combined treatment of vorinostat with gefitinib in BIM deletion polymorphism positive EGFR-mutant NSCLC patients. BIM deletion polymorphism positive EGFR-mutant NSCLC patients treated with at least one EGFR-TKI and one regimen of chemotherapy are being recruited to this study. Vorinostat (200-400 mg) will be administered orally once daily on days 1-7, and gefitinib 250 mg orally once daily on days 1-14. With a fixed dose of gefitinib, the dose of vorinostat will be escalated following a conventional 3+3 design. The primary endpoint is to define the maximum tolerated dose (MTD) of vorinostat combined with 250 mg of gefitinib. This is the first phase I study of combined therapy with vorinostat and gefitinib for NSCLC patients double selected for an EGFR mutation and BIM deletion polymorphism. J. Med. Invest. 64: 321-325, August, 2017.

ITALIAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS STATEMENT-REPLACEMENT THERAPY FOR PRIMARY HYPOTHYROIDISM: A BRIEF GUIDE FOR CLINICAL PRACTICE.

PubMed

Guglielmi, Rinaldo; Frasoldati, Andrea; Zini, Michele; Grimaldi, Franco; Gharib, Hossein; Garber, Jeffrey R; Papini, Enrico

2016-11-01

Hypothyroidism requires life-long thyroid hormone replacement therapy in most patients. Oral levothyroxine (LT4) is an established safe and effective treatment for hypothyroidism, but some issues remain unsettled. The Italian Association of Clinical Endocrinologists appointed a panel of experts to provide an updated statement for appropriate use of thyroid hormone formulations for hypothyroidism replacement therapy. The American Association of Clinical Endocrinologists' protocol for standardized production of clinical practice guidelines was followed. LT4 is the first choice in replacement therapy. Thyroid-stimulating hormone (TSH) should be maintained between 1.0 and 3.0 mIU/L in young subjects and at the upper normal limit in elderly or fragile patients. Achievement of biochemical targets, patient well-being, and adherence to treatment should be addressed. In patients with unstable serum TSH, a search for interfering factors and patient compliance is warranted. Liquid or gel formulations may be considered in subjects with hampered LT4 absorption or who do not allow sufficient time before or after meals and LT4 replacement. Replacement therapy with LT4 and L-triiodothyronine (LT3) combination is generally not recommended. A trial may be considered in patients with normal values of serum TSH who continue to complain of symptoms of hypothyroidism only after co-existent nonthyroid problems have been excluded or optimally managed. LT3 should be administered in small (LT4:LT3 ratio, 10:1 to 20:1) divided daily doses. Combined therapy should be avoided in elderly patients or those with cardiac risk factors and in pregnancy. LT4 therapy should be aimed at resolution of symptoms of hypothyroidism, normalization of serum TSH, and improvement of quality of life. In selected cases, the use of liquid LT4 formulations or combined LT4/LT3 treatment may be considered to improve adherence to treatment or patient well-being. AACE = American Association of Clinical Endocrinologists FT3 = free triiodothyronine FT4 = free thyroxine LT3 = levotriiodothyronine LT4 = levothyroxine MeSH = medicine medical subject headings QoL = quality of life TSH = thyroid-stimulating hormone.

Economic comparison of common treatment protocols and J5 vaccination for clinical mastitis in dairy herds using optimized culling decisions.

PubMed

Kessels, J A; Cha, E; Johnson, S K; Welcome, F L; Kristensen, A R; Gröhn, Y T

2016-05-01

This study used an existing dynamic optimization model to compare costs of common treatment protocols and J5 vaccination for clinical mastitis in US dairy herds. Clinical mastitis is an infection of the mammary gland causing major economic losses in dairy herds due to reduced milk production, reduced conception, and increased risk of mortality and culling for infected cows. Treatment protocols were developed to reflect common practices in dairy herds. These included targeted therapy following pathogen identification, and therapy without pathogen identification using a broad-spectrum antimicrobial or treating with the cheapest treatment option. The cost-benefit of J5 vaccination was also estimated. Effects of treatment were accounted for as changes in treatment costs, milk loss due to mastitis, milk discarded due to treatment, and mortality. Following ineffective treatments, secondary decisions included extending the current treatment, alternative treatment, discontinuing treatment, and pathogen identification followed by recommended treatment. Average net returns for treatment protocols and vaccination were generated using an existing dynamic programming model. This model incorporates cow and pathogen characteristics to optimize management decisions to treat, inseminate, or cull cows. Of the treatment protocols where 100% of cows received recommended treatment, pathogen-specific identification followed by recommended therapy yielded the highest average net returns per cow per year. Out of all treatment scenarios, the highest net returns were achieved with selecting the cheapest treatment option and discontinuing treatment, or alternate treatment with a similar spectrum therapy; however, this may not account for the full consequences of giving nonrecommended therapies to cows with clinical mastitis. Vaccination increased average net returns in all scenarios. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Pregabalin as mono- or add-on therapy for patients with refractory chronic neuropathic pain: a post-marketing prescription-event monitoring study.

PubMed

Lampl, Christian; Schweiger, Christine; Haider, Bernhard; Lechner, Anita

2010-08-01

This observational study examined the outcome of two different therapeutic strategies in the treatment of chronic neuropathic pain by including pregabalin (PGB) as mono- or add-on therapy in one of two treatment options. Patients with a pain score of > or =4, refractory to usual care for neuropathic pain for at least 6 months, were allocated consecutively to one of two treatment strategies according to the decision of the physician: complete switch to a flexible-dosage, monotherapeutic or add-on therapy with pregabalin (PGB group), or change established doses and combinations of pre-existing mono- or combination therapy without pregabalin (non-PGB group). After 4 weeks (primary endpoint) a significant improvement in pain reduction was documented in both intention-to treat (ITT) analysis (PGB group, n = 85: mean pain score reduction of 3.53, SD 2.03, p < 0.001; non-PGB group, n = 102; mean pain score reduction of 2.83, SD 2.23, p < 0.001) and per-protocol (PP) analysis (PGB group, n = 79: mean pain score reduction 3.53 vs. 2.83, p < 0.05; non-PGB group, n = 81; 3.5 vs. 2.9, p < 0.05) compared to baseline. Comparison of the results observed in the two groups shows that patients in the PGB group achieved significantly greater pain reduction. These results demonstrate that PGB administered twice daily is superior to treatment regimes without PGB in reducing pain and pain-related interference in quality of life.

Effect of zoledronic acid and amputation on bone invasion and lung metastasis of canine osteosarcoma in nude mice

PubMed Central

Wolfe, Tobie D.; Somanathan Pillai, Smitha Pankajavally; Hildreth, Blake Eason; Lanigan, Lisa G.; Martin, Chelsea K.; Werbeck, Jillian L.

2014-01-01

Osteosarcoma (OSA) is an aggressive, highly metastatic and lytic primary bone neoplasm commonly affecting the appendicular skeleton of dogs and children. Current treatment options include amputation of the afflicted limb, limb-sparing procedures, or palliative radiation with or without adjunct chemotherapy. Therapies that inhibit bone resorption, such as the bisphosphonates, may be an effective palliative therapy by limiting the local progression of OSA in those patients that are not viable candidates for amputation. We have developed a mouse model of canine skeletal OSA following intratibial inoculation of OSCA40 cells that spontaneously metastasized to the lungs. We demonstrated that therapy with a nitrogen-containing bisphosphonate, zoledronic acid (Zol), reduced OSA-induced bone lysis; however, Zol monotherapy or in combination with amputation was not effective at inhibiting pulmonary metastasis. While not reaching statistical significance, amputation of the tumor-bearing limb reduced the average incidence of lung metastases; however, this effect was nullified when Zol was added to the treatment protocol. In untreated mice, the magnitude of proximal tibial lysis was significantly correlated with the incidence of metastasis. The data support amputation alone for the management of appendicular OSA rather than combining amputation with Zol. However, in patients that are not viable candidates for amputation, Zol may be a useful palliative therapy for OSA by reducing the magnitude of lysis and therefore bone pain, despite the risk of increased pulmonary metastasis. PMID:21374084

Merging Theoretical Models and Therapy Approaches in the Context of Internet Gaming Disorder: A Personal Perspective.

PubMed

Young, Kimberly S; Brand, Matthias

2017-01-01

Although, it is not yet officially recognized as a clinical entity which is diagnosable, Internet Gaming Disorder (IGD) has been included in section III for further study in the DSM-5 by the American Psychiatric Association (APA, 2013). This is important because there is increasing evidence that people of all ages, in particular teens and young adults, are facing very real and sometimes very severe consequences in daily life resulting from an addictive use of online games. This article summarizes general aspects of IGD including diagnostic criteria and arguments for the classification as an addictive disorder including evidence from neurobiological studies. Based on previous theoretical considerations and empirical findings, this paper examines the use of one recently proposed model, the Interaction of Person-Affect-Cognition-Execution (I-PACE) model, for inspiring future research and for developing new treatment protocols for IGD. The I-PACE model is a theoretical framework that explains symptoms of Internet addiction by looking at interactions between predisposing factors, moderators, and mediators in combination with reduced executive functioning and diminished decision making. Finally, the paper discusses how current treatment protocols focusing on Cognitive-Behavioral Therapy for Internet addiction (CBT-IA) fit with the processes hypothesized in the I-PACE model.

Merging Theoretical Models and Therapy Approaches in the Context of Internet Gaming Disorder: A Personal Perspective

PubMed Central

Young, Kimberly S.; Brand, Matthias

2017-01-01

Although, it is not yet officially recognized as a clinical entity which is diagnosable, Internet Gaming Disorder (IGD) has been included in section III for further study in the DSM-5 by the American Psychiatric Association (APA, 2013). This is important because there is increasing evidence that people of all ages, in particular teens and young adults, are facing very real and sometimes very severe consequences in daily life resulting from an addictive use of online games. This article summarizes general aspects of IGD including diagnostic criteria and arguments for the classification as an addictive disorder including evidence from neurobiological studies. Based on previous theoretical considerations and empirical findings, this paper examines the use of one recently proposed model, the Interaction of Person-Affect-Cognition-Execution (I-PACE) model, for inspiring future research and for developing new treatment protocols for IGD. The I-PACE model is a theoretical framework that explains symptoms of Internet addiction by looking at interactions between predisposing factors, moderators, and mediators in combination with reduced executive functioning and diminished decision making. Finally, the paper discusses how current treatment protocols focusing on Cognitive-Behavioral Therapy for Internet addiction (CBT-IA) fit with the processes hypothesized in the I-PACE model. PMID:29104555

Restoring walking after spinal cord injury: operant conditioning of spinal reflexes can help.

PubMed

Thompson, Aiko K; Wolpaw, Jonathan R

2015-04-01

People with incomplete spinal cord injury (SCI) frequently suffer motor disabilities due to spasticity and poor muscle control, even after conventional therapy. Abnormal spinal reflex activity often contributes to these problems. Operant conditioning of spinal reflexes, which can target plasticity to specific reflex pathways, can enhance recovery. In rats in which a right lateral column lesion had weakened right stance and produced an asymmetrical gait, up-conditioning of the right soleus H-reflex, which increased muscle spindle afferent excitation of soleus, strengthened right stance and eliminated the asymmetry. In people with hyperreflexia due to incomplete SCI, down-conditioning of the soleus H-reflex improved walking speed and symmetry. Furthermore, modulation of electromyographic activity during walking improved bilaterally, indicating that a protocol that targets plasticity to a specific pathway can trigger widespread plasticity that improves recovery far beyond that attributable to the change in the targeted pathway. These improvements were apparent to people in their daily lives. They reported walking faster and farther, and noted less spasticity and better balance. Operant conditioning protocols could be developed to modify other spinal reflexes or corticospinal connections; and could be combined with other therapies to enhance recovery in people with SCI or other neuromuscular disorders. © The Author(s) 2014.

Synergistic effect of combined transcranial direct current stimulation/constraint-induced movement therapy in children and young adults with hemiparesis: study protocol.

PubMed

Gillick, Bernadette; Menk, Jeremiah; Mueller, Bryon; Meekins, Gregg; Krach, Linda E; Feyma, Timothy; Rudser, Kyle

2015-11-12

Perinatal stroke occurs in more than 1 in 2,500 live births and resultant congenital hemiparesis necessitates investigation into interventions which may improve long-term function and decreased burden of care beyond current therapies ( http://www.cdc.gov/ncbddd/cp/data.html ). Constraint-Induced Movement Therapy (CIMT) is recognized as an effective hemiparesis rehabilitation intervention. Transcranial direct current stimulation as an adjunct treatment to CIMT may potentiate neuroplastic responses and improve motor function. The methodology of a clinical trial in children designed as a placebo-controlled, serial -session, non-invasive brain stimulation trial incorporating CIMT is described here. The primary hypotheses are 1) that no serious adverse events will occur in children receiving non-invasive brain stimulation and 2) that children in the stimulation intervention group will show significant improvements in hand motor function compared to children in the placebo stimulation control group. A randomized, controlled, double-blinded clinical trial. Twenty children and/or young adults (ages 8-21) with congenital hemiparesis, will be enrolled. The intervention group will receive ten 2-hour sessions of transcranial direct current stimulation combined with constraint-induced movement therapy and the control group will receive sham stimulation with CIMT. The primary outcome measure is safety assessment of transcranial direct current stimulation by physician evaluation, vital sign monitoring and symptom reports. Additionally, hand function will be evaluated using the Assisting Hand Assessment, grip strength and assessment of goals using the Canadian Occupational Performance Measure. Neuroimaging will confirm diagnoses, corticospinal tract integrity and cortical activation. Motor cortical excitability will also be examined using transcranial magnetic stimulation techniques. Combining non-invasive brain stimulation and CIMT interventions has the potential to improve motor function in children with congenital hemiparesis beyond each intervention independently. Such a combined intervention has the potential to benefit an individual throughout their lifetime. Clinicaltrials.gov, NCT02250092 Registered 18 September 2014.

Cryoultrasound therapy in the treatment of chronic plantar fasciitis with heel spurs. A randomized controlled clinical study.

PubMed

Costantino, C; Vulpiani, M C; Romiti, D; Vetrano, M; Saraceni, V M

2014-02-01

Plantar fasciitis is one of the most common causes of pain in the inferior heel and is very frequent in some running sports. It affects up to 10% of general population and accounts for 11% to 15% of all foot pain symptomatology. Several treatments have been suggested, but there is no evidence supporting a specific conservative management strategy. Evaluation of the efficacy of combined cryoultrasound therapy on chronic plantar fasciitis with heel spurs resistant to pharmacological and instrumental therapies. Single-blind randomized clinical trial. 102 consecutive patients affected by chronic plantar fasciitis with painful symptomatology for at least 6 months, intensity of pain higher than 5 on the VAS score, presence of heel spurs, use of plantar orthoses and ineffectiveness of previous therapies. The patients were randomized into two groups: Group A treated with cryoultrasound therapy and Group B with cryotherapy. Our protocol was based on 10 daily treatments, lasting 20 minutes. Each participant was evaluated using VAS score before (T0) the treatment and 3 months (T1), 12 months (T2) and 18 months (T3) after. Effectiveness index was calculated from T1 to T3. Both treatments have been found effective. The difference in pain intensity on the VAS scale between the two groups at T2 was 4.35 points in favor of Group A (IC 95% 3.75; 4.95; P<0.001), reaching the primary end point. The difference in pain intensity on the VAS scale between the two groups at T1, T2 and T3 was 3.00, 4.35 and 4.81 respectively, showing a statistically significant difference between VAS average scores at all follow-ups in favor of Group A. Scores of at least 66% at the effectiveness index were only achieved in Group A (P values <0.001). Cryoultrasound therapy could be an efficient treatment option for chronic plantar fasciitis. Cryoultrasound therapy promises an effective and long-lasting clinical improvement in patients with chronic plantar fasciitis, granted its high therapeutic efficiency, patients' satisfaction, its limited cost and its short and repeatable protocol of use.

Ozone Therapy in Dentistry

PubMed Central

Domb, William C

2014-01-01

Summary The 21st century dental practice is quite dynamic. New treatment protocols and new materials are being developed at a rapid pace. Ozone dental therapy falls into the category of new treatment protocols in dentistry, yet ozone is not new at all. Ozone therapy is already a major treatment modality in Europe, South America and a number of other countries. What is provided here will not be an exhaustive scientific treatise so much as a brief general introduction into what dentists are now doing with ozone therapies and the numerous oral/systemic links that make this subject so important for physicians so that, ultimately, they may serve their patients more effectively and productively. PMID:25363268

Ozone therapy in dentistry. A brief review for physicians.

PubMed

Domb, William C

2014-10-31

The 21(st) century dental practice is quite dynamic. New treatment protocols and new materials are being developed at a rapid pace. Ozone dental therapy falls into the category of new treatment protocols in dentistry, yet ozone is not new at all. Ozone therapy is already a major treatment modality in Europe, South America and a number of other countries. What is provided here will not be an exhaustive scientific treatise so much as a brief general introduction into what dentists are now doing with ozone therapies and the numerous oral/systemic links that make this subject so important for physicians so that, ultimately, they may serve their patients more effectively and productively.

Sunitinib Plus Androgen Deprivation and Radiation Therapy for Patients With Localized High-Risk Prostate Cancer: Results From a Multi-institutional Phase 1 Study

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

Corn, Paul G., E-mail: pcorn@mdanderson.org; Song, Danny Y.; Heath, Elisabeth

Purpose: To evaluate the feasibility of administering sunitinib in combination with androgen deprivation therapy and external-beam intensity modulated radiation therapy (XRT) in patients with localized high-risk prostate cancer. Methods and Materials: Seventeen men with localized adenocarcinoma of the prostate with cT2c-cT4 or Gleason 8-10 or prostate-specific antigen >20 ng/mL received initial androgen deprivation (leuprolide 22.5 mg every 12 weeks plus oral bicalutamide 50 mg daily) for 4-8 weeks before oral sunitinib 12.5, 25, or 37.5 mg daily for 4 weeks as lead-in, then concurrently with and 4 weeks after XRT (75.6 Gy in 42 fractions to prostate and seminal vesicles).more » A 3+3 sequential dose-escalation design was used to assess the frequency of dose-limiting toxicity (DLT) and establish a maximal tolerated dose of sunitinib. Results: Sunitinib at 12.5- and 25-mg dose levels was well tolerated. The first 4 patients enrolled at 37.5 mg experienced a DLT during lead-in, and a drug interaction between sunitinib and bicalutamide was suspected. The protocol was revised and concurrent bicalutamide omitted. Of the next 3 patients enrolled at 37.5 mg, 2 of 3 receiving concurrent therapy experienced DLTs during radiation: grade 3 diarrhea and grade 3 proctitis, respectively. Only 1 of 7 patients completed sunitinib at 37.5 mg daily, whereas 3 of 3 patients (25 mg as starting dose) and 3 of 4 patients (25 mg as reduced dose) completed therapy. Conclusions: The feasibility of combined vascular endothelial growth factor receptor (VEGFR)/platelet-derived growth factor receptor (PDGFR) inhibitor therapy, androgen deprivation, and radiation therapy for prostate cancer was established. Using a daily dosing regimen with lead-in, concurrent, and post-XRT therapy, the recommended phase 2 dose of sunitinib is 25 mg daily.« less

Economic evaluation of an intensive group training protocol compared with usual care physiotherapy in patients with chronic low back pain.

PubMed

van der Roer, Nicole; van Tulder, Maurits; van Mechelen, Willem; de Vet, Henrica

2008-02-15

Economic evaluation from a societal perspective conducted alongside a randomized controlled trial with a follow-up of 52 weeks. To evaluate the cost effectiveness and cost utility of an intensive group training protocol compared with usual care physiotherapy in patients with nonspecific chronic low back pain. The intensive group training protocol combines exercise therapy, back school, and behavioral principles. Two studies found a significant reduction in absenteeism for a graded activity program in occupational health care. This program has not yet been evaluated in a primary care physiotherapy setting. Participating physical therapists in primary care recruited 114 patients with chronic nonspecific low back pain. Eligible patients were randomized to either the protocol group or the guideline group. Outcome measures included functional status (Roland Morris Disability Questionnaire), pain intensity (11-point numerical rating scale), general perceived effect and quality of life (EuroQol-5D). Cost data were measured with cost diaries and included direct and indirect costs related to low back pain. After 52 weeks, the direct health care costs were significantly higher for patients in the protocol group, largely due to the costs of the intervention. The mean difference in total costs amounted to [Euro sign] 233 (95% confidence interval: [Euro sign] -2.185; [Euro sign] 2.764). The cost-effectiveness planes indicated no significant differences in cost effectiveness between the 2 groups. The results of this economic evaluation showed no difference in total costs between the protocol group and the guideline group. The differences in effects were small and not statistically significant. At present, national implementation of the protocol is not recommended.

Intensive group training protocol versus guideline physiotherapy for patients with chronic low back pain: a randomised controlled trial.

PubMed

van der Roer, Nicole; van Tulder, Maurits; Barendse, Johanna; Knol, Dirk; van Mechelen, Willem; de Vet, Henrica

2008-09-01

Intensive group training using principles of graded activity has been proven to be effective in occupational care for workers with chronic low back pain. Objective of the study was to compare the effects of an intensive group training protocol aimed at returning to normal daily activities and guideline physiotherapy for primary care patients with non-specific chronic low back pain. The study was designed as pragmatic randomised controlled trial with a setup of 105 primary care physiotherapists in 49 practices and 114 patients with non-specific low back pain of more than 12 weeks duration participated in the study. In the intensive group training protocol exercise therapy, back school and operant-conditioning behavioural principles are combined. Patients were treated during 10 individual sessions along 20 group sessions. Usual care consisted of physiotherapy according to the Dutch guidelines for Low Back Pain. Main outcome measures were functional disability (Roland Morris disability questionnaire), pain intensity, perceived recovery and sick leave because of low back pain assessed at baseline and after 6, 13, 26 and 52 weeks. Both an intention-to-treat analysis and a per-protocol analysis were performed. Multilevel analysis did not show significant differences between both treatment groups on any outcome measures during the complete follow-up period, with one exception. After 26 weeks the protocol group showed more reduction in pain intensity than the guideline group, but this difference was absent after 52 weeks. We finally conclude that an intensive group training protocol was not more effective than usual physiotherapy for chronic low back pain.

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

New anabolic therapies in osteoporosis.

PubMed

Rubin, Mishaela R; Bilezikian, John P

2003-03-01

Anabolic agents represent an important new advance in the therapy of osteoporosis. Their potential might be substantially greater than the anti-resorptives. Because the anti-resorptives and anabolic agents work by completely distinct mechanisms of action, it is possible that the combination of agents could be significantly more potent than either agent alone. Recent evidence suggests that a plateau in BMD might occur after prolonged exposure to PTH. Anti-resorptive therapy during or after anabolic therapy might prevent this skeletal adaptation. Protocols to consider anabolic agents as intermittent recycling therapy would be of interest. Of all the anabolics, PTH is the most promising. However, there are unanswered questions about PTH. More studies are needed to document an anabolic effect on cortical bone. More large-scale studies are needed to further determine the reduction in nonvertebral fractures with PTH, especially at the hip. In the future, PTH is likely to be modified for easier and more targeted delivery. Oral or transdermal delivery systems may become available. Recently, Gowen et al have described an oral calcilytic molecule that antagonizes the parathyroid cell calcium receptor, thus stimulating the endogenous release of PTH. This approach could represent a novel endogenous delivery system for intermittent PTH administration. Rising expectations that anabolic therapies for osteoporosis will soon play a major role in treating this disease are likely to fuel further studies and the development of even more novel approaches to therapy.

Comparative effectiveness of vildagliptin in combination with other oral anti-diabetes agents in usual-care conditions: the EDGE-Latin America study.

PubMed

Mendivil, Carlos O; Márquez-Rodríguez, Eduardo; Angel, Iván D; Paz, Gustavo; Rodríguez, Cruz; Almada, Jorge; Szyskowsky, Ofelia

2014-09-01

To assess the proportion of patients on vildagliptin add-on dual therapy who respond to treatment over a 12 month follow-up, relative to comparator oral anti-diabetes dual therapy, in a usual care setting. Participants were patients with type 2 diabetes (T2DM) aged 18 years and older from 311 centers in Argentina, Colombia, Ecuador, Mexico and Venezuela. Patients were taking monotherapy with an oral anti-diabetes drug (OAD), and were prescribed a new add-on OAD based on the judgment of their personal physician. According to this choice, patients were assigned to one of the two cohorts: vildagliptin or comparator OADs. The primary endpoint was the proportion of patients achieving an A1c drop >0.3% without edema, hypoglycemia, weight gain or discontinuation due to gastrointestinal (GI) events. The secondary endpoint was the proportion of patients with baseline A1c ≥7% who reached the goal of an A1c <7% without hypoglycemia or weight gain. The per-protocol population (a subset of the intention-to-treat population that excluded patients with pre-specified protocol deviations) comprised 3773 patients, 3002 in the vildagliptin cohort and 771 in the comparator cohort. The proportion of patients reaching the primary endpoint was higher in the vildagliptin cohort (60.3%) than the comparator cohort (50.7%), OR 1.48 (95% CI: 1.25-1.73). The same was observed for the secondary endpoint (44.8 versus 33.1%) OR 1.64 (95% CI: 1.37-1.98). The incidence of adverse events was low and similar between treatment cohorts. In a usual care setting, patients treated with a vildagliptin combination succeeded in lowering A1c to <7%, without weight gain, hypoglycemia or peripheral edema more often than patients treated with comparator combinations, without increased risk of adverse events. Key limitations are the observational nature of the study and its relatively limited 12 month timeframe.

Hepatic sinusoidal obstruction syndrome during maintenance therapy of childhood acute lymphoblastic leukemia is associated with continuous asparaginase therapy and mercaptopurine metabolites.

PubMed

Toksvang, Linea Natalie; De Pietri, Silvia; Nielsen, Stine N; Nersting, Jacob; Albertsen, Birgitte K; Wehner, Peder S; Rosthøj, Steen; Lähteenmäki, Päivi M; Nilsson, Daniel; Nystad, Tove A; Grell, Kathrine; Frandsen, Thomas L; Schmiegelow, Kjeld

2017-09-01

Hepatic sinusoidal obstruction syndrome (SOS) during treatment of childhood acute lymphoblastic leukemia (ALL) has mainly been associated with 6-thioguanine. The occurrence of several SOS cases after the introduction of extended pegylated asparaginase (PEG-asparaginase) therapy in the Nordic Society of Paediatric Haematology and Oncology (NOPHO) ALL2008 protocol led us to hypothesize that PEG-asparaginase, combined with other drugs, may trigger SOS during 6-thioguanine-free maintenance therapy. In children with ALL treated in Denmark according to the NOPHO ALL2008 protocol, we investigated the risk of SOS during methotrexate (MTX)/6-mercaptopurine (6MP) maintenance therapy that included PEG-asparaginase until week 33 (randomized to two- vs. six-week intervals), as well as alternating high-dose MTX or vincristine/dexamethasone pulses every four weeks. Among 130 children receiving PEG-asparaginase biweekly, 29 developed SOS (≥2 criteria: hyperbilirubinemia, hepatomegaly, ascites, weight gain ≥2.5%, unexplained thrombocytopenia <75 × 10 9 l -1 ) at a median of 30 days (interquartile range [IQR]: 17-66) into maintenance (cumulative incidence: 27%). SOS cases fulfilling one, two, or three Ponte di Legno criteria were classified as possible (n = 2), probable (n = 8), or verified (n = 19) SOS, respectively. Twenty-six cases (90%) occurred during PEG-asparaginase treatment, including 21 (81%) within 14 days from the last chemotherapy pulse compared with the subsequent 14 days (P = 0.0025). Cytotoxic 6MP metabolites were significantly higher on PEG-asparaginase compared to after its discontinuation. Time-dependent Cox regression analysis showed increased SOS hazard ratio (HR) for erythrocyte levels of methylated 6MP metabolites (HR: 1.09 per 1,000 nmol/mmol hemoglobin increase, 95% confidence interval: 1.05-1.14). Six-week PEG-asparaginase intervals significantly reduced SOS-specific hazards (P < 0.01). PEG-asparaginase increases cytotoxic 6MP metabolite levels and risk of SOS, potentially interacting with other chemotherapy pulses. © 2017 Wiley Periodicals, Inc.

Developing protocols for recombinant adeno-associated virus-mediated gene therapy in space.

PubMed

Ohi, S

2000-07-01

With the advent of the era of International Space Station (ISS) and Mars exploration, it is important more than ever to develop means to cure genetic and acquired diseases, which include cancer and AIDS, for these diseases hamper human activities. Thus, our ultimate goal is to develop protocols for gene therapy, which are suitable to humans on the earth as well as in space. Specifically, we are trying to cure the hemoglobinopathies, beta-thalassemia (Cooley's anemia) and sickle cell anemia, by gene therapy. These well-characterized molecular diseases serve as models for developing ex vivo gene therapy, which would apply to other disorders as well. For example, the procedure may become directly relevant to treating astronauts for space-anemia, immune suppression and bone marrow derived tumors, e.g. leukemia. The adeno-associated virus serotype 2 (AAV2) is a non-pathogenic human parvovirus with broad host-range and tissue specificity. Exploiting these characteristics we have been developing protocols for recombinant AAV2 (rAAV)-based gene therapy. With the rAAV constructs and hematopoietic stem cell (HSC) culture systems in hand, we are currently attempting to cure the mouse model of beta-thalassemia [C57BL/6- Hbbth/Hbbth, Hb(d-minor)] by HSC transplantation (HST) as well as by gene therapy. This paper describes the current status of our rAAV-gene therapy research.

Cost analysis of negative-pressure wound therapy with instillation for wound bed preparation preceding split-thickness skin grafts for massive (>100 cm(2)) chronic venous leg ulcers.

PubMed

Yang, C Kevin; Alcantara, Sean; Goss, Selena; Lantis, John C

2015-04-01

Massive (≥100 cm(2)) venous leg ulcers (VLUs) demonstrate very low closure rates with standard compression therapy and are costly to manage. Negative-pressure wound therapy (NPWT), followed by a split-thickness skin graft (STSG), can be a cost-effective alternative to this standard care. We performed a cost analysis of these two treatments. A retrospective review was performed of 10 ulcers treated with surgical debridement, 7 days of inpatient NPWT with topical antiseptic instillation (NPWTi), and STSG, with 4 additional days of inpatient NPWT bolster over the graft. Independent medical cost estimators were used to compare the cost of this treatment protocol with standard outpatient compression therapy. The average length of time ulcers were present before patients entered the study was 38 months (range, 3-120 months). Eight of 10 patients had complete VLU closure by 6 months after NPWTi with STSG. The 6-month costs of the proposed treatment protocol and standard twice-weekly compression therapy were estimated to be $27,000 and $28,000, respectively. NPWTi with STSG treatment is more effective for closure of massive VLUs at 6 months than that reported for standard compression therapy. Further, the cost of the proposed treatment protocol is comparable with standard compression therapy. Copyright © 2015 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

Generation of genetic constructs that simultaneously express several shRNAs.

PubMed

Kretova, Olga V; Alembekov, Ildar R; Tchurikov, Nickolai A

2012-05-01

RNAi has potential as an antiviral gene therapy strategy. Cassette constructs simultaneously expressing several siRNAs could prove to be the most efficient technique in developing gene therapy approaches for highly mutable viruses such as HIV-1. Here we describe a rapid and cost-saving protocol to generate cassettes that simultaneously express three siRNAs for repression of HIV-1 and CCR5 transcripts. siRNA biological activity was tested in a non-viral system, and exhibited both efficiency and specificity. Our results suggest this protocol can be used to rapidly generate cassette constructs for antiviral gene therapy applications.

Impairment of liver synthetic function and the production of plasma proteins in primary breast cancer patients on doxorubicincyclophosphamide (AC) protocol.

PubMed

Saleem, Zikria; Ahmad, Mobasher; Hashmi, Furqan Khurshid; Saeed, Hamid; Aziz, Muhammad Tahir

2016-09-01

Doxorubicin and Cyclophosphamide (AC protocol) combination is usually considered as a first line therapy in newly diagnosed breast cancer patients. Thus, a retrospective observational study was conducted to monitor the effect of AC protocol on liver synthetic functions and production of plasma proteins in breast cancer patients, reporting to specialized cancer care hospital of Lahore, Pakistan. A total of 75 patients (n=75) on AC protocol with breast cancer were observed in this study. The patient data including age, gender, body surface area, dosage, disease status and laboratory biochemical values were recorded by reviewing historical treatment records. Pre-treatment values were taken as baseline values for albumin, globulin, blood urea nitrogen (BUN), albumin/globulin (A/G) ratio and total proteins. The baseline values were compared after each cycle of by applying ANOVA using statistical tool SPSS® version 21. The plasma levels of blood urea nitrogen (BUN), total protein and globulin dropped significantly (p<0.05) in patients of all age groups. However, the albumin levels were not significantly changed (p>0.05). The A/G ratio level increased (p<0.05) as a result of reduction in globulin levels. Significant changes in plasma protein levels were observed in the elderly patients (50 to 65 years) than patients between 20 to 50 years of age. AC protocol impairs liver synthetic functions as observed by decreased blood urea nitrogen (BUN) and plasma protein levels.

The costs and cost-effectiveness of an integrated sepsis treatment protocol.

PubMed

Talmor, Daniel; Greenberg, Dan; Howell, Michael D; Lisbon, Alan; Novack, Victor; Shapiro, Nathan

2008-04-01

Sepsis is associated with high mortality and treatment costs. International guidelines recommend the implementation of integrated sepsis protocols; however, the true cost and cost-effectiveness of these are unknown. To assess the cost-effectiveness of an integrated sepsis protocol, as compared with conventional care. Prospective cohort study of consecutive patients presenting with septic shock and enrolled in the institution's integrated sepsis protocol. Clinical and economic outcomes were compared with a historical control cohort. Beth Israel Deaconess Medical Center. Overall, 79 patients presenting to the emergency department with septic shock in the treatment cohort and 51 patients in the control group. An integrated sepsis treatment protocol incorporating empirical antibiotics, early goal-directed therapy, intensive insulin therapy, lung-protective ventilation, and consideration for drotrecogin alfa and steroid therapy. In-hospital treatment costs were collected using the hospital's detailed accounting system. The cost-effectiveness analysis was performed from the perspective of the healthcare system using a lifetime horizon. The primary end point for the cost-effectiveness analysis was the incremental cost per quality-adjusted life year gained. Mortality in the treatment group was 20.3% vs. 29.4% in the control group (p = .23). Implementing an integrated sepsis protocol resulted in a mean increase in cost of approximately $8,800 per patient, largely driven by increased intensive care unit length of stay. Life expectancy and quality-adjusted life years were higher in the treatment group; 0.78 and 0.54, respectively. The protocol was associated with an incremental cost of $11,274 per life-year saved and a cost of $16,309 per quality-adjusted life year gained. In patients with septic shock, an integrated sepsis protocol, although not cost-saving, appears to be cost-effective and compares very favorably to other commonly delivered acute care interventions.

Quality and Variability of Online Available Physical Therapy Protocols From Academic Orthopaedic Surgery Programs for Anterior Cruciate Ligament Reconstruction.

PubMed

Makhni, Eric C; Crump, Erica K; Steinhaus, Michael E; Verma, Nikhil N; Ahmad, Christopher S; Cole, Brian J; Bach, Bernard R

2016-08-01

To assess the quality and variability found across anterior cruciate ligament (ACL) rehabilitation protocols published online by academic orthopaedic programs. Web-based ACL physical therapy protocols from United States academic orthopaedic programs available online were included for review. Main exclusion criteria included concomitant meniscus repair, protocols aimed at pediatric patients, and failure to provide time points for the commencement or recommended completion of any protocol components. A comprehensive, custom scoring rubric was created that was used to assess each protocol for the presence or absence of various rehabilitation components, as well as when those activities were allowed to be initiated in each protocol. Forty-two protocols were included for review from 155 U.S. academic orthopaedic programs. Only 13 protocols (31%) recommended a prehabilitation program. Five protocols (12%) recommended continuous passive motion postoperatively. Eleven protocols (26%) recommended routine partial or non-weight bearing immediately postoperatively. Ten protocols (24%) mentioned utilization of a secondary/functional brace. There was considerable variation in range of desired full-weight-bearing initiation (9 weeks), as well as in the types of strength and proprioception exercises specifically recommended. Only 8 different protocols (19%) recommended return to sport after achieving certain strength and activity criteria. Many ACL rehabilitation protocols recommend treatment modalities not supported by current reports. Moreover, high variability in the composition and time ranges of rehabilitation components may lead to confusion among patients and therapists. Level II. Copyright © 2016 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

Comparison of COAP and UW-19 protocols for dogs with multicentric lymphoma.

PubMed

Hosoya, Kenji; Kisseberth, William C; Lord, Linda K; Alvarez, Francisco J; Lara-Garcia, Ana; Kosarek, Carrie E; London, Cheryl A; Couto, C Guillermo

2007-01-01

Various chemotherapy protocols for treating lymphoma in dogs have been published; however, comparison of protocols from different studies is difficult, especially when evaluating survival time and toxicoses. The choice of COAP (C, cyclophosphamide; O, vincristine; A, cytosine arabinoside; P, prednisone) and a modified University of Wisconsin 19-week (UW-19) induction protocol has no influence on overall survival times in dogs with lymphoma. One hundred and one dogs with multicentric lymphoma. Retrospective study (2001-2006). Dogs induced with either an 8-week COP-based protocol (C, cyclophosphamide; O, vincristine; and P, prednisone) with maintenance therapy (COAP group) or a 19-week CHOP (C, cyclophosphamide; H, doxorubicin; O, vincristine; and P, prednisone) based protocol (UW-19 group) were compared in terms of the duration of first remission, survival time, toxicoses, and cost. There were 71 dogs in the COAP group and 30 dogs in the UW-19 group. Various protocols were used after the first relapse. The median duration of the first remission for the COAP and UW-19 groups were 94 days (range, 6-356 days) and 174 days (28-438 days), respectively (P < .01). The median survival times for dogs in the COAP and UW-19 groups were 309 days (6-620 days) and 275 days (70-1102+ days), respectively (P = .09). Dogs in the COAP group had a hazard ratio of 1.9 (95% CI 1.1-3.4) for death relative to the UW-19 group (P = .03), after controlling for the confounders (World Health Organization clinical stage, age, sex, use of doxorubicin during reinduction). The severity of neutropenia and gastrointestinal toxicoses were significantly higher in the UW-19 group than in the COAP group (P = .01 and P < .01, respectively). Use of a long-term doxorubicin-containing sequential combination chemotherapy protocol is associated with a decreased risk of relapse and death relative to a non-doxorubicin-containing protocol.

10 CFR 35.457 - Therapy-related computer systems.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 10 Energy 1 2014-01-01 2014-01-01 false Therapy-related computer systems. 35.457 Section 35.457... Therapy-related computer systems. The licensee shall perform acceptance testing on the treatment planning system of therapy-related computer systems in accordance with published protocols accepted by nationally...

10 CFR 35.457 - Therapy-related computer systems.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 10 Energy 1 2012-01-01 2012-01-01 false Therapy-related computer systems. 35.457 Section 35.457... Therapy-related computer systems. The licensee shall perform acceptance testing on the treatment planning system of therapy-related computer systems in accordance with published protocols accepted by nationally...

10 CFR 35.457 - Therapy-related computer systems.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 10 Energy 1 2013-01-01 2013-01-01 false Therapy-related computer systems. 35.457 Section 35.457... Therapy-related computer systems. The licensee shall perform acceptance testing on the treatment planning system of therapy-related computer systems in accordance with published protocols accepted by nationally...

10 CFR 35.457 - Therapy-related computer systems.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 1 2010-01-01 2010-01-01 false Therapy-related computer systems. 35.457 Section 35.457... Therapy-related computer systems. The licensee shall perform acceptance testing on the treatment planning system of therapy-related computer systems in accordance with published protocols accepted by nationally...

10 CFR 35.457 - Therapy-related computer systems.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 1 2011-01-01 2011-01-01 false Therapy-related computer systems. 35.457 Section 35.457... Therapy-related computer systems. The licensee shall perform acceptance testing on the treatment planning system of therapy-related computer systems in accordance with published protocols accepted by nationally...

Treatment algorithms and protocolized care.

PubMed

Morris, Alan H

2003-06-01

Excess information in complex ICU environments exceeds human decision-making limits and likely contributes to unnecessary variation in clinical care, increasing the likelihood of clinical errors. I reviewed recent critical care clinical trials searching for information about the impact of protocol use on clinically pertinent outcomes. Several recently published clinical trials illustrate the importance of distinguishing efficacy and effectiveness trials. One of these trials illustrates the danger of conducting effectiveness trials before the efficacy of an intervention is established. The trials also illustrate the importance of distinguishing guidelines and inadequately explicit protocols from adequately explicit protocols. Only adequately explicit protocols contain enough detail to lead different clinicians to the same decision when faced with the same clinical scenario. Differences between guidelines and protocols are important. Guidelines lack detail and provide general guidance that requires clinicians to fill in many gaps. Computerized or paper-based protocols are detailed and, when used for complex clinical ICU problems, can generate patient-specific, evidence-based therapy instructions that can be carried out by different clinicians with almost no interclinician variability. Individualization of patient therapy can be preserved by these protocols when they are driven by individual patient data. Explicit decision-support tools (eg, guidelines and protocols) have favorable effects on clinician and patient outcomes and can reduce the variation in clinical practice. Guidelines and protocols that aid ICU decision makers should be more widely distributed.

The Effects of Alternative Resuscitation Strategies on Acute Kidney Injury in Patients with Septic Shock.

PubMed

Kellum, John A; Chawla, Lakhmir S; Keener, Christopher; Singbartl, Kai; Palevsky, Paul M; Pike, Francis L; Yealy, Donald M; Huang, David T; Angus, Derek C

2016-02-01

Septic shock is a common cause of acute kidney injury (AKI), and fluid resuscitation is a major part of therapy. To determine if structured resuscitation designed to alter fluid, blood, and vasopressor use affects the development or severity of AKI or outcomes. Ancillary study to the ProCESS (Protocolized Care for Early Septic Shock) trial of alternative resuscitation strategies (two protocols vs. usual care) for septic shock. We studied 1,243 patients and classified AKI using serum creatinine and urine output. We determined recovery status at hospital discharge, examined rates of renal replacement therapy and fluid overload, and measured biomarkers of kidney damage. Among patients without evidence of AKI at enrollment, 37.6% of protocolized care and 38.1% of usual care patients developed kidney injury (P = 0.90). AKI duration (P = 0.59) and rates of renal replacement therapy did not differ between study arms (6.9% for protocolized care and 4.3% for usual care; P = 0.08). Fluid overload occurred in 8.3% of protocolized care and 6.3% of usual care patients (P = 0.26). Among patients with severe AKI, complete and partial recovery was 50.7 and 13.2% for protocolized patients and 49.1 and 13.4% for usual care patients (P = 0.93). Sixty-day hospital mortality was 6.2% for patients without AKI, 16.8% for those with stage 1, and 27.7% for stages 2 to 3. In patients with septic shock, AKI is common and associated with adverse outcomes, but it is not influenced by protocolized resuscitation compared with usual care.

Therapeutic efficacy of artesunate-amodiaquine and artemether-lumefantrine combinations in the treatment of uncomplicated malaria in two ecological zones in Ghana.

PubMed

Abuaku, Benjamin; Duah, Nancy; Quaye, Lydia; Quashie, Neils; Malm, Keziah; Bart-Plange, Constance; Koram, Kwadwo

2016-01-05

Case management based on prompt diagnosis and adequate treatment using artemisinin-based combination therapy (ACT) remains the main focus of malaria control in Ghana. As part of routine surveillance on the therapeutic efficacy of ACT in Ghana, the efficacy of amodiaquine-artesunate (AS-AQ) and artemether-lumefantrine (AL) were studied in six sentinel sites representing the forest and savannah zones of the country. Three sites representing the two ecological zones studied AS-AQ whilst the other three sites studied AL. In each site, the study was a one-arm prospective evaluation of the clinical, parasitological, and haematological responses to directly observed therapy for uncomplicated malaria with either AS-AQ or AL among children aged 6 months and 9 years. The WHO 2009 protocol for monitoring anti-malarial drug efficacy was used for the study between July 2013 and March 2014. Per-protocol analyses on day 28 showed an overall PCR-corrected cure rate of 100% for AS-AQ and 97.6% (95% CI 93.1, 99.5) for AL: 97.2% (95% CI 92.0, 99.4) in the forest zone and 100% in the savannah zone. Kaplan-Meier survival analysis showed similar outcomes. Prevalence of fever decreased by about 75% after the first day of treatment with each ACT in the two ecological zones. No child studied was parasitaemic on day 3, and gametocytaemia was generally maintained at low levels (<5%). Post-treatment mean haemoglobin concentrations significantly increased in the two ecological zones. Therapeutic efficacy of AS-AQ and AL remains over 90% in the forest and savannah zones of Ghana. Additionally, post-treatment parasitaemia on day 3 is rare suggesting that artemisinin is still efficacious in Ghana.

Towards consistent generation of pancreatic lineage progenitors from human pluripotent stem cells.

PubMed

Rostovskaya, Maria; Bredenkamp, Nicholas; Smith, Austin

2015-10-19

Human pluripotent stem cells can in principle be used as a source of any differentiated cell type for disease modelling, drug screening, toxicology testing or cell replacement therapy. Type I diabetes is considered a major target for stem cell applications due to the shortage of primary human beta cells. Several protocols have been reported for generating pancreatic progenitors by in vitro differentiation of human pluripotent stem cells. Here we first assessed one of these protocols on a panel of pluripotent stem cell lines for capacity to engender glucose sensitive insulin-producing cells after engraftment in immunocompromised mice. We observed variable outcomes with only one cell line showing a low level of glucose response. We, therefore, undertook a systematic comparison of different methods for inducing definitive endoderm and subsequently pancreatic differentiation. Of several protocols tested, we identified a combined approach that robustly generated pancreatic progenitors in vitro from both embryo-derived and induced pluripotent stem cells. These findings suggest that, although there are intrinsic differences in lineage specification propensity between pluripotent stem cell lines, optimal differentiation procedures may consistently direct a substantial fraction of cells into pancreatic specification. © 2015 The Authors.

Stem cell-derived kidney cells and organoids: Recent breakthroughs and emerging applications.

PubMed

Chuah, Jacqueline Kai Chin; Zink, Daniele

The global rise in the numbers of kidney patients and the shortage in transplantable organs have led to an increasing interest in kidney-specific regenerative therapies, renal disease modelling and bioartificial kidneys. Sources for large quantities of high-quality renal cells and tissues would be required, also for applications in in vitro platforms for compound safety and efficacy screening. Stem cell-based approaches for the generation of renal-like cells and tissues would be most attractive, but such methods were not available until recently. This situation has drastically changed since 2013, and various protocols for the generation of renal-like cells and precursors from pluripotent stem cells (PSC) have been established. The most recent breakthroughs were related to the establishment of various protocols for the generation of PSC-derived kidney organoids. In combination with recent advances in genome editing, bioprinting and the establishment of predictive renal screening platforms this results in exciting new possibilities. This review will give a comprehensive overview over current PSC-based protocols for the generation of renal-like cells, precursors and organoids, and their current and potential applications in regenerative medicine, compound screening, disease modelling and bioartificial organs. Copyright © 2016 Elsevier Inc. All rights reserved.

Antibody-based detection of protein phosphorylation status to track the efficacy of novel therapies using nanogram protein quantities from stem cells and cell lines.

PubMed

Aspinall-O'Dea, Mark; Pierce, Andrew; Pellicano, Francesca; Williamson, Andrew J; Scott, Mary T; Walker, Michael J; Holyoake, Tessa L; Whetton, Anthony D

2015-01-01

This protocol describes a highly reproducible antibody-based method that provides protein level and phosphorylation status information from nanogram quantities of protein cell lysate. Nanocapillary isoelectric focusing (cIEF) combines with UV-activated linking chemistry to detect changes in phosphorylation status. As an example application, we describe how to detect changes in response to tyrosine kinase inhibitors (TKIs) in the phosphorylation status of the adaptor protein CrkL, a major substrate of the oncogenic tyrosine kinase BCR-ABL in chronic myeloid leukemia (CML), using highly enriched CML stem cells and mature cell populations in vitro. This protocol provides a 2.5 pg/nl limit of protein detection (<0.2% of a stem cell sample containing <10(4) cells). Additional assays are described for phosphorylated tyrosine 207 (pTyr207)-CrkL and the protein tyrosine phosphatase PTPRC/CD45; these assays were developed using this protocol and applied to CML patient samples. This method is of high throughput, and it can act as a screen for in vitro cancer stem cell response to drugs and novel agents.

Protocol of a prospective study for the combination treatment of Shu-Gan-jian-Pi decoction and steroid standard therapy in autoimmune hepatitis patients.

PubMed

Chi, Xiao-Ling; Xiao, Huan-Ming; Xie, Yu-Bao; Cai, Gao-Shu; Jiang, Jun-Min; Tian, Guang-Jun; Shi, Mei-Jie; Wu, Shu-Duo; Zhao, Peng-Tao; Chen, Hui-Jun

2016-12-07

Prednisone plus azathioprine is considered the mainstay of therapy in the current recommendations for autoimmune hepatitis (AIH). However, it does not provide good benefits for AIH patients because of its serious side effects. Therefore, more and more AIH patients prefer to seek for traditional Chinese medicine (TCM) to manage their symptoms and reduce the side effects of steroids in China. Shu-Gan-Jian-Pi Decoction is a popular used Chinese herbal formula in Guangdong province of China, which has demonstrated the effect of improving efficacy and reducing side effects of corticosteroids in AIH patients. The aim of this study is to evaluate the effects of Shu-Gan-Jian-Pi Decoction combined with steroid in AIH patients. So, this study aims to explore whether the combination treatment of Shu-Gan-Jian-Pi Decoction and steroid standard therapy could improve the clinical management of AIH. A prospective non-randomized study on AIH will be conducted between October 2015 and June 2017 in Guangdong Provincial hospital of Chinese medicine. Eligible AIH patients will be classified as the case group (n = 66) and the control group (n = 66) based on the interventions. Patients taking Shu-Gan-Jian-Pi Decoction combined with prednisone and azathioprine will be in the case group and those taking prednisone and azathioprine will be in the control group. The whole study will last 48 weeks, including a 24-week observation period and a 24-week follow-up period. The primary outcome was complete response to therapy, defined as complete biochemical remission at the patient's last visit of observation period and the absence of predefined steroid-specific side effects throughout treatment. This trial will evaluate the efficacy and safety of Shu-Gan-Jian-Pi Decoction combined with prednisone and azathioprine on AIH patients. The achievement of this trial will provide evidence-based data for Shu-Gan-Jian-Pi Decoction, which could provide good benefits for AIH patients. Chinese Clinical Trial Registry: ChiCTR-OOC-15006155 . Registration date: 28 March 2015.

Deep massage to posterior calf muscles in combination with neural mobilization exercises as a treatment for heel pain: a pilot randomized clinical trial.

PubMed

Saban, Bernice; Deutscher, Daniel; Ziv, Tomer

2014-04-01

Plantar heel pain syndrome (PHPS) is a common foot disorder; however, there is limited clinical evidence on which to base treatment. Repeated clinical observations indicating heel pain during heel rise and minisquat on the affected leg, involving activation of posterior calf muscles, formed the basis of this study. To compare deep massage therapy to posterior calf muscles and neural mobilization with a self-stretch exercise program (DMS) to a common treatment protocol of ultrasound therapy to the painful heel area with the same self-stretch exercises (USS). Patients with PHPS were assigned to a program of 8 treatments over a period of 4-6 weeks in a single-blind randomized clinical trial. Functional status (FS) at admission and discharge from therapy as measured by the Foot & Ankle Computerized Adaptive Test was the main outcome measure. Sixty-nine patients were included in the trial (mean age 53, standard deviation (SD) 13, range 25-86, 57% women), 36 received DMS treatment and 33 with USS. The overall group-by-time interaction for the mixed-model analysis of variance (ANOVA) was found statistically significant (p=0.034), with a change of (mean (confidence interval, CI)) 15 (9-21) and 6 (1-11) FS points for the DMS and USS groups, respectively. Data indicated that both treatment protocols resulted in an overall short-term improvement, however, DMS treatment was significantly more effective in treating PHPS than USS treatment. Copyright © 2013 Elsevier Ltd. All rights reserved.

Management of mal de debarquement syndrome as vestibular migraines.

PubMed

Ghavami, Yaser; Haidar, Yarah M; Ziai, Kasra N; Moshtaghi, Omid; Bhatt, Jay; Lin, Harrison W; Djalilian, Hamid R

2017-07-01

Mal de debarquement syndrome (MdDS) is a balance disorder that typically starts after an extended exposure to passive motion, such as a boat or plane ride. Management is typically supportive (e.g. physical therapy), and symptoms that persist beyond 6 months have been described as unlikely to remit. This study was conducted to evaluate the response of patients with MdDS to management with migraine prophylaxis, including lifestyle changes and medical therapy. Prospective review. Ambulatory setting at a tertiary care medical center. Clinical history, detailed questionnaires, and audiograms were used to diagnose patients with MdDS. Those patients with the diagnosis of the MdDS were placed on our institutional vestibular migraine management protocol. Treatment response was assessed with a quality-of-life (QOL) survey and visual analog scale. Fifteen patients were diagnosed with MdDS, with a predominance of females (73%) and a mean age of 50 ± 13 years. Eleven patients (73%) responded well to management with a vestibular migraine protocol, which included lifestyle changes, as well as pharmacotherapy with verapamil, nortriptyline, topiramate, or a combination thereof. In comparison, a retrospective control group of 17 patients demonstrated a lower rate of improvement when treated with vestibular rehabilitation and physical therapy. Management of MdDS as vestibular migraine can improve patients' symptoms and increase the QOL. Nearly all the patients suffering from MdDS had a personal or family history of migraine headaches or had signs or symptoms suggestive of atypical migraine. 4 Laryngoscope, 127:1670-1675, 2017. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

The role of alternative and natural agents, cryotherapy, and/or laser for management of alimentary mucositis.

PubMed

Migliorati, Cesar A; Oberle-Edwards, Loree; Schubert, Mark

2006-06-01

To review the literature and update the current guidelines of alternative/natural agents, cryotherapy, and/or laser therapy in the management of alimentary mucositis (AM). The original guidelines developed by the Multinational Association for Supportive Care in Cancer (MASCC)/International Society for Oral Oncology (ISOO) mucositis study group were the basis for this study. A medical librarian conducted an initial Medline search to identify research articles published between 2002 and 2005 in English language. A search term combination that included stomatitis, mucositis, mucous membrane, neoplasm, lasers, complimentary therapies, amino acids, antioxidants, vitamins, minerals, plant extracts, and cryotherapy was conducted. This initial search identified articles with a strong scientific methodology that included both preclinical and clinical research. Using standardized scoring forms, authors reviewed and scored individual articles. A consensus result of the review was achieved in a meeting of reviewers in June of 2005. The initial search identified a total of 167 new articles. Of these, 14 were selected and reviewed: alternative/natural therapy (one preclinical study); cryotherapy (four clinical studies); lasers (two clinical studies); and alternative/natural agents (seven clinical studies). A new guideline could be established for the use of cryotherapy in the management of AM in hematopoietic stem cell transplant (HSCT) patients receiving melphalan in the conditioning phase. The rapid progress in the understanding of AM created a need for new prevention and management protocols. Frequent literature review is now necessary to identify agents and protocols being developed in this important area of supportive care in cancer.

Cognitive Behavioral Therapy, Mindfulness, and Hypnosis as Treatment Methods for Generalized Anxiety Disorder.

PubMed

Daitch, Carolyn

2018-07-01

Individuals suffering from generalized anxiety disorder (GAD) experience a broad range of physical, emotional, and cognitive distress. A hallmark of GAD is anxiety around making decisions. Many clinicians notice improvements in patients through specific modalities, such as mindfulness, hypnosis, and cognitive behavioral therapy (CBT); however, these individual methods sometimes fall short. Clinicians and researchers alike note that it can be more effective to combine these three methods into an integrative treatment protocol. This article demonstrates the efficacy of an integrative model through the case study of a client who suffers from GAD and acute fear of decision making. Competent use of mindfulness, hypnosis, and CBT helps the client build the skills necessary to self-soothe, diminish worry, access resources, and enhance hope for the future. Through the article, clinicians interested in integrated treatment models will gain insight into how to apply these methods.

Novel vaccines for glioblastoma: clinical update and perspective

PubMed Central

Winograd, Evan K; Ciesielski, Michael J; Fenstermaker, Robert A

2016-01-01

Glioblastoma is the most common primary brain cancer. Aggressive treatment with surgery, radiation therapy and chemotherapy provides limited overall survival benefit. Glioblastomas have a formidable tumor microenvironment that is hostile to immunological effector cells and these cancers produce profound systemic immunosuppression. However, surgical resection of these tumors creates conditions that favor the use of immunotherapeutic strategies. Therefore, extensive surgical resection, when feasible, will remain part of the equation to provide an environment in which active specific immunotherapy has the greatest chance of working. Toward that end, a number of vaccination protocols are under investigation. Vaccines studied to date have produced cellular and humoral antitumor responses, but unequivocal clinical efficacy has yet to be demonstrated. In addition, focus is shifting toward the prospect of therapies involving vaccines in combination with immune checkpoint inhibitors and other immunomodulatory agents so that effector cells remain active against their targets systemically and within the tumor microenvironment. PMID:27993092

Death receptors as targets in cancer.

PubMed

Micheau, O; Shirley, S; Dufour, F

2013-08-01

Anti-tumour therapies based on the use pro-apoptotic receptor agonists, including TNF-related apoptosis-inducing ligand (TRAIL) or monoclonal antibodies targeting TRAIL-R1 or TRAIL-R2, have been disappointing so far, despite clear evidence of clinical activity and lack of adverse events for the vast majority of these compounds, whether combined or not with conventional or targeted anti-cancer therapies. This brief review aims at discussing the possible reasons for the lack of apparent success of these therapeutic approaches and at providing hints in order to rationally design optimal protocols based on our current understanding of TRAIL signalling regulation or resistance for future clinical trials. This article is part of a themed section on Emerging Therapeutic Aspects in Oncology. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2013.169.issue-8. © 2013 The British Pharmacological Society.

Oncolytic virus therapies.

PubMed

Buonaguro, Franco Maria; Tornesello, Maria Lina; Izzo, Francesco; Buonaguro, Luigi

2012-11-01

Oncolytic virus (OV) therapy currently represents one of the most promising approaches to cancer treatment for their dual anticancer mechanisms: direct lysis of cancer cells (oncolytic feature) and activation of the immunosystem (cancer vaccine aspect). The latter demonstrates the advantage of a multi-target approach against multiple tumor-associated antigens. Since the 2005 SFDA (the Chinese FDA) approval for the clinical use of Oncorine™, the first human OV-based cancer treatment, more than 200 patents have been filed worldwide and several Phase I/II studies have been conducted. This patent review analyzes patents and clinical studies of the most promising OV products to highlight the pros and cons of this innovative anticancer approach, which is currently being tested in several cancers (i.e., hepatocellular carcinoma, melanoma and glioblastoma) by systemic as well as intratumoral injection. Clinical results, although effective only for a limited period of time, are encouraging. Combined treatments with radio or chemotherapeutic protocols are also in progress.

Quantitative sensory testing of neuropathic pain patients: potential mechanistic and therapeutic implications.

PubMed

Pfau, Doreen B; Geber, Christian; Birklein, Frank; Treede, Rolf-Detlef

2012-06-01

Quantitative sensory testing (QST) is a widely accepted tool to investigate somatosensory changes in pain patients. Many different protocols have been developed in clinical pain research within recent years. In this review, we provide an overview of QST and tested neuroanatomical pathways, including peripheral and central structures. Based on research studies using animal and human surrogate models of neuropathic pain, possible underlying mechanisms of chronic pain are discussed. Clinically, QST may be useful for 1) the identification of subgroups of patients with different underlying pain mechanisms; 2) prediction of therapeutic outcomes; and 3) quantification of therapeutic interventions in pain therapy. Combined with sensory mapping, QST may provide useful information on the site of neural damage and on mechanisms of positive and negative somatosensory abnormalities. The use of QST in individual patients for diagnostic purposes leading to individualized therapy is an interesting concept, but needs further validation.

Sofalcone, a mucoprotective agent, increases the cure rate of Helicobacter pylori infection when combined with rabeprazole, amoxicillin and clarithromycin

PubMed Central

Isomoto, Hajime; Furusu, Hisashi; Ohnita, Ken; Wen, Chun-Yang; Inoue, Kenichiro; Kohno, Shigeru

2005-01-01

AIM: The mucoprotective agents, sofalcone and polaprezinc have anti-Helicobacter pylori (H pylori) activities. We determined the therapeutic effects of sofalcone and polaprezinc when combined with rabeprazole, amoxicillin and clarithromycin for Helicobacter pylori infection. METHODS: One hundred and sixty-five consecutive outpatients with peptic ulcer and H pylori infection were randomly assigned to one of the following three groups and medicated for 7 d. Group A: triple therapy with rabeprazole (10 mg twice daily), clarithromycin (200 mg twice daily) and amoxicillin (750 mg twice daily). Group B: sofalcone (100 mg thrice daily) plus the triple therapy. Group C: polaprezinc (150 mg twice daily) plus the triple therapy. Eradication was considered successful if 13C-urea breath test was negative at least 4 wk after cessation of eradication regimens or successive famotidine in the cases of active peptic ulcer. RESULTS: On intention-to-treat basis, H pylori cure was achieved in 43 of 55 (78.2%) patients, 47 of 54 (87.0%) and 45 of 56 (80.4%) for the groups A, B and C respectively. Using per protocol analysis, the eradication rates were 81.1% (43/53), 94.0% (47/50) and 84.9% (45/53) respectively. There was a significant difference in the cure rates between group A and B. Adverse events occurred in 10, 12 and 11 patients, from groups A, B and C respectively, but the events were generally mild. CONCLUSION: The addition of sofalcone, but not polaprezinc, significantly increased the cure rate of H pylori infection when combined with the rabeprazole-amoxicillin-clarithromycin regimen. PMID:15786539

Personalized Medicine in Allergic Asthma: At the Crossroads of Allergen Immunotherapy and "Biologicals".

PubMed

Fritzsching, Benedikt

2017-01-01

Major allergic disease can be viewed as clinical syndromes rather than discrete disease entities. Emerging evidence indicates that allergic asthma includes several disease phenotypes. Immunological deviation toward high T helper cell type 2 cytokine levels has been demonstrated for a subgroup of pediatric asthma patients, and now, several novel monoclonal antibodies have been approved for treatment of this subgroup as a stratified approach of "personalized" medicine in allergy. Introduction of component-based IgE testing before allergen immunotherapy (AIT), i.e., testing for IgE cross-reactivity before initiation of AIT, has also brought stratified medicine into allergy therapy. Improved responder criteria, which identify treatment-responders previous to therapy, might foster this stratification and even individualized AIT might have an impact for tailor-made therapy in the future. Furthermore, combining antibody-based treatment with AIT could help to establish more rapid AIT protocols even for allergens with a high risk of anaphylactic reactions. Efforts to advance such "personalized" medicine in pediatric allergy might be challenged by several issues including high costs for the health-care system, increasing complexity of allergy therapy, the need for physician allergy expertise, and furthermore ethical considerations and data safety issues.

Analysis of the clonal repertoire of gene-corrected cells in gene therapy.

PubMed

Paruzynski, Anna; Glimm, Hanno; Schmidt, Manfred; Kalle, Christof von

2012-01-01

Gene therapy-based clinical phase I/II studies using integrating retroviral vectors could successfully treat different monogenetic inherited diseases. However, with increased efficiency of this therapy, severe side effects occurred in various gene therapy trials. In all cases, integration of the vector close to or within a proto-oncogene contributed substantially to the development of the malignancies. Thus, the in-depth analysis of integration site patterns is of high importance to uncover potential clonal outgrowth and to assess the safety of gene transfer vectors and gene therapy protocols. The standard and nonrestrictive linear amplification-mediated PCR (nrLAM-PCR) in combination with high-throughput sequencing exhibits technologies that allow to comprehensively analyze the clonal repertoire of gene-corrected cells and to assess the safety of the used vector system at an early stage on the molecular level. It enables clarifying the biological consequences of the vector system on the fate of the transduced cell. Furthermore, the downstream performance of real-time PCR allows a quantitative estimation of the clonality of individual cells and their clonal progeny. Here, we present a guideline that should allow researchers to perform comprehensive integration site analysis in preclinical and clinical studies. Copyright © 2012 Elsevier Inc. All rights reserved.

A protocol proposition of cell therapy for the treatment of chronic obstructive pulmonary disease.

PubMed

Ribeiro-Paes, J T; Stessuk, T; Marcelino, M; Faria, C; Marinelli, T; Ribeiro-Paes, M J

2014-01-01

The main feature of pulmonary emphysema is airflow obstruction resulting from the destruction of the alveolar walls distal to the terminal bronchioles. Existing clinical approaches have improved and extended the quality of life of emphysema patients. However, no treatment currently exists that can change the disease course and cure the patient. The different therapeutic approaches that are available aim to increase survival and/or enhance the quality of life of emphysema patients. In this context, cell therapy is a promising therapeutic approach with great potential for degenerative pulmonary diseases. In this protocol proposition, all patients will be submitted to laboratory tests, such as evaluation of heart and lung function and routine examinations. Stem cells will be harvested by means of 10 punctures on each anterior iliac crest, collecting a total volume of 200mL bone marrow. After preparation, separation, counting and labeling (optional) of the mononuclear cells, the patients will receive an intravenous infusion from the pool of Bone Marrow Mononuclear Cells (BMMC). This article proposes a rational and safe clinical cellular therapy protocol which has the potential for developing new projects and can serve as a methodological reference for formulating clinical application protocols related to the use of cellular therapy in COPD. This study protocol was submitted and approved by the Brazilian National Committee of Ethics in Research (CONEP - Brazil) registration number 14764. It is also registered in ClinicalTrials.gov (NCT01110252). Copyright © 2013 Sociedade Portuguesa de Pneumologia. Published by Elsevier España. All rights reserved.

The "ComPAS Trial" combined treatment model for acute malnutrition: study protocol for the economic evaluation.

PubMed

Lelijveld, Natasha; Bailey, Jeanette; Mayberry, Amy; Trenouth, Lani; N'Diaye, Dieynaba S; Haghparast-Bidgoli, Hassan; Puett, Chloe

2018-04-24

Acute malnutrition is currently divided into severe (SAM) and moderate (MAM) based on level of wasting. SAM and MAM currently have separate treatment protocols and products, managed by separate international agencies. For SAM, the dose of treatment is allocated by the child's weight. A combined and simplified protocol for SAM and MAM, with a standardised dose of ready-to-use therapeutic food (RUTF), is being trialled for non-inferior recovery rates and may be more cost-effective than the current standard protocols for treating SAM and MAM. This is the protocol for the economic evaluation of the ComPAS trial, a cluster-randomised controlled, non-inferiority trial that compares a novel combined protocol for treating uncomplicated acute malnutrition compared to the current standard protocol in South Sudan and Kenya. We will calculate the total economic costs of both protocols from a societal perspective, using accounting data, interviews and survey questionnaires. The incremental cost of implementing the combined protocol will be estimated, and all costs and outcomes will be presented as a cost-consequence analysis. Incremental cost-effectiveness ratio will be calculated for primary and secondary outcome, if statistically significant. We hypothesise that implementing the combined protocol will be cost-effective due to streamlined logistics at clinic level, reduced length of treatment, especially for MAM, and reduced dosages of RUTF. The findings of this economic evaluation will be important for policymakers, especially given the hypothesised non-inferiority of the main health outcomes. The publication of this protocol aims to improve rigour of conduct and transparency of data collection and analysis. It is also intended to promote inclusion of economic evaluation in other nutrition intervention studies, especially for MAM, and improve comparability with other studies. ISRCTN 30393230 , date: 16/03/2017.

Combination therapy with carfilzomib, lenalidomide and dexamethasone (KRd) results in an unprecedented purity of the stem cell graft in newly diagnosed patients with myeloma.

PubMed

Tageja, Nishant; Korde, Neha; Kazandjian, Dickran; Panch, Sandhya; Manasanch, Elisabet; Bhutani, Manisha; Kwok, Mary; Mailankody, Sham; Yuan, Constance; Stetler-Stevenson, Maryalice; Leitman, Susan F; Sportes, Claude; Landgren, Ola

2018-05-04

Still, many physicians give 4 cycles of combination therapy to multiple myeloma patients prior to collection of stem cells for autologous bone marrow transplant. This tradition originates from older doxorubicin-containing regiments which limited the number of cycles due to cumulative cardiotoxicity. Using older regiments, most patients had residual myeloma cells in their autologous stem-cell grafts during collection. Emerging data show that newly diagnosed multiple myeloma patients treated with modern carfilzomib/lenalidomide/dexamethasone (KRd) therapy, on average, take 6 cycles until reaching minimal residual disease (MRD) negativity. We assessed newly diagnosed patients treated with KRd focusing MRD status both in the individual patient's bone marrow, and the corresponding autologous hematopoietic progenitor cell grafts during collection. Per protocol, stem-cell collection was allowed after 4 to 8 cycles of KRd. We found similar stem-cell yield independent of the number of cycles of KRd. At stem-cell collection, 11/30 patients (36.6%) were MRD negative in their bone marrow; all 11 patients had MRD negative hematopoietic progenitor cell grafts. Furthermore, 18/19 patients who were MRD positive in their bone marrows also had MRD negative hematopoietic progenitor cell grafts. These observations support 6 cycles of KRd as an efficacious and safe induction strategy prior to stem-cell collection.

Usefulness of Sodium Bicarbonate for the Prevention of Contrast-Induced Nephropathy in Patients Undergoing Cardiac Resynchronization Therapy.

PubMed

Alonso, Pau; Sanz, Jorge; García-Orts, Ana; Reina, Samuel; Jiménez, Sonia; Osca, Joaquín; Cano, Oscar; Andrés, Ana; Sancho-Tello, María José; Martínez, Luis

2017-11-01

The use of contrast media during cardiac resynchronization therapy (CRT) devices implantation is associated with the risk of contrast-induced nephropathy (CIN). The aim of this study was to evaluate the possible beneficial role of periprocedural intravenous volume expansion with isotonic saline and sodium bicarbonate solution in patients who undergo CRT implantation. Eligible patients were randomly assigned in a 1:1 ratio to receive hydration plus one-sixth molar sodium bicarbonate (study group) or not (control group). Primary end point was CIN incidence. Secondary end points were (1) a combined end point of death, heart transplantation, or hospitalization for heart failure at 12 months, (2) incidence of death, and (3) the need for renal replacement therapy at 12 months. Final analysis was performed with 93 patients. In the hydration group CIN incidence was significantly reduced related to control group (0% vs 11%, p = 0.02). There was a trend to reduce the combined end point in hydration group (12.5% vs 22%, p = 0.14). Finally, CIN incidence was related to a higher 12 months mortality (25% vs 7%, p = 0.03). In conclusion, CIN incidence was 11% in a nonselected population of patients receiving a CRT device. CIN appearance could be reduced by using a hydration protocol based on sodium bicarbonate and isotonic saline. Copyright © 2017 Elsevier Inc. All rights reserved.

Incorporation of aptamers in the terminal loop of shRNAs yields an effective and novel combinatorial targeting strategy.

PubMed

Pang, Ka Ming; Castanotto, Daniela; Li, Haitang; Scherer, Lisa; Rossi, John J

2018-01-09

Gene therapy by engineering patient's own blood cells to confer HIV resistance can potentially lead to a functional cure for AIDS. Toward this goal, we have previously developed an anti-HIV lentivirus vector that deploys a combination of shRNA, ribozyme and RNA decoy. To further improve this therapeutic vector against viral escape, we sought an additional reagent to target HIV integrase. Here, we report the development of a new strategy for selection and expression of aptamer for gene therapy. We developed a SELEX protocol (multi-tag SELEX) for selecting RNA aptamers against proteins with low solubility or stability, such as integrase. More importantly, we expressed these aptamers in vivo by incorporating them in the terminal loop of shRNAs. This novel strategy allowed efficient expression of the shRNA-aptamer fusions that targeted RNAs and proteins simultaneously. Expressed shRNA-aptamer fusions targeting HIV integrase or reverse transcriptase inhibited HIV replication in cell cultures. Viral inhibition was further enhanced by combining an anti-integrase aptamer with an anti-HIV Tat-Rev shRNA. This construct exhibited efficacy comparable to that of integrase inhibitor Raltegravir. Our strategy for the selection and expression of RNA aptamers can potentially extend to other gene therapy applications. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Cefepime and amikacin as empirical therapy in patients with febrile neutropaenia: a single-centre phase II prospective survey.

PubMed

Mebis, J; Vandeplassche, S; Goossens, H; Berneman, Z N

2009-01-01

The aim of the survey was to prospectively evaluate the effectiveness of the combination therapy cefepime and amikacin in the initial treatment of haematology patients with febrile neutropaenia. Two hundred twenty (220) episodes of febrile neutropaenia were analysed in 54 males and 82 females (median age 58 years), most patients had a severe neutropaenia with in 72% of all periods a neutrophil count of less than 100. Microbiological infection was confirmed in 72 cases (32.8%). Sixty-one (61) bacteria were isolated from blood cultures of which 22 were identified as Gram-negative bacteria and 38 as Gram-positive bacteria. Sixty-three (63) episodes (28.6%) were clinically documented, 85 episodes (38.6%) were fever of unknown origin. Clinical cure was achieved in 123 febrile episodes (56%) after initiation of the current antibiotic protocol; another 22 patients (10%) became afebrile after modifying the initial antibiotic regimen 48 hours or longer after treatment initiation. In 61 cases (27.7%) there was persistent fever or re-occurrence of fever, these cases were considered as treatment failure. Eight patients (3.6%) died during the study. This survey has demonstrated that the combination therapy with cefepime and amikacin can be considered as an effective treatment for febrile neutropaenia in high-risk haematological patients in our centre with a high incidence of resistance to Gram-negative bacteria.

COMBIT: protocol of a randomised comparison trial of COMbined modified constraint induced movement therapy and bimanual intensive training with distributed model of standard upper limb rehabilitation in children with congenital hemiplegia.

PubMed

Boyd, Roslyn N; Ziviani, Jenny; Sakzewski, Leanne; Miller, Laura; Bowden, Joanne; Cunnington, Ross; Ware, Robert; Guzzetta, Andrea; Al Macdonell, Richard; Jackson, Graeme D; Abbott, David F; Rose, Stephen

2013-06-28

Children with congenital hemiplegia often present with limitations in using their impaired upper limb which impacts on independence in activities of daily living, societal participation and quality of life. Traditional therapy has adopted a bimanual training approach (BIM) and more recently, modified constraint induced movement therapy (mCIMT) has emerged as a promising unimanual approach. Evidence of enhanced neuroplasticity following mCIMT suggests that the sequential application of mCIMT followed by bimanual training may optimise outcomes (Hybrid CIMT). It remains unclear whether more intensely delivered group based interventions (hCIMT) are superior to distributed models of individualised therapy. This study aims to determine the optimal density of upper limb training for children with congenital hemiplegia. A total of 50 children (25 in each group) with congenital hemiplegia will be recruited to participate in this randomized comparison trial. Children will be matched in pairs at baseline and randomly allocated to receive an intensive block group hybrid model of combined mCIMT followed by intensive bimanual training delivered in a day camp model (COMBiT; total dose 45 hours direct, 10 hours of indirect therapy), or a distributed model of standard occupational therapy and physiotherapy care (SC) over 12 weeks (total 45 hours direct and indirect therapy). Outcomes will be assessed at 13 weeks after commencement, and retention of effects tested at 26 weeks. The primary outcomes will be bimanual coordination and unimanual upper-limb capacity. Secondary outcomes will be participation and quality of life. Advanced brain imaging will assess neurovascular changes in response to treatment. Analysis will follow standard principles for RCTs, using two-group comparisons on all participants on an intention-to-treat basis. Comparisons will be between treatment groups using generalized linear models. ACTRN12613000181707.

[Simple parameters of antibiotic utilization and diagnostic background of antimicrobial therapy in Hungarian hospitals in 1995].

PubMed

Almási, I; Ternák, G

1997-02-23

This paper is published as second part of a survey on antibiotic utilisation of 8 Hungarian hospitals in January, 1995. The length of hospital stay of the patients receiving systemic antibiotic treatment was significantly higher (P < 0.0001) than those of not receiving such treatment. After exclusion of the patients suffering from nosocomial infections, average of the excess of hospital days was 4.65. Comparing the figures of patients receiving one or more antibiotic/one hospital stay and the rate of monotherapy and combined therapy and number of used antibiotics/100 discharged patients or/100 patients treated with antibiotics it was found that these indexes were most favourable in that hospital, where antibiotic policy was in function. Examining diagnoses (perioperative profilaxis 32.7%, pneumonia 13.3% of the 753 diagnoses) and drugs (metronidazol 26.3%, aminoglycosides 20% of the 1455 antibiotics) most frequently found in cases of combined antibiotic therapy it was concluded that parallel treatment with two or more antibiotic was often unjustified. Only 11% of antibiotics was used as directed against known bacteria. It was found that the rate of the achieved microbiological examinations and targeted therapy was low even if microbiological samples were easy to obtain. It was not the main purpose of the survey to get data of the clinical diagnostic background of antibiotic therapy, but indirect signs showed that these drugs were often used without sufficient clinical evidences (anamnesis, physical status, labor, X-ray and other tests) of infection. Authors recommend further survey in order to find out the causes of insufficiency of diagnoses. They also propose elaboration of diagnostic protocols.

Ablative fractional carbon dioxide laser combined with intense pulsed light for the treatment of photoaging skin in Chinese population: A split-face study.

PubMed

Mei, Xue-Ling; Wang, Li

2018-01-01

Intense pulsed light (IPL) is effective for the treatment of lentigines, telangiectasia, and generalized erythema, but is less effective in the removal of skin wrinkles. Fractional laser is effective on skin wrinkles and textural irregularities, but can induce postinflammatory hyperpigmentation (PIH), especially in Asians. This study evaluated the safety and efficacy of ablative fractional laser (AFL) in combination with IPL in the treatment of photoaging skin in Asians.This study included 28 Chinese women with Fitzpatrick skin type III and IV. The side of the face to be treated with IPL alone (3 times) or AFL in combination with IPL (2 IPL treatments and 1 AFL treatment) was randomly selected. Skin conditions including hydration, transepidermal water loss, elasticity, spots, ultraviolet spots, brown spots, wrinkle, texture, pore size and red areas, as well as adverse effects were evaluated before the treatment and at 30 days after the treatment.Compared with IPL treatment alone, AFL in combination with IPL significantly increased elasticity, decreased pore size, reduced skin wrinkles, and improved skin texture (P = .004, P = .039, P = .015, and P = .035, respectively). Both treatment protocols produced similar effects in relation to the improvement of photoaging-induced pigmentation. The combined therapy did not impair epidermal barrier function. No postoperative infection, hypopigmentation, or scarring occurred after IPL and AFL treatments. PIH occurred at 1 month after AFL treatment and disappeared at 30 days after completion of the combined therapy.AFL in combination with IPL is safe and effective for photoaging skin in Asians. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

An efficacious oral health care protocol for immunocompromised patients.

PubMed

Solomon, C S; Shaikh, A B; Arendorf, T M

1995-01-01

A twice-weekly oral and perioral examination was provided to 120 patients receiving antineoplastic therapy. Sixty patients were monitored while following the traditional hospital oral care protocol (chlorhexidine, hydrogen peroxide, sodium bicarbonate, thymol glycol, benzocaine mouthrinse, and nystatin). The mouth care protocol was then changed (experimental protocol = chlorhexidine, benzocaine lozenges, amphotericin B lozenges), and patients were monitored until the sample size matched that of the hospital mouth care regime. There was a statistically significant reduction in oral complications upon introduction and maintenance of the experimental protocol.

Protocolized fluid therapy in brain-dead donors: The multi-center randomized MOnIToR trial

PubMed Central

Al-Khafaji, Ali; Elder, Michele; Lebovitz, Daniel J; Murugan, Raghavan; Souter, Michael; Stuart, Susan; Wahed, Abdus S.; Keebler, Ben; Dils, Dorrie; Mitchell, Stephanie; Shutterly, Kurt; Wilkerson, Dawn; Pearse, Rupert; Kellum, John A

2015-01-01

BACKGROUND Critical shortages of organs for transplantation jeopardize many lives. Observational data suggest that better fluid management for deceased organ donors could increase organ recovery. We conducted the first large multi-center randomized trial in brain-dead donors to determine whether protocolized fluid therapy increases organs transplanted. METHODS We randomly assigned donors to either protocolized or usual care in eight organ procurement organizations. A “protocol-guided fluid therapy” algorithm targeting cardiac index, mean arterial pressure and pulse pressure variation was used. Our primary outcome was the number of organs transplanted per donor and our primary analysis was intention-to-treat. Secondary analyses included: 1) modified intention-to-treat where only subjects able to receive the intervention were included, and 2) twelve-month survival in transplant recipients. The study was stopped early. RESULTS We enrolled 556 donors; 279 protocolized care, 277 usual care. Groups had similar characteristics at baseline. The study protocol could be implemented in 76% of subjects randomized to the intervention. There was no significant difference in mean number of organs transplanted per donor: 3.39 organs per donor, (95%CI: 3.14-3.63) with protocolized care, compared to usual care 3.29 (95%CI: 3.04-3.54) (mean difference, 0.1, 95%CI: -0.25 to 0.45; p=0.56). In modified intention-to-treat analysis the mean number of organs increased (3.52 organs per donor, 95%CI: 3.23-3.8) but was not statistically significant (mean difference, 0.23, 95%CI: -0.15-0.61; p=0.23). Among the 1430 recipients of organs from study subjects, with data available, 56 deaths (7.8%) occurred in the protocolized care arm and 56 (7.9%) in the usual care arm in the first year (Hazard Ratio: 0.97, p=0.86). CONCLUSIONS In brain-dead organ donors, protocol-guided fluid therapy compared to usual care may not increase the number of organs transplanted per donor. PMID:25583616

Effect of live music therapy for patients undergoing magnetic resonance imaging.

PubMed

Walworth, Darcy D

2010-01-01

The purpose of the current study was to identify the effects of live music therapy interventions compared with preferred recorded music for patients undergoing MRI scans. To date, there has not been a published study involving the use of live music therapy during MRI scans. The current study investigated the differences between teenage through adult patients receiving live music therapy intervention during outpatient MRI scans versus the standard protocol of care listening to recorded music (N = 88). Subjects ranged in age from 15 to 93 years old. Results indicated subjects who received the live music therapy protocol reported significantly better perception of the MRI procedure (p < 0.05). Additionally, subjects receiving the live music therapy protocol had fewer scans repeated due to movement. Of the repeated images, 26% occurred in the live music group and 73% occurred in the recorded music group. Subjects receiving live music therapy also requested less breaks from the scan. Two percent of the live music subjects requested a break and 17.6% of the control patients requested breaks. When comparing the same type of scan between groups, subjects receiving the live music protocol required less time to complete the scans. For lumbar scans without contrast (N = 14, n = 7, n = 7), live music subjects spent an average of 4.63 less min per scan for a total of 32 less min for 7 subjects. For brain scans (N = 8, n = 4, n = 4), live music subjects spent an average of 5.8 less min per scan for a total of 23 less min for 4 subjects. Results of the current study supports the use of live music therapy intervention for teenage and adult patients undergoing MRI scans to reduce patient anxiety and improve patient perception of the scan experience. Additionally, live music therapy has the potential to shorten the length of time required for patients to complete MRI scans due to decreased patient movements and fewer breaks requested during the scans. The cost savings impact of reduced procedure time can positively impact the facility productivity by allowing more scans to be scheduled daily.

The efficacy of ranitidine bismuth citrate, amoxicillin and doxycycline or tetracycline regimens as a first line treatment for Helicobacter pylori eradication.

PubMed

Akyildiz, Murat; Akay, Sinan; Musoglu, Ahmet; Tuncyurek, Muge; Aydin, Ahmet

2009-01-01

The eradication rates of Helicobacter pylori (H. pylori) clearly decreased with standard PPI-based triple therapies. To assess the efficacy of two different triple therapies consisting of ranitidine bismuth citrate-amoxicillin-doxycycline and ranitidine bismuth citrate-amoxicillin-tetracycline combinations as a first line treatment option. One hundred and fifteen consecutive dyspeptic patients in whom H. pylori infection was diagnosed for the first time were enrolled in this study. The patients were randomized into two groups. Group 1 (n=57) was assigned to receive a 14-day triple therapy consisting of ranitidine bismuth citrate 400 mg (b.i.d.), amoxicillin 1 g (b.i.d) and doxycycline 100 mg (b.i.d.). Group 2 (n=58) was assigned to receive a 14-day triple therapy consisting of ranitidine bismuth citrate 400 mg (b.i.d.), amoxicillin 1 g (b.i.d.) and tetracycline 500 mg (q.i.d.). The eradication was achieved in 45.7% (21/46) and 40.8% (20/49) of the patients in group 1 and group 2, according to per protocol analysis. The intention-to-treat eradication rates were 36.8% (21/57) and 34.5% (20/58) in group 1 and group 2, respectively. Two-week therapy with neither ranitidine bismuth citrate-amoxicillin-doxycycline nor ranitidine bismuth citrate-amoxicillin-tetracycline is adequately effective for H. pylori eradication as a first line therapy.

Unpacking 'Artemisinin Resistance'.

PubMed

Wang, Jigang; Xu, Chengchao; Lun, Zhao-Rong; Meshnick, Steven R

2017-06-01

Artemisinin and its derivatives, in combination with partner drugs, are currently the most effective treatments for malaria parasite infection. Even though artemisinin has been widely used for decades, its mechanism of action had remained controversial until recently. Artemisinin combination therapies (ACTs) have recently been found to be losing efficacy in Southeast Asia. This 'artemisinin resistance', defined by a delayed parasite clearance time, has been associated with several genetic mutations. As with any other drug resistance phenotype, resistance can best be understood based on its mechanism of action. Recently, it was demonstrated that artemisinin attacks multiple parasitic targets, suggesting that mutations in drug targets are unlikely to cause high-level artemisinin resistance. These findings will help us to better understand the mechanisms of artemisinin resistance and suggest protocol modifications that may improve the efficacy of ACTs. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effect of low-level laser therapy (LLLT) and light-emitting diodes (LEDT) applied during combined training on performance and post-exercise recovery: protocol for a randomized placebo-controlled trial.

PubMed

Machado, Aryane Flauzino; Micheletti, Jéssica Kirsch; Vanderlei, Franciele Marques; Nakamura, Fabio Yuzo; Leal-Junior, Ernesto Cesar Pinto; Netto Junior, Jayme; Pastre, Carlos Marcelo

Previous studies have shown positive results of phototherapy for improving performance and accelerating recovery; however, the effects of phototherapy during training and after a primary adaptation remain unclear. The aim of this randomized controlled trial is to analyze the effects of phototherapy and combined training on clinical, functional, and psychological outcomes and on vascular endothelial growth factor. This randomized placebo-controlled trial by stratified sample will involve 45 healthy male participants. In phase 1, the participants will undergo six weeks of combined training (sprints and squats). In phase 2, participants will be allocated through stratified randomization (based on adaptation capacity) into three groups: active phototherapy group (AG), placebo group (PG), and non-treatment control group (CG). A new six-week training program will then start and the participants will receive the recovery strategy between sprints and squats. The primary outcome will be maximal isometric contraction. The secondary outcomes include strength and power testing, maximal incremental test, squat jump, sprint test, muscle soreness, pain threshold, perceptions of exertion and recovery, psychological questionnaire, and vascular endothelial growth factor. This will be the first trial to include phototherapy during training. We believe that this strategy will combine the ergogenic and prophylactic effects in the same session. Furthermore, an application protocol performed after primary adaptation may reflect the real effect of the technique. Copyright © 2017 Associação Brasileira de Pesquisa e Pós-Graduação em Fisioterapia. Publicado por Elsevier Editora Ltda. All rights reserved.

Effects of Guided Written Disclosure Protocol on mood states and psychological symptoms among parents of off-therapy acute lymphoblastic leukemia children.

PubMed

Martino, Maria Luisa; Freda, Maria Francesca; Camera, Flavia

2013-06-01

This study assesses the effects of Guided Written Disclosure Protocol on psychological distress in mothers and fathers of off-therapy acute lymphoblastic leukemia children. An experimental group participated in the writing intervention with a control group subject only to test-taking standards. The Symptom Questionnaire and Profile of Mood States were administered at baseline, post-intervention, and follow-up. Guided Written Disclosure Protocol had significant effects on the progressive reduction of anxiety, depression, somatic symptoms, hostility, tension-anxiety, and fatigue-inertia within the experimental group. However, the control group distress levels tended to worsen over time. The mediating role of emotional processing was highlighted.

Extravasation injuries: current medical and surgical treatment.

PubMed

Doornaert, M; Monstrey, S; Roche, N

2013-01-01

Extravasation is a devastating complication of intravenous therapy that develops when a drug infiltrates the interstitial tissue surrounding the vein. Due to the uncertain and possibly dramatic outcome, early recognition and adequate treatment with the aid of a standardized protocol are needed. A pubmed literature search was conducted and all relevant articles were reviewed for the development of an extravasation treatment protocol. An overview of current treatment guidelines and clinical experience is provided. The extravasation treatment protocol was implied during 1 year in this university hospital with satisfactory outcome. Treatment starts with prevention. In case of an established extravasation injury, early recognition, assessment of severity, and treatment with medical and/or surgical therapies are recommended.

Ultrasound-guided corticosteroid injection therapy for juvenile idiopathic arthritis: 12-year care experience.

PubMed

Young, Cody M; Shiels, William E; Coley, Brian D; Hogan, Mark J; Murakami, James W; Jones, Karla; Higgins, Gloria C; Rennebohm, Robert M

2012-12-01

Intra-articular corticosteroid injections are a safe and effective treatment for patients with juvenile idiopathic arthritis. The potential scope of care in ultrasound-guided corticosteroid therapy in children and a joint-based corticosteroid dose protocol designed to optimize interdisciplinary care are not found in the current literature. The purpose of this study was to report the spectrum of care, technique and safety of ultrasound-guided corticosteroid injection therapy in patients with juvenile idiopathic arthritis and to propose an age-weight-joint-based corticosteroid dose protocol. A retrospective analysis was performed of 198 patients (ages 21 months to 28 years) referred for treatment of juvenile idiopathic arthritis with corticosteroid therapy. Symptomatic joints and tendon sheaths were treated as prescribed by the referring rheumatologist. An age-weight-joint-based dose protocol was developed and utilized for corticosteroid dose prescription. A total of 1,444 corticosteroid injections (1,340 joints, 104 tendon sheaths) were performed under US guidance. Injection sites included small, medium and large appendicular skeletal joints (upper extremity 497, lower extremity 837) and six temporomandibular joints. For patients with recurrent symptoms, 414 repeat injections were performed, with an average time interval of 17.7 months (range, 0.5-101.5 months) between injections. Complications occurred in 2.6% of injections and included subcutaneous tissue atrophy, skin hypopigmentation, erythema and pruritis. US-guided corticosteroid injection therapy provides dynamic, precise and safe treatment of a broad spectrum of joints and tendon sheaths throughout the entire pediatric musculoskeletal system. An age-weight-joint-based corticosteroid dose protocol is effective and integral to interdisciplinary care of patients with juvenile idiopathic arthritis.

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

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.

Ketamine for the Acute Management of Excited Delirium and Agitation in the Prehospital Setting.

PubMed

Linder, Lauren M; Ross, Clint A; Weant, Kyle A

2018-01-01

Traditional first-line therapy in the prehospital setting for the acutely agitated patient includes an antipsychotic in combination with a benzodiazepine. Recently, interest has grown regarding the use of ketamine in the prehospital setting as an attempt to overcome the limitations of the traditional medications and provide a more safe and effective therapy. This review provides an overview of the pharmacology of ketamine, evaluates the literature regarding ketamine use for prehospital agitation, and proposes an algorithm that may be used within the prehospital setting. A literature review was conducted to identify articles utilizing ketamine in the prehospital setting. The review was limited to English-language articles identified in Embase (1988-June 2017) and the U.S. National Library of Medicine (1970-June 2017). References of all pertinent articles were also reviewed. Ten articles were identified including 418 patients receiving ketamine for agitation. The most commonly utilized route for administration was intramuscular (IM), with five of the seven IM administration studies using a ketamine dose of 5 mg/kg. Ketamine administered in this fashion was efficacious to achieve proper sedation during transport and did not require repeat dosing. Three studies applied a ketamine protocol to outline dosing and the management of ketamine adverse events. The most common adverse events identified were respiratory-related events and hypersalivation. Ketamine has a role for agitation management in the prehospital setting; however, emergency personnel education and ketamine protocols should be utilized to aid in safe and effective pharmacotherapy and provide guidance on the management of adverse events. Future prospective comparative studies, with protocolized standard ketamine regimens, are needed to further delineate the role of ketamine in agitation management and identify accurate adverse event incidence rates. © 2017 Pharmacotherapy Publications, Inc.

Effects of Arnica comp.-Heel® on reducing cardiovascular events in patients with stable coronary disease.

PubMed

Fioranelli, Massimo; Bianchi, Maria; Roccia, Maria G; Di Nardo, Veronica

2016-02-01

The purpose of the study was to evaluate the effectiveness of the treatment with one tablet a day of a low dose multicomponent medication (Arnica comp.-Heel® tablets) with anti-inflammatory properties in order to reduce the risk of cardiovascular events in patients with clinically stable coronary disease. The presence of inflammatory cells in atherosclerotic plaques of patients with stable coronary disease indicates the possibility to act by inhibiting the inflammatory phenomenon with Arnica comp.-Heel® tablets reducing the risk of instability of the plaque and, consequently, improving the clinical outcome in patients with stable coronary disease. Within this retrospective observational spontaneous clinical study 44 patients (31 males and 13 females) all presenting stable coronary artery disease were evaluated; 25 subjects were treated with only acetylsalicylic acid and/or clopidogrel in association with statins (standard therapeutic protocol) while for the other 18 subjects the standard therapeutic protocol was integrated with Arnica comp.-Heel® (one sublingual tablet/day). The primary outcome was to evaluate the incidence of acute coronary syndrome, out-of-hospital cardiac arrest, or non-cardioembolic ischemic stroke. The evaluation of the primary outcome showed that in the group of patients (18) who received the standard therapeutic protocol plus Arnica comp.-Heel® only one cardiovascular event was registered (5.6%) while in the group treated only with standard therapy 4 events were recorded in 25 patients (16%). The treatment with Arnica comp.-Heel® (one tablet/day) in combination with standard therapies for secondary prevention is effective in reducing the incidence of cardiovascular events in patients with stable coronary artery disease.

A major haemorrhage protocol improves the delivery of blood component therapy and reduces waste in trauma massive transfusion.

PubMed

Khan, Sirat; Allard, Shubha; Weaver, Anne; Barber, Colin; Davenport, Ross; Brohi, Karim

2013-05-01

Major haemorrhage protocols (MHP) are required as part of damage control resuscitation regimens in modern trauma care. The primary objectives of this study were to ascertain whether a MHP improved blood product administration and reduced waste compared to traditional massive transfusion protocols (MTP). Datasets on adult trauma admissions 1 year prior and 1 year post implementation of a MHP at a Level 1 trauma centre were obtained from the trauma registry. Demographic and clinical data were collected prospectively including mechanism of injury, physiological observations, ICU admission and length of stay. The volume of blood components (packed red blood cells, platelets, cryoprecipitate and fresh frozen plasma) issued, transfused, returned to stock and wasted within the first 24h was gathered retrospectively. Over the 2-year study period 2986 patient records were available for analysis. 40 patients required a 10+ Units of packed red blood ells transfusion in the MTP group vs. 56 patients post MHP implementation. The administration of blood component therapy improved significantly post MHP implementation. FFP:PRBC transfusion improved from 1:3 to 1:2 (p<0.01) and CRYO:PRBC improved from 1:10 to 1:7 (p<0.05). We reported a significant reduction in the waste of platelets from 14% to 2% (p<0.01). Outcomes had improved: Median hospital length of stay was reduced from 54 days to 26 days (p<0.05). Implementation of a MHP results in improved delivery of blood components and a reduction in the waste of blood products compared to the older model of MTP. In combination with educational programmes MHP can significantly improve blood product administration and patient outcomes in trauma haemorrhage. Level III diagnostic test study. Crown Copyright © 2012. Published by Elsevier Ltd. All rights reserved.

Is a controlled randomised trial the non-plus-ultra design? A contribution to discussion on comparative, controlled, non-randomised trials.

PubMed

Gaus, Wilhelm; Muche, Rainer

2013-05-01

Clinical studies provide formalised experience for evidence-based medicine (EBM). Many people consider a controlled randomised trial (CRT, identical to a randomised controlled trial RCT) to be the non-plus-ultra design. However, CRTs also have limitations. The problem is not randomisation itself but informed consent for randomisation and masking of therapies according to today's legal and ethical standards. We do not want to de-rate CRTs, but we would like to contribute to the discussion on clinical research methodology. Informed consent to a CRT and masking of therapies plainly select patients. The excellent internal validity of CRTs can be counterbalanced by poor external validity, because internal and external validity act as antagonists. In a CRT, patients may feel like guinea pigs, this can decrease compliance, cause protocol violations, reduce self-healing properties, suppress unspecific therapeutic effects and possibly even modify specific efficacy. A control group (comparative study) is most important for the degree of evidence achieved by a trial. Study control by detailed protocol and good clinical practice (controlled study) is second in importance and randomisation and masking is third (thus the sequence CRT instead of RCT). Controlled non-randomised trials are just as ambitious and detailed as CRTs. We recommend clinicians and biometricians to take high quality controlled non-randomised trials into consideration more often. They combine good internal and external validity, better suit daily medical practice, show better patient compliance and fewer protocol violations, deliver estimators unbiased by alienated patients, and perhaps provide a clearer explanation of the achieved success. Copyright © 2013 Elsevier Inc. All rights reserved.

Guidelines for the treatment of childhood-onset Graves' disease in Japan, 2016.

PubMed

Minamitani, Kanshi; Sato, Hirokazu; Ohye, Hidemi; Harada, Shohei; Arisaka, Osamu

2017-01-01

Purpose behind developing these guidelines: Over one decade ago, the "Guidelines for the Treatment of Graves' Disease with Antithyroid Drug, 2006" (Japan Thyroid Association (JTA)) were published as the standard drug therapy protocol for Graves' disease. The "Guidelines for the Treatment of Childhood-Onset Graves' Disease with Antithyroid Drug in Japan, 2008" were published to provide guidance on the treatment of pediatric patients. Based on new evidence, a revised version of the "Guidelines for the Treatment of Graves' Disease with Antithyroid Drug, 2006" (JTA) was published in 2011, combined with the "Handbook of Radioiodine Therapy for Graves' Disease 2007" (JTA). Subsequently, newer findings on pediatric Graves' disease have been reported. Propylthiouracil (PTU)-induced serious hepatopathy is an important problem in pediatric patients. The American Thyroid Association's guidelines suggest that, in principle, physicians must not administer PTU to children. On the other hand, the "Guidelines for the Treatment of Graves' Disease with Antithyroid Drug, 2011" (JTA) state that radioiodine therapy is no longer considered a "fundamental contraindication" in children. Therefore, the "Guidelines for the Treatment of Childhood-Onset Graves' Disease with Antithyroid Drug in Japan, 2008" required revision.

The emerging role of maxillofacial radiology in the diagnosis and management of patients with complex periodontitis.

PubMed

Scarfe, William C; Azevedo, Bruno; Pinheiro, Lucas R; Priaminiarti, Menik; Sales, Marcelo A O

2017-06-01

Contemporary periodontal therapy has evolved to become more interdisciplinary and increasingly involves more complex treatments, including bone and soft-tissue regenerative procedures. Therapeutic options require an imaging modality or combination of techniques that are capable of providing a diagnostic osseous baseline and facilitating quantification of smaller increments of bony change, both loss and additive, which are comparable over time. Intra-oral and panoramic radiography are the modalities most commonly used to identify the location, quantify the amount and the pattern of alveolar bone loss and determine response to therapy. Cone-beam computed tomography imaging offers specific advantages for periodontal diagnosis in that three-dimensional images of dental and alveolar bone structures can be rendered with accuracy. Cone-beam computed tomography has been shown to be clinically efficacious in demonstrating localized defects, such as furcation involvement and intrabony vertical and buccal/lingual defects, and in assessing the effects of regenerative therapy. In these situations, limited-field-of-view, high-resolution protocols are indicated. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Multicentre knowledge sharing and planning/dose audit on flattening filter free beams for SBRT lung

NASA Astrophysics Data System (ADS)

Hansen, C. R.; Sykes, J. R.; Barber, J.; West, K.; Bromley, R.; Szymura, K.; Fisher, S.; Sim, J.; Bailey, M.; Chrystal, D.; Deshpande, S.; Franji, I.; Nielsen, T. B.; Brink, C.; Thwaites, D. I.

2015-01-01

When implementing new technology into clinical practice, there will always be a need for large knowledge gain. The aim of this study was twofold, (I) audit the treatment planning and dose delivery of Flattening Filter Free (FFF) beam technology for Stereotactic Body Radiation Therapy (SBRT) of lung tumours across a range of treatment planning systems compared to the conventional Flatting Filter (FF) beams, (II) investigate how sharing knowledge between centres of different experience can improve plan quality. All vendor/treatment planning system (TPS) combinations investigated were able to produce acceptable treatment plans and the dose accuracy was clinically acceptable for all plans. By sharing knowledge between the different centres, the minor protocol violations (MPV) could be significantly reduced, from an average of 1.9 MPV per plan to 0.6 after such sharing of treatment planning knowledge. In particular, for the centres with less SBRT and/or volumetric- modulated arc therapy (VMAT) experience the MPV average per plan improved. All vendor/TPS combinations were also able to successfully deliver the FF and FFF SBRT VMAT plans. The plan quality and dose accuracy were found to be clinically acceptable.

Purified umbilical cord derived mesenchymal stem cell treatment in a case of systemic lupus erythematosus.

PubMed

Phillips, Christopher D; Wongsaisri, Pornpatcharin; Htut, Thein; Grossman, Terry

2017-12-01

Systemic lupus erythematosus (SLE) is a multiple organ system autoimmune disorder for which there is no known cure. We report a case of a young adult lady with SLE and Sjogren's with diagnostic and clinical resolution following purified umbilical cord derived mesenchymal stem cell (MSC) and globulin component protein macrophage activating factor (GcMAF) therapy in a combined multidisciplinary integrative medicine protocol. Our patient had complete reversal of all clinical and laboratory markers. We recommend a prospective randomized double blind study to assess the sustained efficacy of MSC and GcMAF in the treatment of autoimmune connective tissue diseases such as systemic lupus erythematosus.

Filter-Adapted Fluorescent In Situ Hybridization (FA-FISH) for Filtration-Enriched Circulating Tumor Cells.

PubMed

Oulhen, Marianne; Pailler, Emma; Faugeroux, Vincent; Farace, Françoise

2017-01-01

Circulating tumor cells (CTCs) may represent an easily accessible source of tumor material to assess genetic aberrations such as gene-rearrangements or gene-amplifications and screen cancer patients eligible for targeted therapies. As the number of CTCs is a critical parameter to identify such biomarkers, we developed fluorescent in situ hybridization (FISH) for CTCs enriched on filters (filter-adapted-FISH, FA-FISH). Here, we describe the FA-FISH protocol, the combination of immunofluorescent staining (DAPI/CD45) and FA-FISH techniques, as well as the semi-automated microscopy method that we developed to improve the feasibility and reliability of FISH analyses in filtration-enriched CTC.

Treatment of a Periodontic-Endodontic Lesion in a Patient with Aggressive Periodontitis.

PubMed

Fahmy, Mina D; Luepke, Paul G; Ibrahim, Mohamed S; Guentsch, Arndt

2016-01-01

Case Description. This case report describes the successful management of a left mandibular first molar with a combined periodontic-endodontic lesion in a 35-year-old Caucasian woman with aggressive periodontitis using a concerted approach including endodontic treatment, periodontal therapy, and a periodontal regenerative procedure using an enamel matrix derivate. In spite of anticipated poor prognosis, the tooth lesion healed. This case report also discusses the rationale behind different treatment interventions. Practical Implication. Periodontic-endodontic lesions can be successfully treated if dental professionals follow a concerted treatment protocol that integrates endodontic and periodontic specialties. General dentists can be the gatekeepers in managing these cases.

Treatment of a Periodontic-Endodontic Lesion in a Patient with Aggressive Periodontitis

PubMed Central

2016-01-01

Case Description. This case report describes the successful management of a left mandibular first molar with a combined periodontic-endodontic lesion in a 35-year-old Caucasian woman with aggressive periodontitis using a concerted approach including endodontic treatment, periodontal therapy, and a periodontal regenerative procedure using an enamel matrix derivate. In spite of anticipated poor prognosis, the tooth lesion healed. This case report also discusses the rationale behind different treatment interventions. Practical Implication. Periodontic-endodontic lesions can be successfully treated if dental professionals follow a concerted treatment protocol that integrates endodontic and periodontic specialties. General dentists can be the gatekeepers in managing these cases. PMID:27418983

Ventricular fractional shortening in 108 dogs with malignant lymphoma undergoing chemotherapy with a cyclic combination protocol including doxorubicin.

PubMed

Tater, G; Eberle, N; Hungerbuehler, S; Joetzke, A; Nolte, I; Wess, G; Betz, D

2012-01-01

The aim of this study was to evaluate whether changes in the left ventricular fractional shortening (LVFS) can be detected in dogs with malignant lymphoma undergoing a cyclic combination chemotherapy protocol including doxorubicin. Left ventricular fractional shortening as a stand-alone measurement will not show a significant change during the cyclic combination protocol. In this retrospective study, the records of dogs with malignant lymphoma treated between April 2001 and October 2010 were reviewed. Inclusion criteria comprised: a diagnosis of malignant lymphoma, a cyclic combination chemotherapy (including L-asparaginase, vincristine, cyclophosphamide, doxorubicin and prednisolone), and an echocardiographic examination by an experienced examiner before treatment and after each doxorubicin administration. One hundred and eight dogs were included and a total of 446 LVFS measurements had been performed. Patients were divided into four groups according to the number of doxorubicin administrations. Median LVFS did not change significantly during the cyclic combination protocol in all groups. All median LVFS values remained above the lower reference value of 25%. The measurement of LVFS did not show a significant change during the cyclic combination protocol treatment including doxorubicin in this population of dogs. Therefore either this cyclic combination protocol does not cause a systolic dysfunction or LVFS is not sensitive enough to detect early changes. Newer methods that are more sensitive then LVFS might be necessary to detect such changes.

Comparison of cyclophosphamide-thalidomide-dexamethasone to bortezomib-cyclophosphamide-dexamethasone as induction therapy for multiple myeloma patients in Brazil.

PubMed

Vigolo, Suelen; Zuckermann, Joice; Bittencourt, Rosane Isabel; Silla, Lúcia; Pilger, Diogo André

2017-09-01

Chemotherapy followed by autologous hematopoietic stem cell transplantation (HSCT) remains the standard treatment for multiple myeloma (MM). Thalidomide or bortezomib may be combined with cyclophosphamide and dexamethasone, in what are known as the CTD and VCD protocols, respectively. The objective of this study was to evaluate the clinical characteristics and response rates obtained with CTD and VCD, observing whether the inclusion of bortezomib to treat MM patients in Brazil increases therapeutic efficiency. Forty-three MM patients treated with induction protocols CTD and VCD between January 2010 and March 2015 were included. The parameters analyzed were staging, frequency of comorbidities prior to treatment, response rates obtained at each induction cycle, progression-free survival, and overall survival of patients. Very good partial response and complete response obtained with the VCD protocol were superior, compared with the CTD treatment. The presence of comorbidities was similar in the two groups, except kidney failure, which prevailed in the VCD group. Also, 78.3% and 48.3% of patients treated with the VCD and CTD protocols underwent autologous HSCT, respectively. In patients given the VCD protocol, 45.5% had complete response before autologous HSCT. Among those given CTD, this number was only 7.1% (p=0.023). Disease progression after autologous HSCT did not differ between the two groups. VCD afforded better responses than the CTD protocol, and improved patient condition before autologous HSCT. However, more studies are necessary including more patients and addressing various clinical conditions, besides the analysis of cost-effectiveness of these treatments. Copyright © 2017 King Faisal Specialist Hospital & Research Centre. Published by Elsevier B.V. All rights reserved.

Near "real" time magnetic resonance images as a monitoring system for interstitial laser therapy: experimental protocols

NASA Astrophysics Data System (ADS)

Castro, Dan J.; Farahani, Keyvan; Soudant, Jacques; Zwarun, Andrew A.; Lufkin, Robert B.

1992-06-01

The failure rate of cancer treatment remains unacceptably high, still being a leading cause of mortality in adults and children despite major advances over the past 50 years in the fields of surgery, radiation therapy and, more recently, chemo and immunotherapy. Surgical access to some deep tumors of the head and neck and other areas often require extensive dissections with residual functional and cosmetic deformities. Repeated treatment is not possible after maximum dose radiotherapy and chemotherapy is still limited by its systemic toxicity. An attractive solution to these problems would be the development of a new adjunctive method combining the best features of interstitial laser therapy for selective tumor destruction via minimally invasive techniques for access and 3-D magnetic resonance imaging (MRI) as a monitoring system for laser-tissue interactions. Interstitial laser therapy (ILT) via fiberoptics allow laser energy to be delivered directly into deeper tissues. However, this concept will become clinically useful only when noninvasive, accurate, and reproducible monitoring methods are developed to measure energy delivery to tissues. MRI has numerous advantages in evaluating the irreversible effects of laser treatment in tissues, since laser energy includes changes not only in the thermal motions of hydrogen protons within the tissue, but also in the distribution and mobility of water and lipids. These techniques should greatly improve the use of ILT in combination with MRI to allow treatment of deeper, more difficult to reach tumors of head and neck and other anatomical areas with a single needle stick.

A 96-well-plate-based optical method for the quantitative and qualitative evaluation of Pseudomonas aeruginosa biofilm formation and its application to susceptibility testing.

PubMed

Müsken, Mathias; Di Fiore, Stefano; Römling, Ute; Häussler, Susanne

2010-08-01

A major reason for bacterial persistence during chronic infections is the survival of bacteria within biofilm structures, which protect cells from environmental stresses, host immune responses and antimicrobial therapy. Thus, there is concern that laboratory methods developed to measure the antibiotic susceptibility of planktonic bacteria may not be relevant to chronic biofilm infections, and it has been suggested that alternative methods should test antibiotic susceptibility within a biofilm. In this paper, we describe a fast and reliable protocol for using 96-well microtiter plates for the formation of Pseudomonas aeruginosa biofilms; the method is easily adaptable for antimicrobial susceptibility testing. This method is based on bacterial viability staining in combination with automated confocal laser scanning microscopy. The procedure simplifies qualitative and quantitative evaluation of biofilms and has proven to be effective for standardized determination of antibiotic efficiency on P. aeruginosa biofilms. The protocol can be performed within approximately 60 h.

Spinal meningioma, aortic aneurysms and the missing link of observation: the anchoring heuristic approach.

PubMed

Floros, Nikolaos; Papadakis, Marios; Schelzig, Hubert; Oberhuber, Alexander

2018-03-10

Over the last three decades, the development of systematic and protocol-based algorithms, and advances in available diagnostic tests have become the indispensable parts of practising medicine. Naturally, despite the implementation of meticulous protocols involving diagnostic tests or even trials of empirical therapies, the cause of one's symptoms may still not be obvious. We herein report a case of chronic back pain, which took about 5 years to get accurately diagnosed. The case challenges the diagnostic assumptions and sets ground of discussion for the diagnostic reasoning pitfalls and heuristic biases that mislead the caring physicians and cost years of low quality of life to our patient. This case serves as an example of how anchoring heuristics can interfere in the diagnostic process of a complex and rare entity when combined with a concurrent potentially life-threatening condition. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Evolution of practice during the Interventional Management of Stroke III Trial and implications for ongoing trials.

PubMed

Broderick, Joseph P; Palesch, Yuko Y; Demchuk, Andrew M; Yeatts, Sharon D; Khatri, Pooja; Hill, Michael D; Jauch, Edward C; Jovin, Tudor G; Yan, Bernard; von Kummer, Rüdiger; Molina, Carlos A; Goyal, Mayank; Mazighi, Mikael; Schonewille, Wouter J; Engelter, Stefan T; Anderson, Craig; Spilker, Judith; Carrozzella, Janice; Janis, L Scott; Foster, Lydia D; Tomsick, Thomas A

2014-12-01

We explored changes in the patient population and practice of endovascular therapy during the course of the Interventional Management of Stroke (IMS) III Trial. Changes in baseline characteristics, use of baseline CT angiography, treatment times and specifics, and outcomes were compared between the first 4 protocols and the fifth and final protocol. Compared with subjects treated in the first 4 protocol versions (n=610), subjects treated in fifth and final protocol (n=46) were older (75 versus 68 years, P<0.0002) and less likely to have a pretreatment Rankin of 0 (76% versus 89%, P=0.01), were more likely to have a pretreatment CT angiography (65% versus 45%, P=0.009), had quicker median times in the endovascular arm from onset to start of intra-arterial therapy (209 versus 250 minutes, P=0.002) and to reperfusion (269 versus 344 minutes, P<0.0001), had a higher mean dose of total tissue-type plasminogen activator in the endovascular arm (74.0 versus 63.7 mg, P<0.0001), and were less likely to receive intra-arterial tissue-type plasminogen activator as part of the endovascular procedure (16% versus 44%, P=0.015). There were no significant differences in functional and safety outcomes between subjects treated in the 2 treatments arms in either the first 4 protocols or fifth protocol although the small sample size in the fifth protocol provided limited power. Endovascular technology and diagnostic approaches to acute stroke patients changed substantially during the IMS III Trial. Efforts to decrease the time to delivery of endovascular therapy were successful. © 2014 American Heart Association, Inc.

Combined Protocol for Acute Malnutrition Study (ComPAS) in rural South Sudan and urban Kenya: study protocol for a randomized controlled trial.

PubMed

Bailey, Jeanette; Lelijveld, Natasha; Marron, Bethany; Onyoo, Pamela; Ho, Lara S; Manary, Mark; Briend, André; Opondo, Charles; Kerac, Marko

2018-04-24

Acute malnutrition is a continuum condition, but severe and moderate forms are treated separately, with different protocols and therapeutic products, managed by separate United Nations agencies. The Combined Protocol for Acute Malnutrition Study (ComPAS) aims to simplify and unify the treatment of uncomplicated severe and moderate acute malnutrition (SAM and MAM) for children 6-59 months into one protocol in order to improve the global coverage, quality, continuity of care and cost-effectiveness of acute malnutrition treatment in resource-constrained settings. This study is a multi-site, cluster randomized non-inferiority trial with 12 clusters in Kenya and 12 clusters in South Sudan. Participants are 3600 children aged 6-59 months with uncomplicated acute malnutrition. This study will evaluate the impact of a simplified and combined protocol for the treatment of SAM and MAM compared to the standard protocol, which is the national treatment protocol in each country. We will assess recovery rate as a primary outcome and coverage, defaulting, death, length of stay, average weekly weight gain and average weekly mid-upper arm circumference (MUAC) gain as secondary outcomes. Recovery rate is defined across both treatment arms as MUAC ≥125 mm and no oedema for two consecutive visits. Per-protocol and intention-to-treat analyses will be conducted. If the combined protocol is shown to be non-inferior to the standard protocol, updating guidelines to use the combined protocol would eliminate the need for separate products, resources and procedures for MAM treatment. This would likely be more cost-effective, increase availability of services, enable earlier case finding and treatment before deterioration of MAM into SAM, promote better continuity of care and improve community perceptions of the programme. ISRCTN, ISRCTN30393230 . Registered on 16 March 2017.

Dosimetry applications in GATE Monte Carlo toolkit.

PubMed

Papadimitroulas, Panagiotis

2017-09-01

Monte Carlo (MC) simulations are a well-established method for studying physical processes in medical physics. The purpose of this review is to present GATE dosimetry applications on diagnostic and therapeutic simulated protocols. There is a significant need for accurate quantification of the absorbed dose in several specific applications such as preclinical and pediatric studies. GATE is an open-source MC toolkit for simulating imaging, radiotherapy (RT) and dosimetry applications in a user-friendly environment, which is well validated and widely accepted by the scientific community. In RT applications, during treatment planning, it is essential to accurately assess the deposited energy and the absorbed dose per tissue/organ of interest, as well as the local statistical uncertainty. Several types of realistic dosimetric applications are described including: molecular imaging, radio-immunotherapy, radiotherapy and brachytherapy. GATE has been efficiently used in several applications, such as Dose Point Kernels, S-values, Brachytherapy parameters, and has been compared against various MC codes which are considered as standard tools for decades. Furthermore, the presented studies show reliable modeling of particle beams when comparing experimental with simulated data. Examples of different dosimetric protocols are reported for individualized dosimetry and simulations combining imaging and therapy dose monitoring, with the use of modern computational phantoms. Personalization of medical protocols can be achieved by combining GATE MC simulations with anthropomorphic computational models and clinical anatomical data. This is a review study, covering several dosimetric applications of GATE, and the different tools used for modeling realistic clinical acquisitions with accurate dose assessment. Copyright © 2017 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

Practice guidelines for music interventions with hospitalized pediatric patients.

PubMed

Stouffer, Janice W; Shirk, Beverly J; Polomano, Rosemary C

2007-12-01

Music therapy is an effective complementary approach that can achieve specific therapeutic outcomes in the clinical management of pediatric patients. Growing research on music interventions has generated scientific knowledge about how this modality benefits patients and has formed the basis for effective protocols that can be used in practice. Although it can be challenging to translate research-based protocols into routine clinical care at the bedside, it is essential that music therapy interventions be aligned with evidence-based information and that accepted standards be established by the music therapy discipline to achieve the greatest benefit. The importance of partnerships between nurses and music therapists is emphasized to enhance the success of music-based treatments. This discussion synthesizes research findings that can be used to design pediatric practice guidelines in the application of music therapy.

Benefits of immediate EMDR vs. eclectic therapy intervention for victims of physical violence and accidents at the workplace: a pilot study.

PubMed

Brennstuhl, Marie-Jo; Tarquinio, Cyril; Strub, Lionel; Montel, Sebastien; Rydberg, Jenny Ann; Kapoula, Zoi

2013-06-01

This study focuses on 34 victims of aggression at the workplace, less than 48 hours following the incident of aggression. We compared victims who received an EMDR emergency protocol (URG-EMDR; n = 19) that we developed with those who received a method of intervention called eclectic therapy (n = 15). The results show that URG-EMDR therapy, provided within 48 hours, resulted in a greater decrease in perceived stress and a lower PCL-S score than eclectic therapy did. The scores were lower in both groups after 24 hours, and after 3 months, the drop was significantly greater among the victims treated with the URG-EMDR protocol; none of the EMDR-treated patients exhibited symptoms of posttraumatic stress.

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

Mammalian cells loaded with platinum-containing molecules are sensitized to fast atomic ions.

PubMed

Usami, N; Furusawa, Y; Kobayashi, K; Lacombe, S; Reynaud-Angelin, A; Sage, E; Wu, Ting-Di; Croisy, A; Guerquin-Kern, J-L; Le Sech, C

2008-07-01

This work investigates whether a synergy in cell death induction exists in combining atomic ions irradiation and addition of platinum salts. Such a synergy could be of interest in view of new cancer therapy protocol based on atomic ions--hadrontherapy--with the addition of radiosensitizing agents containing high-Z atoms. The experiment consists in irradiating by fast ions cultured cells previously exposed to dichloroterpyridine Platinum (PtTC) and analyzing cell survival by a colony-forming assay. Chinese Hamster Ovary (CHO) cells were incubated for six hours in medium containing 350 microM PtTC, and then irradiated by fast ions C(6+) and He(2+), with Linear Energy Transfer (LET) within range 2-70 keV/microm. In some experiments, dimethyl sulfoxide (DMSO) was added to investigate the role of free radicals. The intracellular localization of platinum was determined by Nano Secondary Ion Mass Spectroscopy (Nano-SIMS). For all LET examined, cell death rate is largely enhanced when irradiating in presence of PtTC. At fixed irradiation dose, cell death rate increases with increasing LET, while the platinum relative effect is larger at low LET. This finding suggests that hadrontherapy or protontherapy therapeutic index could be improved by combining irradiation procedure with concomitant chemotherapy protocols using platinum salts.

Errors in fluid therapy in medical wards.

PubMed

Mousavi, Maryam; Khalili, Hossein; Dashti-Khavidaki, Simin

2012-04-01

Intravenous fluid therapy remains an essential part of patients' care during hospitalization. There are only few studies that focused on fluid therapy in the hospitalized patients, and there is not any consensus statement about fluid therapy in patients who are hospitalized in medical wards. The aim of the present study was to assess intravenous fluid therapy status and related errors in the patients during the course of hospitalization in the infectious diseases wards of a referral teaching hospital. This study was conducted in the infectious diseases wards of Imam Khomeini Complex Hospital, Tehran, Iran. During a retrospective study, data related to intravenous fluid therapy were collected by two clinical pharmacists of infectious diseases from 2008 to 2010. Intravenous fluid therapy information including indication, type, volume and rate of fluid administration was recorded for each patient. An internal protocol for intravenous fluid therapy was designed based on literature review and available recommendations. The data related to patients' fluid therapy were compared with this protocol. The fluid therapy was considered appropriate if it was compatible with the protocol regarding indication of intravenous fluid therapy, type, electrolyte content and rate of fluid administration. Any mistake in the selection of fluid type, content, volume and rate of administration was considered as intravenous fluid therapy errors. Five hundred and ninety-six of medication errors were detected during the study period in the patients. Overall rate of fluid therapy errors was 1.3 numbers per patient during hospitalization. Errors in the rate of fluid administration (29.8%), incorrect fluid volume calculation (26.5%) and incorrect type of fluid selection (24.6%) were the most common types of errors. The patients' male sex, old age, baseline renal diseases, diabetes co-morbidity, and hospitalization due to endocarditis, HIV infection and sepsis are predisposing factors for the occurrence of fluid therapy errors in the patients. Our result showed that intravenous fluid therapy errors occurred commonly in the hospitalized patients especially in the medical wards. Improvement in knowledge and attention of health-care workers about these errors are essential for preventing of medication errors in aspect of fluid therapy.

Vital pulp therapy with bipolar electrocoagulation after intentional pulp exposure of fixed prosthodontic abutments: a clinical report.

PubMed

Livaditis, G J

2001-10-01

A clinical protocol is described for the treatment of intentional and unavoidable exposed pulps during crown preparation. The protocol includes a definitive cavity preparation to create space in the exposed dentin for an adhesive pulp barrier; procedures to develop the highly desirable hybrid zone to prevent microleakage; the use of a specific resinous material that serves as a long-term pulp barrier with a relatively neutral and biocompatible impact on the pulp; and the use of precise bipolar electrocoagulation to provide durable hemostasis for restoration of the pulp wall and a relatively clot-free surgical wound to facilitate healing. The protocol involves the application of gentle surgical and restorative procedures to support the inherent healing process to restore the health of the pulp. The patient presented was part of a larger investigation and was selected in an attempt to identify a fixed prosthodontic application of the proposed pulp therapy protocol.

Clinical, epidemiological, and therapeutic profile of dermatophytosis*

PubMed Central

Pires, Carla Andréa Avelar; da Cruz, Natasha Ferreira Santos; Lobato, Amanda Monteiro; de Sousa, Priscila Oliveira; Carneiro, Francisca Regina Oliveira; Mendes, Alena Margareth Darwich

2014-01-01

BACKGROUND The cutaneous mycoses, mainly caused by dermatophyte fungi, are among the most common fungal infections worldwide. It is estimated that 10% to 15% of the population will be infected by a dermatophyte at some point in their lives, thus making this a group of diseases with great public health importance. OBJECTIVE To analyze the clinical, epidemiological, and therapeutic profile of dermatophytosis in patients enrolled at the Dermatology service of Universidade do Estado do Pará, Brazil, from July 2010 to September 2012. METHOD A total of 145 medical records of patients diagnosed with dermatophytosis were surveyed. Data were collected and subsequently recorded according to a protocol developed by the researchers. This protocol consisted of information regarding epidemiological and clinical aspects of the disease and the therapy employed. RESULTS The main clinical form of dermatophyte infection was onychomycosis, followed by tinea corporis, tinea pedis, and tinea capitis. Furthermore, the female population and the age group of 51 to 60 years were the most affected. Regarding therapy, there was a preference for treatments that combine topical and systemic drugs, and the most widely used drugs were fluconazole (systemic) and ciclopirox olamine (topical). CONCLUSION This study showed the importance of recurrent analysis of the epidemiological profile of dermatophytosis to enable correct therapeutic and preventive management of these conditions, which have significant clinical consequences, with chronic, difficult-totreat lesions that can decrease patient quality of life and cause disfigurement. PMID:24770502

The impact of perioperative fluid therapy on short-term outcomes and 5-year survival among patients undergoing colorectal cancer surgery - A prospective cohort study within an ERAS protocol.

PubMed

Asklid, D; Segelman, J; Gedda, C; Hjern, F; Pekkari, K; Gustafsson, U O

2017-08-01

Restricted perioperative fluid therapy is one of several interventions in the enhanced recovery after surgery (ERAS) protocol, designed to reduce morbidity and hospital stay after surgery. The impact of this single intervention on short and long term outcome after colorectal surgery is unknown. This cohort study includes all consecutive patients operated with abdominal resection of colorectal cancer 2002-2007 at Ersta Hospital, Stockholm, Sweden. All patients were treated within an ERAS protocol and registered in the ERAS-database. Compliance to interventions in the ERAS protocol was analysed. The impact of a restrictive perioperative fluid therapy (≤3000 ml on the day of surgery) protocol on short-term outcomes as well as 5-year survival was assessed with multivariable analysis adjusted for confounding factors. Nine hundred and eleven patients were included. Patients receiving ≤3000 ml of intravenous fluids on the day of surgery had a lower risk of complications OR 0.44 (95% C I 0.28-0.71), symptoms delaying discharge OR 0.47(95% C I 0.32-0.70) and shorter length of stay compared with patients receiving >3000 ml. In cox regression analysis, the risk of cancer specific death was reduced with 55% HR 0.45(95% C I 0.25-0.81) for patients receiving ≤ 3000 ml compared with patients receiving >3000 ml. A restrictive compared with a non-restrictive perioperative fluid therapy on the day of surgery may be associated with lower short-term complication rates, faster recovery, shorter length of stay and improved 5-year survival. Copyright © 2017 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

Results of a Phase II Study to Evaluate the Efficacy of Docetaxel and Carboplatin in Metastatic Malignant Melanoma Patients Who Failed First-Line Therapy Containing Dacarbazine.

PubMed

Lee, Choong-kun; Jung, Minkyu; Choi, Hye Jin; Kim, Hye Ryun; Kim, Hyo Song; Roh, Mi Ryung; Ahn, Joong Bae; Chung, Hyun Cheol; Heo, Su Jin; Rha, Sun Young; Shin, Sang Joon

2015-10-01

There is no standard second-line regimen for malignant melanoma patients with disease progression after first-line chemotherapy, and platinum-alkylating agents combined with paclitaxel have shown modest efficacy. We conducted a phase II, open-label, single-arm study to test the efficacy of docetaxel combined with carboplatin for malignant melanoma patients who failed previous treatment with dacarbazine. Intravenous docetaxel (35 mg/m(2) on days 1 and 8 of each cycle) and carboplatin (area under the curve 3 on days 1 and 8 of each cycle) was administered every 21 days. Primary end point was objective response rate (ORR). Thirty patients were enrolled in the study, and the median follow-up duration was 19.8 months. Among 25 per-protocol patients, there were three responders (1 with complete response and 2 with partial response) and 17 stable disease patients (ORR, 12.0%). Among the per-protocol population, the median progression-free survival (PFS) was 4.3 months and the median overall survival (OS) was 9.6 months. Uveal melanoma patients (n=9) showed the best prognosis compared to other subtypes (median PFS, 7.6 months; OS, 9.9 months). The most common grade 3 or 4 adverse event was neutropenia (n=15, 50.0%). Docetaxel combined with carboplatin showed association with an acceptable safety profile and overall efficacy for patients with malignant melanoma who had progressed on chemotherapy containing dacarbazine.

Vaccine Therapy Plus Biological Therapy in Treating Adults With Metastatic Solid Tumors

ClinicalTrials.gov

2013-06-19

Colorectal Cancer; Endometrial Cancer; Head and Neck Cancer; Liver Cancer; Lung Cancer; Melanoma (Skin); Pancreatic Cancer; Testicular Germ Cell Tumor; Unspecified Adult Solid Tumor, Protocol Specific

Live cumulative network meta-analysis: protocol for second-line treatments in advanced non-small-cell lung cancer with wild-type or unknown status for epidermal growth factor receptor.

PubMed

Créquit, Perrine; Trinquart, Ludovic; Ravaud, Philippe

2016-08-03

Many second-line treatments for advanced non-small-cell lung cancer (NSCLC) have been assessed in randomised controlled trials, but which treatments work the best remains unclear. Novel treatments are being rapidly developed. We need a comprehensive up-to-date evidence synthesis of all these treatments. We present the protocol for a live cumulative network meta-analysis (NMA) to address this need. We will consider trials of second-line treatments in patients with advanced NSCLC with wild-type or unknown epidermal growth factor receptor status. We will consider any single agent of cytotoxic chemotherapy, targeted therapy, combination of cytotoxic chemotherapy and targeted therapy and any combination of targeted therapies. The primary outcomes will be overall survival and progression-free survival. The live cumulative NMA will be initiated with a NMA and then iterations will be repeated at regular intervals to keep the NMA up-to-date over time. We have defined the update frequency as 4 months, based on an assessment of the pace of evidence production on this topic. Each iteration will consist of six methodological steps: adaptive search for treatments and trials, screening of reports and selection of trials, data extraction, assessment of risk of bias, update of the network of trials and synthesis, and dissemination. We will set up a research community in lung cancer, with different groups of contributors of different skills. We will distribute tasks through online crowdsourcing. This proof-of-concept study in second-line treatments of advanced NSCLC will allow one for assessing the feasibility of live cumulative NMA and opening the path for this new form of synthesis. Ethical approval is not required because our study will not include confidential participant data and interventions. The description of all the steps and the results of this live cumulative NMA will be available online. CRD42015017592. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Photodynamic Synergistic Effect of Pheophorbide a and Doxorubicin in Combined Treatment against Tumoral Cells.

PubMed

Ruiz-González, Rubén; Milán, Paula; Bresolí-Obach, Roger; Stockert, Juan Carlos; Villanueva, Angeles; Cañete, Magdalena; Nonell, Santi

2017-02-17

A combination of therapies to treat cancer malignancies is at the forefront of research with the aim to reduce drug doses (ultimately side effects) and diminish the possibility of resistance emergence given the multitarget strategy. With this goal in mind, in the present study, we report the combination between the chemotherapeutic drug doxorubicin (DOXO) and the photosensitizing agent pheophorbide a (PhA) to inactivate HeLa cells. Photophysical studies revealed that DOXO can quench the excited states of PhA, detracting from its photosensitizing ability. DOXO can itself photosensitize the production of singlet oxygen; however, this is largely suppressed when bound to DNA. Photodynamic treatments of cells incubated with DOXO and PhA led to different outcomes depending on the concentrations and administration protocols, ranging from antagonistic to synergic for the same concentrations. Taken together, the results indicate that an appropriate combination of DOXO with PhA and red light may produce improved cytotoxicity with a smaller dose of the chemotherapeutic drug, as a result of the different subcellular localization, targets and mode of action of the two agents.

Photodynamic Synergistic Effect of Pheophorbide a and Doxorubicin in Combined Treatment against Tumoral Cells

PubMed Central

Ruiz-González, Rubén; Milán, Paula; Bresolí-Obach, Roger; Stockert, Juan Carlos; Villanueva, Angeles; Cañete, Magdalena; Nonell, Santi

2017-01-01

A combination of therapies to treat cancer malignancies is at the forefront of research with the aim to reduce drug doses (ultimately side effects) and diminish the possibility of resistance emergence given the multitarget strategy. With this goal in mind, in the present study, we report the combination between the chemotherapeutic drug doxorubicin (DOXO) and the photosensitizing agent pheophorbide a (PhA) to inactivate HeLa cells. Photophysical studies revealed that DOXO can quench the excited states of PhA, detracting from its photosensitizing ability. DOXO can itself photosensitize the production of singlet oxygen; however, this is largely suppressed when bound to DNA. Photodynamic treatments of cells incubated with DOXO and PhA led to different outcomes depending on the concentrations and administration protocols, ranging from antagonistic to synergic for the same concentrations. Taken together, the results indicate that an appropriate combination of DOXO with PhA and red light may produce improved cytotoxicity with a smaller dose of the chemotherapeutic drug, as a result of the different subcellular localization, targets and mode of action of the two agents. PMID:28218672

Exercise therapy for treatment of supraspinatus tears does not alter glenohumeral kinematics during internal/external rotation with the arm at the side.

PubMed

Ferrer, Gerald A; Miller, R Matthew; Zlotnicki, Jason P; Tashman, Scott; Irrgang, James J; Musahl, Volker; Debski, Richard E

2018-01-01

Rotator cuff tears are a significant clinical problem, with exercise therapy being a common treatment option for patients. Failure rates of exercise therapy may be due to the failure to improve glenohumeral kinematics. Tears involving the supraspinatus may result in altered glenohumeral kinematics and joint instability for internal/external rotation with the arm at the side because not all muscles used to stabilize the glenohumeral joint are functioning normally. The objective of the study is to assess in vivo glenohumeral kinematic changes for internal/external rotation motions with the arm at the side of patients with a symptomatic full-thickness supraspinatus tear before and after a 12-week exercise therapy programme. Five patients underwent dynamic stereoradiography analysis before and after a 12-week exercise therapy protocol to measure changes in glenohumeral kinematics during transverse plane internal/external rotation with the arm at the side. Patient-reported outcomes and shoulder strength were also evaluated. No patient sought surgery immediately following exercise therapy. Significant improvements in isometric shoulder strength and patient-reported outcomes were observed (p < 0.05). No significant changes in glenohumeral kinematics following physical therapy were found. Isolated supraspinatus tears resulted in increased joint translations compared to healthy controls from the previous literature for internal/external rotation with the arm at the side. Despite satisfactory clinical outcomes following exercise therapy, glenohumeral kinematics did not change. The lack of changes may be due to the motion studied or the focus of current exercise therapy protocols being increasing shoulder strength and restoring range of motion. Current exercise therapy protocols should be adapted to also focus on restoring glenohumeral kinematics to improve joint stability since exercise therapy may have different effects depending on the motions of daily living. Prognostic study, Level II.

10 CFR 35.657 - Therapy-related computer systems.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 10 Energy 1 2012-01-01 2012-01-01 false Therapy-related computer systems. 35.657 Section 35.657... Units, Teletherapy Units, and Gamma Stereotactic Radiosurgery Units § 35.657 Therapy-related computer... computer systems in accordance with published protocols accepted by nationally recognized bodies. At a...

10 CFR 35.657 - Therapy-related computer systems.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 10 Energy 1 2013-01-01 2013-01-01 false Therapy-related computer systems. 35.657 Section 35.657... Units, Teletherapy Units, and Gamma Stereotactic Radiosurgery Units § 35.657 Therapy-related computer... computer systems in accordance with published protocols accepted by nationally recognized bodies. At a...

10 CFR 35.657 - Therapy-related computer systems.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 10 Energy 1 2014-01-01 2014-01-01 false Therapy-related computer systems. 35.657 Section 35.657... Units, Teletherapy Units, and Gamma Stereotactic Radiosurgery Units § 35.657 Therapy-related computer... computer systems in accordance with published protocols accepted by nationally recognized bodies. At a...

10 CFR 35.657 - Therapy-related computer systems.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 1 2011-01-01 2011-01-01 false Therapy-related computer systems. 35.657 Section 35.657... Units, Teletherapy Units, and Gamma Stereotactic Radiosurgery Units § 35.657 Therapy-related computer... computer systems in accordance with published protocols accepted by nationally recognized bodies. At a...

10 CFR 35.657 - Therapy-related computer systems.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 1 2010-01-01 2010-01-01 false Therapy-related computer systems. 35.657 Section 35.657... Units, Teletherapy Units, and Gamma Stereotactic Radiosurgery Units § 35.657 Therapy-related computer... computer systems in accordance with published protocols accepted by nationally recognized bodies. At a...

The additional diagnostic value of a single-session combined scintigraphic and ultrasonographic examination in patients with thyroid and parathyroid diseases.

PubMed

Gedik, G K; Bozkurt, F M; Ugur, O; Grassetto, G; Rubello, D

2008-09-01

The aim of this study was to investigate the diagnostic efficacy and the clinical impact of scintigraphy combined with ultrasonography (USG) in the management of thyroid and parathyroid disorders in a large series of patients. A total of 387 consecutive patients referred to the Nuclear Medicine Department of Hacettepe University in the period from January to September 2007 for investigating a thyroid (N. 339 patients: 232 females and 107 males, mean age+/-SD=48.9+/-13.6 years) or a parathyroid disease (N. 48 patients: 34 females and 14 males, mean age+/-SD=47.4+/-9.6 years) were prospectively evaluated, systematically performing both scintigraphy and USG in a single-day session. All the examinations were independently reviewed by two nuclear medicine physicians; in cases of discrepancy (3%) a final diagnosis was reached by consensus. For thyroid pathologies, USG results were considered to provide additional diagnostic information over scintigraphy: 1) if more nodules were identified; 2) if an irregular hyperactive area at scintigraphy suspicious for the presence of a nodule was clearly characterized at USG; 3) if a nodule missed at scintigraphy because of small size (<1 cm) was well depicted at USG, thus allowing an USG-guided fine needle aspiration cytology (FNAC) to reach a final diagnosis. For parathyroid pathologies, USG was considered to provide additional diagnostic information over scintigraphy if a low intensity radiotracer retention from the parathyroid suspected of being a parathyroid enlargement was clearly depicted at USG. In thyroid diseases, scintigraphy was considered to provide additional diagnostic information over USG, if the functional status of a diffuse or uni- or multi-nodular goiter were clearly defined at scintigraphy. In parathyroid diseases, scintigraphy was considered to provide additional diagnostic information over USG, if the differential diagnosis between a lymph node or a muscle or a vessel depicted at USG was clearly defined as a parathyroid enlargement at scintigraphy. Lastly, the clinical impact of the single-day combined scintigraphic/USG protocol was evaluated. USG. In the thyroid diseases group, USG was particularly useful: 1) to detect additional nodules in glands with suppressed thyroid tissue; 2) to disclose small thyroid nodules (<1 cm) in which it was possible to perform a USG-FNAC. In the parathyroid diseases group, USG was particularly useful for the detection of parathyroid enlargements not visualized at scintigraphy because characterized by a rapid wash-out of the radiotracer and thus by a low radioactivity intensity in the delayed scintigraphic images. Scintigraphy. In the thyroid diseases group, scintigraphy was particularly useful: 1) to diagnose a diffuse hyperfunctioning thyroid gland, and to differentiate in multinodular goiters the hyper- from the hypo-functioning nodules. In the hyperparathyroid diseases group, scintigraphy was particular useful in making a differential diagnosis between a true parathyroid enlargement vs. a lymph node or a muscle or a vessel as depicted at USG, and in cases with deeply or ectopically-positioned parathyroid glands. Combined imaging approach. Combined interpretation provided additional benefit in 225 of 339 patients (64.4%). Overall, using the combined scintigraphic/USG single-day protocol, in the thyroid diseases group the therapeutic strategy (drug therapy vs radioiodine therapy vs surgery) was changed in 176/225 patients (78.2%, P<0.001 by chi(2) of Pearson), and in the parathyroid disease group the therapeutic strategy (medical therapy vs surgery) was changed in 18/48 patients (37.5%, P<0.01 by chi2 test of Pearson). In agreement with some previous published experiences, the combined single-day scintigraphic/USG protocol systematically adopted in a large series of consecutive patients with thyroid and parathyroid diseases, enrolled in a limited period of time, proved to significantly increase the global diagnostic accuracy and to change the therapeutic strategy in more than two third of patients with a thyroid disease and in more than one third of patients with a parathyroid disease.

Long-Term Improvement of Neurological Signs and Metabolic Dysfunction in a Mouse Model of Krabbe's Disease after Global Gene Therapy.

PubMed

Marshall, Michael S; Issa, Yazan; Jakubauskas, Benas; Stoskute, Monika; Elackattu, Vince; Marshall, Jeffrey N; Bogue, Wil; Nguyen, Duc; Hauck, Zane; Rue, Emily; Karumuthil-Melethil, Subha; Zaric, Violeta; Bosland, Maarten; van Breemen, Richard B; Givogri, Maria I; Gray, Steven J; Crocker, Stephen J; Bongarzone, Ernesto R

2018-03-07

We report a global adeno-associated virus (AAV)9-based gene therapy protocol to deliver therapeutic galactosylceramidase (GALC), a lysosomal enzyme that is deficient in Krabbe's disease. When globally administered via intrathecal, intracranial, and intravenous injections to newborn mice affected with GALC deficiency (twitcher mice), this approach largely surpassed prior published benchmarks of survival and metabolic correction, showing long-term protection of demyelination, neuroinflammation, and motor function. Bone marrow transplantation, performed in this protocol without immunosuppressive preconditioning, added minimal benefits to the AAV9 gene therapy. Contrasting with other proposed pre-clinical therapies, these results demonstrate that achieving nearly complete correction of GALC's metabolic deficiencies across the entire nervous system via gene therapy can have a significant improvement to behavioral deficits, pathophysiological changes, and survival. These results are an important consideration for determining the safest and most effective manner for adapting gene therapy to treat this leukodystrophy in the clinic. Copyright © 2018 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.

Probiotic Therapy in Preventing Gastrointestinal Complications in Patients Undergoing Chemotherapy and Pelvic Radiation Therapy

ClinicalTrials.gov

2016-07-01

Cognitive/Functional Effects; Constipation, Impaction, and Bowel Obstruction; Diarrhea; Fatigue; Gastrointestinal Complications; Psychosocial Effects of Cancer and Its Treatment; Unspecified Adult Solid Tumor, Protocol Specific

Involved-Node Proton Therapy in Combined Modality Therapy for Hodgkin Lymphoma: Results of a Phase 2 Study

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

Hoppe, Bradford S., E-mail: bhoppe@floridaproton.org; Flampouri, Stella; Zaiden, Robert

2014-08-01

Purpose: This study describes the early clinical outcomes of a prospective phase 2 study of consolidative involved-node proton therapy (INPT) as a component of combined-mode therapy in patients with stages I to III Hodgkin lymphoma (HL) with mediastinal involvement. Methods and Materials: Between September 2009 and June 2013, 15 patients with newly diagnosed HL received INPT after completing chemotherapy in an institutional review board-approved protocol comparing the dosimetric impact of PT with those of three-dimensional conformal radiation therapy (3DCRT) and intensity modulated RT. Based on {sup 18}F-Fluorodeoxyglucose positron emission tomography/computed tomography ({sup 18}F-FDG PET/CT) response, 5 children received 15 to 25.5more » cobalt Gy equivalent (CGE) of INPT after receiving 4 cycles of Adriamycin, Bleomycin, Vincristine, Etoposide, Prednisone, Cyclophosphamide or Vincristine, adriamycin, methotrexate, Prednisone chemotherapy, and 10 adults received 30.6 to 39.6 CGE of INPT after 3 to 6 cycles of Adriamycin, Bleomycine, Vinblastine, Dacarbazine. Patients were routinely evaluated for toxicity during and after treatment, using Common Terminology Criteria for Adverse Events, version 3.0, and for relapse by physical examination and routine imaging. Relapse-free survival (RFS) and event-free survival (EFS) rates were calculated using the Kaplan-Meier method from the time of diagnosis. Results: The median follow-up was 37 months (range, 26-55). Two events occurred during follow-up: 1 relapse (inside and outside the targeted field) and 1 transformation into a primary mediastinal large B cell lymphoma. The 3-year RFS rate was 93%, and the 3-year EFS rate was 87%. No acute or late grade 3 nonhematologic toxicities were observed. Conclusions: Although decades of follow-up will be needed to realize the likely benefit of PT in reducing the risk of radiation-induced late effects, PT following chemotherapy in patients with HL is well-tolerated, and disease outcomes were similar to those of conventional photon therapy.« less

Effectiveness of topical silicone gel and pressure garment therapy for burn scar prevention and management in children: study protocol for a randomised controlled trial.

PubMed

Wiseman, Jodie; Simons, Megan; Kimble, Roy; Ware, Robert; McPhail, Steven; Tyack, Zephanie

2017-02-16

Abnormal scar development following burn injury can cause substantial physical and psychological distress to children and their families. Common burn scar prevention and management techniques include silicone therapy, pressure garment therapy, or a combination of both. Currently, no definitive, high-quality evidence is available for the effectiveness of topical silicone gel or pressure garment therapy for the prevention and management of burn scars in the paediatric population. Thus, this study aims to determine the effectiveness of these treatments in children. A randomised controlled trial will be conducted at a large tertiary metropolitan children's hospital in Australia. Participants will be randomised to one of three groups: Strataderm® topical silicone gel only, pressure garment therapy only, or combined Strataderm® topical silicone gel and pressure garment therapy. Participants will include 135 children (45 per group) up to 16 years of age who are referred for scar management for a new burn. Children up to 18 years of age will also be recruited following surgery for burn scar reconstruction. Primary outcomes are scar itch intensity and scar thickness. Secondary outcomes include scar characteristics (e.g. colour, pigmentation, pliability, pain), the patient's, caregiver's and therapist's overall opinion of the scar, health service costs, adherence, health-related quality of life, treatment satisfaction and adverse effects. Measures will be completed on up to two sites per person at baseline and 1 week post scar management commencement, 3 months and 6 months post burn, or post burn scar reconstruction. Data will be analysed using descriptive statistics and univariate and multivariate regression analyses. Results of this study will determine the effectiveness of three noninvasive scar interventions in children at risk of, and with, scarring post burn or post reconstruction. Australian New Zealand Clinical Trials Registry, ACTRN12616001100482 . Registered on 5 August 2016.

Nonpainful wide-area compression inhibits experimental pain.

PubMed

Honigman, Liat; Bar-Bachar, Ofrit; Yarnitsky, David; Sprecher, Elliot; Granovsky, Yelena

2016-09-01

Compression therapy, a well-recognized treatment for lymphoedema and venous disorders, pressurizes limbs and generates massive non-noxious afferent sensory barrages. The aim of this study was to study whether such afferent activity has an analgesic effect when applied on the lower limbs, hypothesizing that larger compression areas will induce stronger analgesic effects, and whether this effect correlates with conditioned pain modulation (CPM). Thirty young healthy subjects received painful heat and pressure stimuli (47°C for 30 seconds, forearm; 300 kPa for 15 seconds, wrist) before and during 3 compression protocols of either SMALL (up to ankles), MEDIUM (up to knees), or LARGE (up to hips) compression areas. Conditioned pain modulation (heat pain conditioned by noxious cold water) was tested before and after each compression protocol. The LARGE protocol induced more analgesia for heat than the SMALL protocol (P < 0.001). The analgesic effect interacted with gender (P = 0.015). The LARGE protocol was more efficient for females, whereas the MEDIUM protocol was more efficient for males. Pressure pain was reduced by all protocols (P < 0.001) with no differences between protocols and no gender effect. Conditioned pain modulation was more efficient than the compression-induced analgesia. For the LARGE protocol, precompression CPM efficiency positively correlated with compression-induced analgesia. Large body area compression exerts an area-dependent analgesic effect on experimental pain stimuli. The observed correlation with pain inhibition in response to robust non-noxious sensory stimulation may suggest that compression therapy shares similar mechanisms with inhibitory pain modulation assessed through CPM.

Is reducing variability of blood glucose the real but hidden target of intensive insulin therapy?

PubMed

Egi, Moritoki; Bellomo, Rinaldo; Reade, Michael C

2009-01-01

Since the first report that intensive insulin therapy reduced mortality in selected surgical critically ill patients, lowering of blood glucose levels has been recommended as a means of improving patient outcomes. In this initial Leuven trial, blood glucose control by protocol using insulin was applied to 98.7% of patients in the intensive group but to only 39.2% (P < 0.0001) of patients in the control group. If appropriately applied, such protocols should decrease both the mean blood glucose concentration and its variability (variation of blood glucose concentration). Thus, it is logically possible that the benefit of intensive insulin therapy in the first Leuven trial was due to a decrease in mean glucose levels, a decrease in their variability, or both. Several recent studies have confirmed significant associations between variability of blood glucose levels and patient outcomes. Decreasing the variability of blood glucose levels might be an important dimension of glucose management, a possible mechanism by which an intensive insulin protocol exerts its putative beneficial effects, and an important goal of glucose management in the intensive care unit. Clinicians need to be aware of this controversy when considering the application of intensive insulin therapy and interpreting future trials.

Clinical trials for treating recurrent head and neck cancer with boron neutron capture therapy using the Tsing-Hua Open Pool Reactor.

PubMed

Wang, Ling-Wei; Liu, Yen-Wan Hsueh; Chou, Fong-In; Jiang, Shiang-Huei

2018-06-19

Head and neck (HN) cancer is an endemic disease in Taiwan, China. Locally recurrent HN cancer after full-dose irradiation poses a therapeutic challenge, and boron neutron capture therapy (BNCT) may be a solution that could provide durable local control with tolerable toxicity. The Tsing-Hua Open Pool Reactor (THOR) at National Tsing-Hua University in Hsin-Chu, provides a high-quality epithermal neutron source for basic and clinical BNCT research. Our first clinical trial, entitled "A phase I/II trial of boron neutron capture therapy for recurrent head and neck cancer at THOR", was carried out between 2010 and 2013. A total of 17 patients with 23 recurrent HN tumors who had received high-dose photon irradiation were enrolled in the study. The fructose complex of L-boronophenylalanine was used as a boron carrier, and a two-fraction BNCT treatment regimen at 28-day intervals was used for each patient. Toxicity was acceptable, and although the response rate was high (12/17), re-recurrence within or near the radiation site was common. To obtain better local control, another clinical trial entitled "A phase I/II trial of boron neutron capture therapy combined with image-guided intensity-modulated radiotherapy (IG-IMRT) for locally recurrent HN cancer" was initiated in 2014. The first administration of BNCT was performed according to our previous protocol, and IG-IMRT was initiated 28 days after BNCT. As of May 2017, seven patients have been treated with this combination. The treatment-related toxicity was similar to that previously observed with two BNCT applications. Three patients had a complete response, but locoregional recurrence was the major cause of failure despite initially good responses. Future clinical trials combining BNCT with other local or systemic treatments will be carried out for recurrent HN cancer patients at THOR.

Penta-therapy for severe acute hyperlipidemic pancreatitis: A retrospective chart review over a 10-year period.

PubMed

Lu, Jian; Xie, Yun; Du, Jiang; Kang, Mei; Jin, Wei; Li, Yan; Xie, Hui; Cheng, Ruijie; Tian, Rui; Wang, Ruilan

2018-02-03

The purpose of our study is to evaluate the efficacy of penta-therapy for HL-SAP in a retrospective study. Retrospective study between January 2007 and December 2016 in a hospital intensive care unit. HL-SAP patients were assigned to conventional treatment alone (the control group) or conventional treatment with the experimental protocol (the penta-therapy group) consists of blood purification, antihyperlipidemic agents, low-molecular weight heparin, insulin, covering the whole abdomen with Pixiao (a traditional Chinese medicine). Serum triglyceride, serum calcium, APACHE II score, SOFA score, Ranson score, and other serum biomarkers were evaluated. The hospital length of stay, local complications, systematic complications, rate of recurrence, overall mortality, and operation rate were considered clinical outcomes. 63 HL-SAP patients received conventional treatment alone (the control group) and 25 patients underwent penta- therapy combined with conventional treatment (the penta-therapy group). Serum amylase, serum triglyceride, white blood cell count, C-reactive protein, and blood sugar were significantly reduced, while serum calcium was significantly increased with penta-therapy. The changes in serum amylase, serum calcium were significantly different between the penta-therapy and control group on 7th day after the initiation of treatment. The reduction in serum triglyceride in the penta-therapy group on the second day and 7th day were greater than the control group. Patients in the penta-therapy group had a significantly shorter length of hospital stay. This study suggests that the addition of penta-therapy to conventional treatment for HL-SAP may be superior to conventional treatment alone for improvement of serum biomarkers and clinical outcomes. Copyright © 2018. Published by Elsevier Inc.

Comparison of Brunnstrom movement therapy and Motor Relearning Program in rehabilitation of post-stroke hemiparetic hand: a randomized trial.

PubMed

Pandian, Shanta; Arya, Kamal Narayan; Davidson, E W Rajkumar

2012-07-01

Motor recovery of the hand usually plateaus in chronic stroke patients. Various conventional and contemporary approaches have been used to rehabilitate the hand post-stroke. However, the evidence for their effectiveness is still limited. To compare the hand therapy protocols based on Brunnstrom approach and motor relearning program in rehabilitation of the hand of chronic stroke patients. Randomized trial. Outpatients attending the occupational therapy department of a rehabilitation institute. 30 post-stroke subjects (35.06 ± 14.52 months) were randomly assigned into two equal groups (Group A and Group B), Outcome Measures: Brunnstrom recovery stages of hand (BRS-H), Fugl-Meyer assessment: wrist and hand (FMA-WH). Group A received Brunnstrom hand manipulation (BHM). BHM is the hand treatment protocol of the Brunnstrom movement therapy, which uses synergies and reflexes to develop voluntary motor control. Group B received the Motor Relearning Program (MRP) based hand protocol. MRP is the practice of specific motor skills, which results in the ability to perform a task. Active practice of context-specific motor task such as reaching and grasping helps regain the lost motor functions. Both the therapy protocols were effective in rehabilitation of the hand (BRS-H; p = 0.003 to 0.004, FMA-WH; p < 0.001). However, the results were statistically significant in favor of group A undergoing BHM for FMA-WH (p < 0.004) and FMA item VIII (hand motor recovery) (p < 0.033). BHM was found to be more effective than MRP in rehabilitation of the hand in chronic post-stroke patients. Copyright © 2011 Elsevier Ltd. All rights reserved.

Rectal Toxicity After Proton Therapy For Prostate Cancer: An Analysis of Outcomes of Prospective Studies Conducted at the University of Florida Proton Therapy Institute

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

Colaco, Rovel J.; Hoppe, Bradford S.; Flampouri, Stella

2015-01-01

Purpose: Study goals were to characterize gastrointestinal effects of proton therapy (PT) in a large cohort of patients treated for prostate cancer, identify factors associated with rectal bleeding (RB), and compare RB between patients receiving investigational protocols versus those in outcome-tracking protocols. Methods and Materials: A total of 1285 consecutive patients were treated with PT between August 2006 and May 2010. Potential pre-existing clinical and treatment-related risk factors for rectal toxicity were recorded. Common Terminology Criteria for Adverse Events version 3.0 was used to score toxicity. Results: Transient RB was the predominant grade 2 or higher (GR2+) toxicity after PT,more » accounting for 95% of gastrointestinal events. GR1 RB occurred in 217 patients (16.9%), GR2 RB in 187 patients (14.5%), and GR3 in 11 (0.9%) patients. There were no GR4 or GR5 events. Univariate analyses showed correlations between GR2+ RB and anticoagulation therapy (P=.008) and rectal and rectal wall dose-volume histogram (DVH) parameters (P<.001). On multivariate analysis, anticoagulation therapy (P=.0034), relative volume of rectum receiving 75 Gy (V75; P=.0102), and relative rectal wall V75 (P=.0017) were significant predictors for G2+ RB. Patients treated with investigational protocols had toxicity rates similar to those receiving outcome-tracking protocols. Conclusions: PT was associated with a low rate of GR2+ gastrointestinal toxicity, predominantly transient RB, which was highly correlated with anticoagulation and rectal DVH parameters. Techniques that limit rectal exposure should be used when possible.« less

Evolutionary cognitive therapy versus standard cognitive therapy for depression: a protocol for a blinded, randomized, superiority clinical trial.

PubMed

Giosan, Cezar; Cobeanu, Oana; Mogoase, Cristina; Muresan, Vlad; Malta, Loretta S; Wyka, Katarzyna; Szentagotai, Aurora

2014-03-19

Depression is estimated to become the leading cause of disease burden globally by 2030. Despite existing efficacious treatments (both medical and psychotherapeutic), a large proportion of patients do not respond to therapy. Recent insights from evolutionary psychology suggest that, in addition to targeting the proximal causes of depression (for example, targeting dysfunctional beliefs by cognitive behavioral therapy), the distal or evolutionary causes (for example, inclusive fitness) should also be addressed. A randomized superiority trial is conducted to develop and test an evolutionary-driven cognitive therapy protocol for depression, and to compare its efficacy against standard cognitive therapy for depression. Romanian-speaking adults (18 years or older) with elevated Beck Depression Inventory (BDI) scores (>13), current diagnosis of major depressive disorder or major depressive episode (MDD or MDE), and MDD with comorbid dysthymia, as evaluated by the Structured Clinical Interview for DSM-IV (SCID), are included in the study. Participants are randomized to one of two conditions: 1) evolutionary-driven cognitive therapy (ED-CT) or 2) cognitive therapy (CT). Both groups undergo 12 psychotherapy sessions, and data are collected at baseline, mid-treatment, post-treatment, and the 3-month follow-up. Primary outcomes are depressive symptomatology and a categorical diagnosis of depression post-treatment. This randomized trial compares the newly proposed ED-CT with a classic CT protocol for depression. To our knowledge, this is the first attempt to integrate insights from evolutionary theories of depression into the treatment of this condition in a controlled manner. This study can thus add substantially to the body of knowledge on validated treatments for depression. Current Controlled Trials ISRCTN64664414The trial was registered in June 2013. The first participant was enrolled on October 3, 2012.

[Clinical Evaluation of Diagnostic and Treatment Protocol of Idiopathic Retroperitoneal Fibrosis Incorporating Consideration of Possible IgG4-Related Disease].

PubMed

Iyoki, Takaya; Maehana, Takeshi; Tanaka, Toshiaki; Yamamoto, Motohisa; Takahashi, Hiroki; Masumori, Naoya

2017-11-01

About half of idiopathic retroperitoneal fibrosis might be classified as a IgG4-related disease, a newly characterized disease that is especially known to be sensitive to steroid therapy. We developed a new protocol for diagnosis and treatment of retroperitoneal fibrosis, which included aggressive diagnosis of IgG4- related disease. We retrospectively reviewed 22 cases with idiopathic retroperitoneal fibrosis that were diagnosed and treated according to our protocol. Of them, 10 patients (45.5%) had no evidence of IgG4- related disease (non-IgG4RD group), whereas 12 patients (54.5%) were diagnosed with IgG4-related disease (IgG4RD group). All patients received steroid therapy, and 13 patients (59.1%) underwent ureteral stenting or received prednisolone (PNS). There was no severe adverse event and planned steroid therapy was completed in all patients. In principle, maintenance steroid therapy was continued after induction therapy in the IgG4RD group, whereas steroid therapy was discontinued in the non-IgG4RD group. Regression of retroperitoneal plaque was achieved in all 22 patients. Four (57.1%) out of 7 patients and 3 (50.0%) out of 6 patients achieved freedom from ureteral stent or PNS in the non-IgG4RD group and IgG4RD group, respectively. All 3 patients with PNS became catheter-free after treatment, whereas only 4 (40.0%) of the 10 patients withureteral stent could become stent-free. Steroid therapy could be discontinued in 7 patients (70.0%) in the non-IgG4RD group. The results of this study suggest that similar efficacy of steroid therapy can be expected in the non-IgG4RD group and IgG4RD group.

Optimizing Immunosuppressive Regimens Among Living-Donor Renal Transplant Recipients.

PubMed

Bakr, Mohamed Adel; Nagib, Ayman Maher; Gheith, Osama Ashry; Hamdy, Ahmed Farouk; Refaie, Ayman Fathi; Donia, Ahmed Farouk; Neamatalla, Ahmed Hassan; Eldahshan, Khaled Farouk; Denewar, Ahmed Abdelfattah; Abbas, Mohamed Hamed; Mostafa, Amany Ismail; Ghoneim, Mohamed Ahmed

2017-02-01

We review different immunosuppressant protocols used for living-donor kidney transplant recipients at our center. Many prospective randomized studies from our center have been reported between March 1976 and 2016, with more than 2700 renal transplant procedures conducted. The first study was a prospective randomized trial of azathioprine versus cyclosporine. The second study compared triple therapy (prednisolone + azathioprine + cyclosporine) versus conventional therapy (prednisolone + azathioprine). The third study was a cost-saving study, in which 100 patients received ketoconazole along with the triple regimen. Another trial demonstrated the advantages of a microemulsion form of cyclosporine. A subsequent trial compared calcineurin inhibitor minimization versus avoidance protocols. Rescue therapies were carried out to intensify immunosuppressive regimens after repeated rejection. In addition, steroid-free regimens were evaluated during both short- and long-term treatment. A recent trial reported a step-forward avoidance protocol with a calcineurin inhibitor and a steroid-free regimen, whereas another current study is the TRANSFORM one. The rationale behind antibody therapy was tho roughly evaluated among living-donor renal trans plant recipients with different agents, including basiliximab, daclizumab, antithymocyte globulin, and alemtuzumab. Earlier studies have demonstrated the efficacy of conventional regimens without induction therapy, especially in longer follow-up. The standard triple therapy has emerged with intensified immunosuppressive and lowered dose of each drug, especially cyclosporine. In minimization studies, no significant differences were encountered regarding patient and graft survival, even in the long-term. Steroid avoidance was safe and effective. Calcineurin inhibitors and steroid-free regimens have shown comparable patient and graft survival. Induction therapy has lowered the incidence and severity of acute rejection. A better 5-year graft survival and less posttransplant complications have been achieved with steroid avoidance after induction with basiliximab. Induction therapy did not affect graft and patient survival rates despite lowered incidence and severity of acute rejections.

Alternative therapies for metastatic breast cancer: multimodal approach targeting tumor cell heterogeneity.

PubMed

Sambi, Manpreet; Haq, Sabah; Samuel, Vanessa; Qorri, Bessi; Haxho, Fiona; Hill, Kelli; Harless, William; Szewczuk, Myron R

2017-01-01

One of the primary challenges in developing effective therapies for malignant tumors is the specific targeting of a heterogeneous cancer cell population within the tumor. The cancerous tumor is made up of a variety of distinct cells with specialized receptors and proteins that could potentially be viable targets for drugs. In addition, the diverse signals from the local microenvironment may also contribute to the induction of tumor growth and metastasis. Collectively, these factors must be strategically studied and targeted in order to develop an effective treatment protocol. Targeted multimodal approaches need to be strategically studied in order to develop a treatment protocol that is successful in controlling tumor growth and preventing metastatic burden. Breast cancer, in particular, presents a unique problem because of the variety of subtypes of cancer that can arise and the multiple drug targets that could be exploited. For example, the tumor stage and subtypes often dictate the appropriate treatment regimen. Alternate multimodal therapies should consider the importance of time-dependent drug administration, as well as targeting the local and systemic tumor environment. Many reviews and papers have briefly touched on the clinical implications of this cellular heterogeneity; however, there has been very little discussion on the development of study models that reflect this diversity and on multimodal therapies that could target these subpopulations. Here, we summarize the current understanding of the origins of intratumoral heterogeneity in breast cancer subtypes, and its implications for tumor progression, metastatic potential, and treatment regimens. We also discuss the advantages and disadvantages of utilizing specific breast cancer models for research, including in vitro monolayer systems and three-dimensional mammospheres, as well as in vivo murine models that may have the capacity to encompass this heterogeneity. Lastly, we summarize some of the current advancements in the development of multitarget therapeutics that have shown promising results in clinical and preclinical studies when used alone or in combination with traditional regimens of surgery, chemotherapy, and/or radiation.

It is not only the empty vials that go into the garbage can during chemotherapy drugs preparation: a cost analysis of unused chemotherapy drugs in cancer treatment.

PubMed

Ata, A; Abali, H; Yengel, E; Arican, A

2012-01-01

Cancer therapy is a costly treatment. Costs of drugs used in cancer therapy are gradually increasing with the addition of new and expensive drugs. This fact imposes obligation on reasonable drug usage. Occasionally, all of the prescribed drugs are not used for various reasons, and a number of drugs can be left over. In this study, we aimed to calculate the costs of unused chemotherapeutic drugs in our oncology clinics. A total of 117 patients with 17 different types of cancer were administered 32 cancer therapy protocols during 2 months. After administration of ideal doses of the prescribed drugs calculated on an individual basis, the number of unused drug doses in the packages was recorded and the costs of the unused drugs were calculated based on current prices of the drugs. The cumulative cost of the unused drugs calculated for all patients was US dollars (USD) 6406.93, and average cost of the drug per capita was USD 54.76. Minimal and maximal unused drug costs per drug were USD 0.29 for 5-fluorouracil, and USD 247.12 for bevacizumab, respectively. Minimal increase in drug costs per recipe was USD 0.50 for a prescription containing cyclophosphamide and 5-fluorouracil, while the total cost of bevacizumab plus irinotecan combination increased tremendously to USD 309.12. Among chemotherapeutic protocols the cheapest one was AC (adriamycin, cyclophosphamide) with USD 4.77, while the most expensive one (USD 116.02) was FOLFIRI-B (5-fluorouracil, calcium folinate, irinotecan, and bevacizumab). The important financial burden of unused drugs goes unrecognized among routine chemotherapeutic applications. In order to be able to avoid this extravagance, drug industry, prescribing physicians, and practice nurses must assume important roles.

DNA Methylation Adds Prognostic Value to Minimal Residual Disease Status in Pediatric T-Cell Acute Lymphoblastic Leukemia.

PubMed

Borssén, Magnus; Haider, Zahra; Landfors, Mattias; Norén-Nyström, Ulrika; Schmiegelow, Kjeld; Åsberg, Ann E; Kanerva, Jukka; Madsen, Hans O; Marquart, Hanne; Heyman, Mats; Hultdin, Magnus; Roos, Göran; Forestier, Erik; Degerman, Sofie

2016-07-01

Despite increased knowledge about genetic aberrations in pediatric T-cell acute lymphoblastic leukemia (T-ALL), no clinically feasible treatment-stratifying marker exists at diagnosis. Instead patients are enrolled in intensive induction therapies with substantial side effects. In modern protocols, therapy response is monitored by minimal residual disease (MRD) analysis and used for postinduction risk group stratification. DNA methylation profiling is a candidate for subtype discrimination at diagnosis and we investigated its role as a prognostic marker in pediatric T-ALL. Sixty-five diagnostic T-ALL samples from Nordic pediatric patients treated according to the Nordic Society of Pediatric Hematology and Oncology ALL 2008 (NOPHO ALL 2008) protocol were analyzed by HumMeth450K genome wide DNA methylation arrays. Methylation status was analyzed in relation to clinical data and early T-cell precursor (ETP) phenotype. Two distinct CpG island methylator phenotype (CIMP) groups were identified. Patients with a CIMP-negative profile had an inferior response to treatment compared to CIMP-positive patients (3-year cumulative incidence of relapse (CIR3y ) rate: 29% vs. 6%, P = 0.01). Most importantly, CIMP classification at diagnosis allowed subgrouping of high-risk T-ALL patients (MRD ≥0.1% at day 29) into two groups with significant differences in outcome (CIR3y rates: CIMP negative 50% vs. CIMP positive 12%; P = 0.02). These groups did not differ regarding ETP phenotype, but the CIMP-negative group was younger (P = 0.02) and had higher white blood cell count at diagnosis (P = 0.004) compared with the CIMP-positive group. CIMP classification at diagnosis in combination with MRD during induction therapy is a strong candidate for further risk classification and could confer important information in treatment decision making. © 2016 Wiley Periodicals, Inc.

The Rate and Shape of Change in Binge Eating Episodes and Weight: An Effectiveness Trial of Emotionally Focused Group Therapy for Binge-Eating Disorder.

PubMed

Compare, Angelo; Tasca, Giorgio A

2016-01-01

This study investigated the phases of change and the relationship between binge eating (BE) episodes and weight across 20 weeks of emotionally focused group therapy (EFGT) and combined therapy (CT) of EFGT plus dietary counselling for BE disorder. We used a non-randomized observational study design that included 118 obese adult patients with BE disorder who were treated by manualized therapy protocols. Participants were assigned to treatment condition (EFGT or CT) based on consensus among clinicians. Participants were assessed weekly during the 20 weeks of therapy for weight and BE episodes and at pre-treatment and 6 months post-treatment. Binge eating episodes and weight significantly declined during EFGT and CT. Compared with EFGT, CT resulted in more rapid weight loss across weeks of therapy. BE episodes and weight significantly covaried, and their positive association increased as sessions progressed. Change in BE episodes and weight during treatment was best modelled by a cubic growth curve showing a slow rate of change in early sessions, a faster rate of change in middle sessions and a slower rate of change in late sessions. This cubic modelling of change was associated with better outcomes 6 months post-treatment. Cubic modelling of change supported a three-stage model of EFGT and CT, and the cubic trajectory was associated with better outcomes at follow-up. The addition of dietary counselling to EFGT resulted in earlier response to treatment in terms of BE episodes and weight among those in the CT condition. Decline in binge eating (BE) episodes is related to decline in weight, and this relationship was greater towards the end of treatment. Emotionally focused group therapy plus dietary counselling that targets both affect regulation and nutritional problems resulted in faster rate of response early in treatment both in terms of BE episodes and weight. Combined emotionally focused group therapy and dietary counselling may provide clinicians with an additional approach to treating BE disorder. Copyright © 2014 John Wiley & Sons, Ltd.

Implementation of an Intensive Care Unit-Specific Alcohol Withdrawal Syndrome Management Protocol Reduces the Need for Mechanical Ventilation.

PubMed

Heavner, Jason J; Akgün, Kathleen M; Heavner, Mojdeh S; Eng, Claire C; Drew, Matthew; Jackson, Peter; Pritchard, David; Honiden, Shyoko

2018-05-25

Alcohol use disorders are prevalent and put patients at risk for developing alcohol withdrawal syndrome (AWS). Treatment of AWS with a symptom-triggered protocol standardizes management and may avoid AWS-related complications. The objective of this study was to evaluate whether implementation of an intensive care unit (ICU)-specific, symptom-triggered protocol for management of AWS was associated with improved clinical outcomes and, in particular, would reduce the risk of patients with AWS requiring mechanical ventilation. Retrospective pre-post-protocol implementation study. Thirty-six-bed, closed medical ICU (MICU) at a large, tertiary care, teaching hospital in an urban setting. A total of 233 adults admitted to the MICU with any diagnosis of alcohol use disorders based on International Classification of Diseases, Ninth Revision codes and who received at least one dose of any benzodiazepine; of these patients, 139 were in the pre-protocol era (August 2009-January 2010 and August 2010-January 2011), and 94 were in the post-protocol era (August 2012-January 2013), after implementation of the Yale Alcohol Withdrawal Protocol (YAWP) in April 2012. The YAWP pairs a modified Minnesota Detoxification Scale with an order set that includes benzodiazepine dosing regimens and suggests adjuvant therapies. AWS was the primary reason for ICU admission (107/233 patients [45.9%]) and did not significantly vary between eras (P=0.2). Of the 233 patients included, 81.1% were male and 67.0% were white, which did not significantly differ by study era. Severity of illness at MICU admission did not significantly differ between patients in the pre-protocol and post-protocol eras (median [interquartile range] Acute Physiology and Chronic Health Evaluation [APACHE] II scores of 12 [9-17] and 12.5 [7-16], respectively, p=0.4). Median lorazepam-equivalent dose per MICU day, duration of benzodiazepine infusion, and use of adjuvant therapy were not significantly different between eras. MICU intubation was less common in the post-protocol era (36/139 patients [25.9%] pre-protocol vs 8/94 patients [8.5%] post-protocol, p=0.0009). ICU-related pneumonia was also decreased in the post-protocol era (30/139 patients [21.6%] pre-protocol vs 10/94 patients [10.6%] post-protocol, p=0.03). After adjusting for demographics, adjuvant therapies, and Acute Physiology and Chronic Health Evaluation II scores, protocol implementation was associated with a decreased odds of MICU intubation (odds ratio 0.13; 95% confidence interval 0.04-0.39). Implementation of YAWP was associated with a decreased risk of MICU intubation in patients at risk for AWS. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Delivery of the Wilbarger Protocol: A Survey of Pediatric Occupational Therapy Practitioners

ERIC Educational Resources Information Center

Lancaster, Stephanie; Zachry, Anne; Duck, Ashleigh; Harris, Alexandria; Page, Ellen; Sanders, Jordan

2016-01-01

The Wilbarger Therapressure Program is a commonly used treatment approach utilized by occupational therapy professionals for the treatment of sensory defensiveness. The purpose of the current study was to investigate occupational therapy practitioners' sources of training in the administration of Wilbarger Therapressure Program, the uniformity of…

Endogenous Heat-Shock Protein Induction with or Without Radiofrequency Ablation or Cryoablation in Patients with Stage IV Melanoma.

PubMed

Domingo-Musibay, Evidio; Heun, James M; Nevala, Wendy K; Callstrom, Matthew; Atwell, Thomas; Galanis, Evanthia; Erickson, Lori A; Markovic, Svetomir N

2017-09-01

Percutaneous thermal ablation combined with in situ granulocyte-macrophage colony-stimulating factor cytokine therapy was technically feasible and well tolerated.No significant clinical or immunologic responses were seen. Melanoma tumor-derived heat-shock proteins (HSPs) and HSP-peptide complexes can elicit protective antitumor responses. The granulocyte-macrophage colony-stimulating factor (GM-CSF) chemokine can also promote uptake and processing by professional antigen presenting cells (APCs). On this basis, we designed a pilot study of percutaneous thermal ablation as a means to induce heat-shock protein vaccination plus GM-CSF to determine safety and preliminary antitumor activity of this combination. This study was designed to assess overall safety of percutaneous ablation combined with GM-CSF for unresectable, metastatic melanoma including uveal and mucosal types. All patients received heat-shock therapy (42°C for 30 minutes), then received one of three treatments: (a) intralesional GM-CSF (500 mcg standard dose); (b) radiofrequency ablation (RFA) + GM-CSF; or (c) cryoablation plus GM-CSF. The primary endpoint of the study was the induction of endogenous HSP70 and melanoma-specific cytotoxic T lymphocytes (CTL). Nine patients (three per study arm) were enrolled. No dose-limiting toxicity was observed as specified per protocol. All patients developed progressive disease and went on to receive alternative therapy. Median overall survival (OS) was 8.2 months (95% confidence interval [CI] 2-17.2). The study was not powered to detect a difference in clinical outcome among treatment groups. Percutaneous thermal ablation plus GM-CSF was well tolerated, technically feasible, and demonstrated an acceptable adverse event profile comparable to conventional RFA and cryoablation. While HSP70 was induced following therapy, the degree of HSP70 elevation was not associated with clinical outcome or induced CTL responses. While percutaneous thermal ablation plus GM-CSF combinations including checkpoint inhibitors could be considered in future studies, the use of GM-CSF remains experimental and for use in the context of clinical trials. © AlphaMedPress; the data published online to support this summary is the property of the authors.

Advantages and pitfalls of combining intravenous antithrombin with nebulized heparin and tissue plasminogen activator in acute respiratory distress syndrome.

PubMed

Rehberg, Sebastian; Yamamoto, Yusuke; Sousse, Linda E; Jonkam, Collette; Cox, Robert A; Prough, Donald S; Enkhbaatar, Perenlei

2014-01-01

Pulmonary coagulopathy has become an important therapeutic target in adult respiratory distress syndrome (ARDS). We hypothesized that combining intravenous recombinant human antithrombin (rhAT), nebulized heparin, and nebulized tissue plasminogen activator (TPA) more effectively improves pulmonary gas exchange compared with a single rhAT infusion, while maintaining the anti-inflammatory properties of rhAT in ARDS. Therefore, the present prospective, randomized experiment was conducted using an established ovine model. Following burn and smoke inhalation injury (40% of total body surface area, third-degree flame burn, and 4 × 12 breaths of cold cotton smoke), 18 chronically instrumented sheep were randomly assigned to receive intravenous saline plus saline nebulization (control), intravenous rhAT (6 IU/kg/h) started 1 hour after injury plus saline nebulization (AT i.v.) or intravenous rhAT combined with nebulized heparin (10,000 IU every 4 hours, started 2 hours after injury), and nebulized TPA (2 mg every 4 hours, started 4 hours after injury) (triple therapy, n = 6 each). All animals were mechanically ventilated and fluid resuscitated according to standard protocols during the 48-hour study period. Both treatment approaches attenuated ARDS compared with control animals. Notably, triple therapy was associated with an improved PaO2/FiO2 ratio (p = 0.007), attenuated pulmonary obstruction (p = 0.02) and shunting (p = 0.025), as well as reduced ventilatory pressures (p < 0.05 each) versus AT i.v. at 48 hours. However, the anti-inflammatory effects of sole AT i.v., namely, the inhibition of neutrophil activation (neutrophil count in the lymph and pulmonary polymorphonuclear cells, p < 0.05 vs. control each), pulmonary transvascular fluid flux (lymph flow, p = 0.004 vs. control), and systemic vascular leakage (cumulative net fluid balance, p < 0.001 vs. control), were abolished in the triple therapy group. Combining intravenous rhAT with nebulized heparin and nebulized TPA more effectively restores pulmonary gas exchange, but the anti-inflammatory effects of sole rhAT are abolished with the triple therapy. Interferences between the different anticoagulants may represent a potential explanation for these findings.

Combining visual rehabilitative training and noninvasive brain stimulation to enhance visual function in patients with hemianopia: a comparative case study.

PubMed

Plow, Ela B; Obretenova, Souzana N; Halko, Mark A; Kenkel, Sigrid; Jackson, Mary Lou; Pascual-Leone, Alvaro; Merabet, Lotfi B

2011-09-01

To standardize a protocol for promoting visual rehabilitative outcomes in post-stroke hemianopia by combining occipital cortical transcranial direct current stimulation (tDCS) with Vision Restoration Therapy (VRT). A comparative case study assessing feasibility and safety. A controlled laboratory setting. Two patients, both with right hemianopia after occipital stroke damage. METHODS AND OUTCOME MEASUREMENTS: Both patients underwent an identical VRT protocol that lasted 3 months (30 minutes, twice a day, 3 days per week). In patient 1, anodal tDCS was delivered to the occipital cortex during VRT training, whereas in patient 2 sham tDCS with VRT was performed. The primary outcome, visual field border, was defined objectively by using high-resolution perimetry. Secondary outcomes included subjective characterization of visual deficit and functional surveys that assessed performance on activities of daily living. For patient 1, the neural correlates of visual recovery were also investigated, by using functional magnetic resonance imaging. Delivery of combined tDCS with VRT was feasible and safe. High-resolution perimetry revealed a greater shift in visual field border for patient 1 versus patient 2. Patient 1 also showed greater recovery of function in activities of daily living. Contrary to the expectation, patient 2 perceived greater subjective improvement in visual field despite objective high-resolution perimetry results that indicated otherwise. In patient 1, visual function recovery was associated with functional magnetic resonance imaging activity in surviving peri-lesional and bilateral higher-order visual areas. Results of preliminary case comparisons suggest that occipital cortical tDCS may enhance recovery of visual function associated with concurrent VRT through visual cortical reorganization. Future studies may benefit from incorporating protocol refinements such as those described here, which include global capture of function, control for potential confounds, and investigation of underlying neural substrates of recovery. Copyright © 2011 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.

Clinical outcome comparison of immediate blanket treatment versus a delayed pathogen-based treatment protocol for clinical mastitis in a New York dairy herd.

PubMed

Vasquez, A K; Nydam, D V; Capel, M B; Eicker, S; Virkler, P D

2017-04-01

The purpose was to compare immediate intramammary antimicrobial treatment of all cases of clinical mastitis with a selective treatment protocol based on 24-h culture results. The study was conducted at a 3,500-cow commercial farm in New York. Using a randomized design, mild to moderate clinical mastitis cases were assigned to either the blanket therapy or pathogen-based therapy group. Cows in the blanket therapy group received immediate on-label intramammary treatment with ceftiofur hydrochloride for 5 d. Upon receipt of 24 h culture results, cows in the pathogen-based group followed a protocol automatically assigned via Dairy Comp 305 (Valley Agricultural Software, Tulare, CA): Staphylococcus spp., Streptococcus spp., or Enterococcus spp. were administered on-label intramammary treatment with cephapirin sodium for 1 d. Others, including cows with no-growth or gram-negative results, received no treatment. A total of 725 cases of clinical mastitis were observed; 114 cows were not enrolled due to severity. An additional 122 cases did not meet inclusion criteria. Distribution of treatments for the 489 qualifying events was equal between groups (pathogen-based, n = 246; blanket, n = 243). The proportions of cases assigned to the blanket and pathogen-based groups that received intramammary therapy were 100 and 32%, respectively. No significant differences existed between blanket therapy and pathogen-based therapy in days to clinical cure; means were 4.8 and 4.5 d, respectively. The difference in post-event milk production between groups was not statistically significant (blanket therapy = 34.7 kg; pathogen-based = 35.4 kg). No differences were observed in test-day linear scores between groups; least squares means of linear scores was 4.3 for pathogen-based cows and 4.2 for blanket therapy cows. Odds of survival 30 d postenrollment was similar between groups (odds ratio of pathogen-based = 1.6; 95% confidence interval: 0.7-3.7) as was odds of survival to 60 d (odds ratio = 1.4; 95% confidence interval: 0.7-2.6). The one significant difference found for the effect of treatment was in hospital days; pathogen-based cows experienced, on average, 3 fewer days than blanket therapy cows. A majority (68.5%) of moderate and mild clinical cases would not have been treated if all cows on this trial were enrolled in a pathogen-based protocol. The use of a strategic treatment protocol based on 24-h postmastitis pathogen results has potential to efficiently reduce antimicrobial use. Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

RiMINI - the influence of rifaximin on minimal hepatic encephalopathy (MHE) and on the intestinal microbiome in patients with liver cirrhosis: study protocol for a randomized controlled trial.

PubMed

Schulz, Christian; Schütte, Kerstin; Kropf, Siegfried; Schmitt, Friedhelm C; Vasapolli, Riccardo; Kliegis, Leon M; Riegger, Antonia; Malfertheiner, Peter

2016-02-29

Hepatic encephalopathy (HE) is a clinically significant complication of liver cirrhosis impacting on the patients' quality of life. Minimal hepatic encephalopathy (MHE) is diagnosed by psychometric tests, found in up to 80 % of patients with liver cirrhosis and carries a high risk of progression to overt HE. Continuous therapy with rifaximin in combination with lactulose significantly reduces the risk of overt HE, recurrence of HE and HE-related hospitalizations in randomized, double-blind, placebo-controlled clinical trials. Rifaximin is approved for the therapy of overt HE in Germany. Treatment with lactulose has been shown to improve cognitive functions in patients with liver cirrhosis. Data from prospective clinical trials comparing the efficacy of rifaximin alone against a combination of rifaximin and lactulose in the treatment of MHE are scarce. Changes in the microbiome of the upper and lower gastrointestinal tract as a result of therapy with rifaximin have not yet been addressed in clinical studies. RiMINI is a monocentric exploratory pilot study on 60 patients with MHE as assessed by critical flicker frequency (CFF). Additionally, visual evoked potentials' (VEP) testing, electroencephalography (EEG) and psychometric testing (NCT-A) will be carried out. Patients will be randomized to treatment either with rifaximin alone (550 mg twice daily (bid) continuously for a period of 3 months) or with rifaximin (550 mg bid continuously) in combination with lactulose (30-60 ml daily) for 3 months. An esophagogastroduodenoscopy (EGD) will be performed at baseline, at the end of treatment and 6 and 12 weeks after the end of treatment to obtain gastric and duodenal biopsies and aspirates. The samples will be analyzed for their content of specific bacterial taxae by applying next generation sequencing (NGS) after rRNA isolation to identify the microbiome of the stomach and duodenum, and of the gut, in patients with liver cirrhosis and MHE before and after therapy. Differences of the effect of antibiotic therapy with rifaximin alone or in combination with lactulose on the clinical course of MHE are assessed. The trial was registered as DRKS00006359 on March 17th 2015, with the universal trial number U1111-1163-9410 and with EudraCT2013-004414-18 .

A novel somatic JAK2 kinase-domain mutation in pediatric acute lymphoblastic leukemia with rapid on-treatment development of LOH.

PubMed

Sadras, Teresa; Heatley, Susan L; Kok, Chung H; McClure, Barbara J; Yeung, David; Hughes, Timothy P; Sutton, Rosemary; Ziegler, David S; White, Deborah L

2017-10-01

We report a novel somatic mutation in the kinase domain of JAK2 (R938Q) in a high-risk pediatric case of B-cell acute lymphoblastic leukemia (ALL). The patient developed on-therapy relapse at 12 months, and interestingly, the JAK2 locus acquired loss of heterozygosity during treatment resulting in 100% mutation load. Furthermore, we show that primary ALL mononuclear cells harboring the JAK2 R938Q mutation display reduced sensitivity to the JAK1/2 ATP-competitive inhibitor ruxolitinib in vitro, compared to ALL cells that carry a more common JAK2 pseudokinase domain mutation. Our findings are in line with previous reports that demonstrate that mutations within the kinase domain of JAK2 are associated with resistance to type I JAK inhibitors. Importantly, given the recent inclusion of ruxolitinib in trial protocols for children with JAK pathway alterations, we predict that inter-patient genetic variability may result in suboptimal responses to JAK inhibitor therapy in a subset of cases. The need for alternate targeted and/or combination therapies for patients who display inherent or developed resistance to JAK inhibitor therapy will be warranted, and we propose that kinase-mutants less sensitive to type I JAK inhibitors may present a currently unexplored platform for investigation of improved therapies. Copyright © 2017. Published by Elsevier Inc.

VB-CHEP chemotherapy regimen for aggressive non-Hodgkin's lymphomas.

PubMed

Yalçin, S; Kars, A; Ozişik, Y; Tekuzman, G; Ozyilkan, O; Celik, I; Barişta, I; Güllü, I; Güler, N; Baltali, E; Firat, D

1998-10-01

Despite intensive search for the optimal combination chemotherapy for aggressive non-Hodgkin's lymphoma (NHL), the CHOP (cyclophosphamide, adriamycin, vincristine and prednisolone) regimen is still the standard therapy. We investigated the clinical efficacy of a new combination regimen consisting of vincristine, bleomycin-cyclophosphamide, adriamycin, etoposide and prednisolone (VB-CHEP) in patients with aggressive NHL. A total of 29 patients with aggressive NHL was enrolled into the protocol. Eight patients were consolidated with cisplatin and cytarabine and 5 patients received radiotherapy for bulky disease. Objective response was achieved in 82.8% of the patients. Complete remission (CR) and partial remission rates were 72.4%, and 10.3%, respectively. CR rate was significantly lower in patients with advanced stage, extranodal disease and bone marrow involvement. Median follow-up time is 34+ months; 17 patients are disease-free while 12 died and only 2 patients with CR have relapsed so far. Median response duration is 29+ months and the median survival is 48+ months. The survival rate is 69% in the first year and 66% in the second year. A total of 152 cycles were evaluated for toxicity. Major hematological toxicity was myelosuppression and neutropenia, detected in 50.65%, was mostly grades 1-2. Neutropenic fever occurred in only 11 cycles. The side effects of the consolidation therapy were also acceptable. We conclude that the VB-CHEP regimen with consolidation therapy for high-risk patients may be an effective treatment for advanced stage aggressive NHL.

The place of occupational therapy in rehabilitation strategies of complex regional pain syndrome: Comparative study of 60 cases.

PubMed

Rome, L

2016-10-01

The purpose of the study was to assess the value of combining occupational therapy (OT) with physical therapy (PT) for the rehabilitation of complex regional pain syndrome (CRPS) and to measure its effectiveness on activities of daily life. Sixty patients with CRPS type 1 were recruited and interviewed between September 1, 2014 and February 1, 2015. Thirty patients had undergone PT and thirty had undergone PT+OT. They were administered the short-form of the "Assessment of Life Habits" questionnaire (v.3.0 LIFE-H) created in Canada. This questionnaire consists of 16 items exploring activities of daily living, which were used to compare the effectiveness of the two rehabilitation protocols. The results of each test were submitted to the Wilcoxon test. After confirming the complexity of CRPS in terms of its etiology, clinical signs and progression, rehabilitation was effective, especially for pain. The patients who received PT+OT had on average 10% better dressing and undressing function, 25% better for meal preparation, and 20% better on personal care than those who underwent PT only. In CRPS, OT combined with PT brings a real benefit in restoring the essential activities of daily life. This strategy could be implemented as soon the diagnosis confirmed and continued for a very long time. It helps to avoid the risk of dependence on third parties. Copyright © 2016 SFCM. Published by Elsevier Masson SAS. All rights reserved.

Establishing a stem cell culture laboratory for clinical trials

PubMed Central

Sekiya, Elíseo Joji; Forte, Andresa; Kühn, Telma Ingrid Borges de Bellis; Janz, Felipe; Bydlowski, Sérgio Paulo; Alves, Adelson

2012-01-01

Adult stem/progenitor cells are found in different human tissues. An in vitro cell culture is needed for their isolation or for their expansion when they are not available in a sufficient quantity to regenerate damaged organs and tissues. The level of complexity of these new technologies requires adequate facilities, qualified personnel with experience in cell culture techniques, assessment of quality and clear protocols for cell production. The rules for the implementation of cell therapy centers involve national and international standards of good manufacturing practices. However, such standards are not uniform, reflecting the diversity of technical and scientific development. Here standards from the United States, the European Union and Brazil are analyzed. Moreover, practical solutions encountered for the implementation of a cell therapy center appropriate for the preparation and supply of cultured cells for clinical studies are described. Development stages involved the planning and preparation of the project, the construction of the facility, standardization of laboratory procedures and development of systems to prevent cross contamination. Combining the theoretical knowledge of research centers involved in the study of cells with the practical experience of blood therapy services that manage structures for cell transplantation is presented as the best potential for synergy to meet the demands to implement cell therapy centers. PMID:23049427

A Phase II Study of Intensity Modulated Radiation Therapy to the Pelvis for Postoperative Patients With Endometrial Carcinoma: Radiation Therapy Oncology Group Trial 0418

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

Jhingran, Anuja, E-mail: ajhingra@mdanderson.org; Winter, Kathryn; Portelance, Lorraine

2012-09-01

Purpose: To determine the feasibility of pelvic intensity modulated radiation therapy (IMRT) for patients with endometrial cancer in a multi-institutional setting and to determine whether this treatment is associated with fewer short-term bowel adverse events than standard radiation therapy. Methods: Patients with adenocarcinoma of the endometrium treated with pelvic radiation therapy alone were eligible. Guidelines for target definition and delineation, dose prescription, and dose-volume constraints for the targets and critical normal structures were detailed in the study protocol and a web-based atlas. Results: Fifty-eight patients were accrued by 25 institutions; 43 were eligible for analysis. Forty-two patients (98%) had anmore » acceptable IMRT plan; 1 had an unacceptable variation from the prescribed dose to the nodal planning target volume. The proportions of cases in which doses to critical normal structures exceeded protocol criteria were as follows: bladder, 67%; rectum, 76%; bowel, 17%; and femoral heads, 33%. Twelve patients (28%) developed grade {>=}2 short-term bowel adverse events. Conclusions: Pelvic IMRT for endometrial cancer is feasible across multiple institutions with use of a detailed protocol and centralized quality assurance (QA). For future trials, contouring of vaginal and nodal tissue will need continued monitoring with good QA and better definitions will be needed for organs at risk.« less

Oral hygiene in patients with oral cancer undergoing chemotherapy and/or radiotherapy after prosthesis rehabilitation: protocol proposal.

PubMed

Rapone, B; Nardi, G M; DI Venere, D; Pettini, F; Grassi, F R; Corsalini, M

2016-01-01

This study was aimed at assessing the effectiveness and the importance of an oral hygiene (OH) protocol in patients undergoing radiation therapy and chemotherapy after prosthesis rehabilitation, in order to reduce or minimize oral complications. This study was carried out at the Department of Dental Science, at the University of Bari-Italy from December 2012 to December 2015 on 34 selected patients with primary oral cancer undergoing chemotherapy and radiotherapy after prosthesis rehabilitation. They were divided into 2 groups according to their age, sex and cancer therapy. Seventeen patients were assigned to the control group and seventeen in the experimental one. In the experimental group (Table 1), patients underwent an oral hygiene protocol whereas in the control group (Table 2) patients received the usual care provided within the clinical setting. All the patients gave written informed consent. It has been asked and obtained the authorisation from the Ethics Committee of the Dental Science and Surgery Department. Results show that in patients undergoing the oral hygiene protocol, the complications and the risks of infection and permanent dental problems have been minimized. Indeed, of the seventeen patients undergoing the OH protocol, 70% obtained positive results and were satisfied with the program outcome. The role of the health care providers is essential to educate patients to adhere to the prescribed treatments and reinforce their motivation in oral hygiene. The oral hygiene procedures prevent and ameliorate oral complications due to the radiation therapy and chemotherapy.

Development of a cross-disciplinary continuous insulin infusion protocol for non-critically ill patients in a French university hospital.

PubMed

Bernard, Lise; Roche, Béatrice; Batisse, Marie; Maqdasy, Salwan; Terral, Daniel; Sautou, Valérie; Tauveron, Igor

2016-10-01

In non-critically ill patients, the use of an insulin syringe pump allows the management of temporary situations during which other therapies cannot be used (failure of subcutaneous injections, awaiting advice from the diabetes team, emergency situations, prolonged corticosteroid therapy, initiation of an artificial nutrition, need for a fasting status, etc.). To manage the risks related to this «never event», the use of a standard validated protocol for insulin administration and monitoring is an essential prerequisite. To this end, a multidisciplinary approach is recommended. With the support of our subcommission «Endocrinology-Diabetology», we proceeded with a «step-by-step process» to create such a standardized protocol: (1) review of all existing protocols in our hospital; (2) overview of the literature data concerning insulin infusion protocols developed by multidisciplinary teams in France and abroad; (3) development of a standardized protocol for non-intensive care unit patients, respecting the current recommendations and adapting it to the working habits of health teams; and (4) validation of the protocol Two protocols based on the same structure but adapted to the health status of the patient have been developed. The protocols are divided in to three parts: (1) golden rules to make the use of the protocol appropriate and safe; (2) the algorithm (a double entry table) corresponding to a dynamic adaptation of insulin doses, clearly defining the target and the 'at risk situations'; and (3) practical aspects of the protocol: preparation of the syringe, treatment initiation and traceability. The protocols have been validated by the institution. Our standardized insulin infusion protocol is simple, easy to implement, safe and is likely to be applicable in diverse care units. However, the efficiency, safety and the workability of our protocols have to be clinically evaluated. © 2016 John Wiley & Sons, Ltd.

Evaluation of the effectiveness of robotic gait training and gait-focused physical therapy programs for children and youth with cerebral palsy: a mixed methods RCT.

PubMed

Wiart, Lesley; Rosychuk, Rhonda J; Wright, F Virginia

2016-06-02

Robot assisted gait training (RAGT) is considered to be a promising approach for improving gait-related gross motor function of children and youth with cerebral palsy. However, RAGT has yet to be empirically demonstrated to be effective. This knowledge gap is particularly salient given the strong interest in this intensive therapy, the high cost of the technology, and the requirement for specialized rehabilitation centre resources. This is a research protocol describing a prospective, multi-centre, concurrent mixed methods study comprised of a randomized controlled trial (RCT) and an interpretive descriptive qualitative design. It is a mixed methods study designed to determine the relative effectiveness of three physical therapy treatment conditions (i.e., RAGT, a functional physical therapy program conducted over-ground (fPT), and RAGT + fPT) on gait related motor skills of ambulatory children with cerebral palsy. Children with cerebral palsy aged 5-18 years who are ambulatory (Gross Motor Function Classification System Levels II and III) will be randomly allocated to one of four treatment conditions: 1) RAGT, 2) fPT, 3) RAGT and fPT combined, or 4) a maintenance therapy only control group. The qualitative component will explicate child and parent experiences with the interventions, provide insight into the values that underlie their therapy goals, and assist with interpretation of the results of the RCT. n/a. NCT02391324 Registered March 12, 2015.

Virtual reality exposure in the treatment of fear of flying.

PubMed

da Costa, Rafael T; Sardinha, Aline; Nardi, Antonio E

2008-09-01

Recently, a growing body of research has appeared on different aspects of virtual reality exposure (VRE) therapy applied to the treatment of anxiety disorders. The purpose of this article was to review with a systematic methodology the evidences that support the potential effectiveness of this therapy in the treatment of fear of flying (FOF), a problem that significantly affects patients' social functioning and personal welfare. Potential studies were identified via computerized search using the PubMed/Medline and Web of Science databases, and additional review of their references. Articles ranged from 1969 to 2007 and the keywords used in the search were: "virtual reality" and "fear of flying"; "virtual reality" and "flying phobia"; or "virtual reality" and "flight phobia." There were 40 studies using VRE in the treatment of FOF identified, mostly on the effectiveness of VRE therapy in group and case studies. Several components of the treatment protocols differed among the studies, which made the results comparison a challenging task. Nevertheless, controlled studies demonstrate that VRE treatment is effective with or without cognitive behavior therapy (CBT) and/or psychoeducation and that it is considered to be an effective component of the treatment of FOF. All studies that used cognitive and relaxation techniques in addition to VRE treatment were effective. More randomized clinical trials are required in which VRE therapy could be compared with standard exposure therapy. Thus, we suggest that CBT, psychoeducation, and VRE could be combined to treat FOF.

Manualized therapy for PTSD: flexing the structure of cognitive processing therapy.

PubMed

Galovski, Tara E; Blain, Leah M; Mott, Juliette M; Elwood, Lisa; Houle, Timothy

2012-12-01

This study tested a modified cognitive processing therapy (MCPT) intervention designed as a more flexible administration of the protocol. Number of sessions was determined by client progress toward a priori defined end-state criteria, "stressor sessions" were inserted when necessary, and therapy was conducted by novice CPT clinicians. A randomized, controlled, repeated measures, semicrossover design was utilized (a) to test the relative efficacy of the MCPT intervention compared with a symptom-monitoring delayed treatment (SMDT) condition and (b) to assess within-group variation in change with a sample of 100 male and female interpersonal trauma survivors with posttraumatic stress disorder (PTSD). Hierarchical linear modeling analyses revealed that MCPT evidenced greater improvement on all primary (PTSD and depression) and secondary (guilt, quality of life, general mental health, social functioning, and health perceptions) outcomes compared with SMDT. After the conclusion of SMDT, participants crossed over to MCPT, resulting in a combined MCPT sample (n = 69). Of the 50 participants who completed MCPT, 58% reached end-state criteria prior to the 12th session, 8% at Session 12, and 34% between Sessions 12 and 18. Maintenance of treatment gains was found at the 3-month follow-up, with only 2 of the treated sample meeting criteria for PTSD. Use of stressor sessions did not result in poorer treatment outcomes. Findings suggest that individuals respond at a variable rate to CPT, with significant benefit from additional therapy when indicated and excellent maintenance of gains. Insertion of stressor sessions did not alter the efficacy of the therapy.

The impact of ex vivo clinical grade activation protocols on human T-cell phenotype and function for the generation of genetically modified cells for adoptive cell transfer therapy.

PubMed

Tumeh, Paul C; Koya, Richard C; Chodon, Thinle; Graham, Nicholas A; Graeber, Thomas G; Comin-Anduix, Begoña; Ribas, Antoni

2010-10-01

Optimized conditions for the ex vivo activation, genetic manipulation, and expansion of human lymphocytes for adoptive cell therapy may lead to protocols that maximize their in vivo function. We analyzed the effects of 4 clinical grade activation and expansion protocols over 3 weeks on cell proliferative rate, immunophenotype, cell metabolism, and transduction efficiency of human peripheral blood mononuclear cells (PBMCs). Peak lentiviral transduction efficiency was early (days 2 to 4), at a time when cells showed a larger size, maximal uptake of metabolic substrates, and the highest level of proximal T-cell receptor signaling engagement. Anti-CD2/3/28 activation beads induced greater proliferation rate and skewed PBMCs early on to a CD4 phenotype when compared with the cells cultured in OKT3. Multicolor surface phenotyping demonstrated that changes in T-cell surface markers that define T-cell functional phenotypes were dependent on the time spent in culture as opposed to the particular activation protocol. In conclusion, ex vivo activation of human PBMCs for adoptive cell therapy demonstrate defined immunophenotypic and functional signatures over time, with cells early on showing larger sizes, higher transduction efficiency, maximal metabolic activity, and zeta-chain-associated protein-70 activation.

Inhaled nitric oxide, oxygen, and alkalosis: dose-response interactions in a lamb model of pulmonary hypertension.

PubMed

Heidersbach, R S; Johengen, M J; Bekker, J M; Fineman, J R

1999-07-01

Inhaled nitric oxide (NO) is currently used as an adjuvant therapy for a variety of pulmonary hypertensive disorders. In both animal and human studies, inhaled NO induces selective, dose-dependent pulmonary vasodilation. However, its potential interactions with other simultaneously used pulmonary vasodilator therapies have not been studied. Therefore, the objective of this study was to determine the potential dose-response interactions of inhaled NO, oxygen, and alkalosis therapies. Fourteen newborn lambs (age 1-6 days) were instrumented to measure vascular pressures and left pulmonary artery blood flow. After recovery, the lambs were sedated and mechanically ventilated. During steady-state pulmonary hypertension induced by U46619 (a thromboxane A2 mimic), the lambs were exposed to the following conditions: Protocol A, inhaled NO (0, 5, 40, and 80 ppm) and inspired oxygen concentrations (FiO2) of 0.21, 0.50, and 1.00; and Protocol B, inhaled NO (0, 5, 40, and 80 ppm) and arterial pH levels of 7.30, 7.40, 7.50, and 7.60. Each condition (in randomly chosen order) was maintained for 10 min, and all variables were allowed to return to baseline between conditions. Inhaled NO, oxygen, and alkalosis produced dose-dependent decreases in mean pulmonary arterial pressures (P < 0.05). Systemic arterial pressure remained unchanged. At 5 ppm of inhaled NO, alkalosis and oxygen induced further dose-dependent decreases in mean pulmonary arterial pressures (P < 0.05). At inhaled NO doses > 5 ppm, alkalosis induced further dose-independent decreases in mean pulmonary arterial pressure, while oxygen did not. We conclude that in this animal model, oxygen, alkalosis, and inhaled NO induced selective, dose-dependent pulmonary vasodilation. However, when combined, a systemic arterial pH > 7.40 augmented inhaled NO-induced pulmonary vasodilation, while an FiO2 > 0.5 did not. Therefore, weaning high FiO2 during inhaled NO therapy should be considered, since it may not diminish the pulmonary vasodilating effects. Further studies are warranted to guide the clinical weaning strategies of these pulmonary vasodilator therapies.

Influence of Noncompliance With Radiation Therapy Protocol Guidelines and Operative Bed Recurrences for Children With Rhabdomyosarcoma and Microscopic Residual Disease: A Report From the Children's Oncology Group

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

Million, Lynn, E-mail: lynn.million@hci.utah.ed; Anderson, James; Breneman, John

2011-06-01

Purpose: Postoperative radiation therapy (RT) is recommended for patients with rhabdomyosarcoma having microscopic disease. Sometimes RT dose/volume is reduced or omitted in an attempt to avoid late effects, particularly in young children. We reviewed operative bed recurrences to determine if noncompliance with RT protocol guidelines influenced local-regional control. Methods and Materials: All operative bed recurrences among 695 Group II rhabdomyosarcoma patients in Intergroup Rhabdomyosarcoma Study Group (IRS) I through IV were reviewed for deviation from RT protocol. Major/minor dose deviation was defined as >10% or 6-10% of the prescribed dose (40-60 Gy), respectively. Major/minor volume deviation was defined as tumormore » excluded from the RT field or treatment volume not covered by the specified margin (preoperative tumor volume and 2- to 5-cm margin), respectively. No RT was a major deviation. Results: Forty-six of 83 (55%) patients with operative bed recurrences did not receive the intended RT (39 major and 7 minor deviations). RT omission was the most frequent RT protocol deviation (19/46, 41%), followed by dose (17/46, 37%), volume (9/46, 20%), and dose and volume deviation (1/46, 2%). Only 7 operative bed recurrences occurred in IRS IV (5% local-regional failure) with only 3 RT protocol deviations. Sixty-three (76%) patients with recurrence died of disease despite retrieval therapy, including 13 of 19 nonirradiated children. Conclusion: Over half of the operative bed recurrences were associated with noncompliance; omission of RT was the most common protocol deviation. Three fourths of children die when local-regional disease is not controlled, emphasizing the importance of RT in Group II rhabdomyosarcoma.« less

A nurse-guided, basal-prandial insulin treatment protocol for achieving glycaemic control of hospitalized, non-critically ill diabetes patients, is non-inferior to physician-guided therapy: A pivotal, nurse-empowerment study.

PubMed

Segal, Gad; Karniel, Eli; Mahagna, Ahmed; Kaa'dan, Fadi; Levi, Zehava; Balik, Chaya

2015-12-01

Basal-prandial insulin is established for glycaemic control for hospitalized, type 2 diabetes patients. Empowering nurses to guide such protocols could be advantageous.The study aims to comparatively assess the efficacy and safety of glycaemic control by a nurse-guided protocol with physician-guided therapy. It also aims to assess the impact of empowerment on the nurses' sense of competence. This is a prospective, controlled, randomized, single-blinded study. Validated protocol utilizing basal-prandial insulin was used. Glycaemic control was the primary efficacy outcome, whereas hypoglycaemia and laboratory parameters were followed for safety. Assessment of nurses' psychological empowerment was done. One hundred fifty-eight treatment days of 53 patients were included. Patients were randomized to either study group (n = 27) or control group (n = 26). Glycaemia deviation from liberal range (60-300 mg/dL) was 7.4% of days for nurse-guided, basal-prandial insulin treatment protocol (NGP) and 7.84% for physician-guided therapy (PGT), P = 0.901. Rate of glycaemia deviation from the strict range (100-180 mg/dL) was 49.76% for NGP and 47.38% for PGT, P = 0.703. Mean range of daily deviation was similar (77.05 mg/dL for NGP and 76.04 mg/dL for PGT, P = 0.93). There were no significant differences in safety parameters. An empowerment questionnaire showed tendency for increased nurses' sense of competence. Nurse-guided protocol is non-inferior to physician-guided treatment in efficacy and safety parameters. Nurses' sense of competence was positively influenced. © 2014 Wiley Publishing Asia Pty Ltd.

The effects of sign language on spoken language acquisition in children with hearing loss: a systematic review protocol.

PubMed

Fitzpatrick, Elizabeth M; Stevens, Adrienne; Garritty, Chantelle; Moher, David

2013-12-06

Permanent childhood hearing loss affects 1 to 3 per 1000 children and frequently disrupts typical spoken language acquisition. Early identification of hearing loss through universal newborn hearing screening and the use of new hearing technologies including cochlear implants make spoken language an option for most children. However, there is no consensus on what constitutes optimal interventions for children when spoken language is the desired outcome. Intervention and educational approaches ranging from oral language only to oral language combined with various forms of sign language have evolved. Parents are therefore faced with important decisions in the first months of their child's life. This article presents the protocol for a systematic review of the effects of using sign language in combination with oral language intervention on spoken language acquisition. Studies addressing early intervention will be selected in which therapy involving oral language intervention and any form of sign language or sign support is used. Comparison groups will include children in early oral language intervention programs without sign support. The primary outcomes of interest to be examined include all measures of auditory, vocabulary, language, speech production, and speech intelligibility skills. We will include randomized controlled trials, controlled clinical trials, and other quasi-experimental designs that include comparator groups as well as prospective and retrospective cohort studies. Case-control, cross-sectional, case series, and case studies will be excluded. Several electronic databases will be searched (for example, MEDLINE, EMBASE, CINAHL, PsycINFO) as well as grey literature and key websites. We anticipate that a narrative synthesis of the evidence will be required. We will carry out meta-analysis for outcomes if clinical similarity, quantity and quality permit quantitative pooling of data. We will conduct subgroup analyses if possible according to severity/type of hearing disorder, age of identification, and type of hearing technology. This review will provide evidence on the effectiveness of using sign language in combination with oral language therapies for developing spoken language in children with hearing loss who are identified at a young age. The information from this review can provide guidance to parents and intervention specialists, inform policy decisions and provide directions for future research. CRD42013005426.

Patient and provider interventions for managing osteoarthritis in primary care: protocols for two randomized controlled trials

PubMed Central

2012-01-01

Background Osteoarthritis (OA) of the hip and knee are among the most common chronic conditions, resulting in substantial pain and functional limitations. Adequate management of OA requires a combination of medical and behavioral strategies. However, some recommended therapies are under-utilized in clinical settings, and the majority of patients with hip and knee OA are overweight and physically inactive. Consequently, interventions at the provider-level and patient-level both have potential for improving outcomes. This manuscript describes two ongoing randomized clinical trials being conducted in two different health care systems, examining patient-based and provider-based interventions for managing hip and knee OA in primary care. Methods / Design One study is being conducted within the Department of Veterans Affairs (VA) health care system and will compare a Combined Patient and Provider intervention relative to usual care among n = 300 patients (10 from each of 30 primary care providers). Another study is being conducted within the Duke Primary Care Research Consortium and will compare Patient Only, Provider Only, and Combined (Patient + Provider) interventions relative to usual care among n = 560 patients across 10 clinics. Participants in these studies have clinical and / or radiographic evidence of hip or knee osteoarthritis, are overweight, and do not meet current physical activity guidelines. The 12-month, telephone-based patient intervention focuses on physical activity, weight management, and cognitive behavioral pain management. The provider intervention involves provision of patient-specific recommendations for care (e.g., referral to physical therapy, knee brace, joint injection), based on evidence-based guidelines. Outcomes are collected at baseline, 6-months, and 12-months. The primary outcome is the Western Ontario and McMasters Universities Osteoarthritis Index (self-reported pain, stiffness, and function), and secondary outcomes are the Short Physical Performance Test Protocol (objective physical function) and the Patient Health Questionnaire-8 (depressive symptoms). Cost effectiveness of the interventions will also be assessed. Discussion Results of these two studies will further our understanding of the most effective strategies for improving hip and knee OA outcomes in primary care settings. Trial registration NCT01130740 (VA); NCT 01435109 (NIH) PMID:22530979

A Phase III Study of Conventional Radiation Therapy Plus Thalidomide Versus Conventional Radiation Therapy for Multiple Brain Metastases (RTOG 0118)

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

Knisely, Jonathan P.S.; Berkey, Brian; Chakravarti, Arnab

2008-05-01

Purpose: To compare whole-brain radiation therapy (WBRT) with WBRT combined with thalidomide for patients with brain metastases not amenable to resection or radiosurgery. Patients and Methods: Patients with Zubrod performance status 0-1, MRI-documented multiple (>3), large (>4 cm), or midbrain brain metastases arising from a histopathologically confirmed extracranial primary tumor, and an anticipated survival of >8 weeks were randomized to receive WBRT to a dose of 37.5 Gy in 15 fractions with or without thalidomide during and after WBRT. Prerandomization stratification used Radiation Therapy Oncology Group (RTOG) Recursive Partitioning Analysis (RPA) Class and whether post-WBRT chemotherapy was planned. Endpoints includedmore » overall survival, progression-free survival, time to neurocognitive progression, the cause of death, toxicities, and quality of life. A protocol-planned interim analysis documented that the trial had an extremely low probability of ever showing a significant difference favoring the thalidomide arm given the results at the time of the analysis, and it was therefore closed on the basis of predefined statistical guidelines. Results: Enrolled in the study were 332 patients. Of 183 accrued patients, 93 were randomized to receive WBRT alone and 90 to WBRT and thalidomide. Median survival was 3.9 months for both arms. No novel toxicities were seen, but thalidomide was not well tolerated in this population. Forty-eight percent of patients discontinued thalidomide because of side effects. Conclusion: Thalidomide provided no survival benefit for patients with multiple, large, or midbrain metastases when combined with WBRT; nearly half the patients discontinued thalidomide due to side effects.« less

Manual therapy in joint and nerve structures combined with exercises in the treatment of recurrent ankle sprains: A randomized, controlled trial.

PubMed

Plaza-Manzano, Gustavo; Vergara-Vila, Marta; Val-Otero, Sandra; Rivera-Prieto, Cristina; Pecos-Martin, Daniel; Gallego-Izquierdo, Tomás; Ferragut-Garcías, Alejandro; Romero-Franco, Natalia

2016-12-01

Recurrent ankle sprains often involve residual symptoms for which subjects often perform proprioceptive or/and strengthening exercises. However, the effectiveness of mobilization to influence important nerve structures due to its anatomical distribution like tibial and peroneal nerves is unclear. To analyze the effects of proprioceptive/strengthening exercises versus the same exercises and manual therapy including mobilizations to influence joint and nerve structures in the management of recurrent ankle sprains. A randomized single-blind controlled clinical trial. Fifty-six patients with recurrent ankle sprains and regular sports practice were randomly assigned to experimental or control group. The control group performed 4 weeks of proprioceptive/strengthening exercises; the experimental group performed 4 weeks of the same exercises combined with manual therapy (mobilizations to influence joint and nerve structures). Pain, self-reported functional ankle instability, pressure pain threshold (PPT), ankle muscle strength, and active range of motion (ROM) were evaluated in the ankle joint before, just after and one month after the interventions. The within-group differences revealed improvements in all of the variables in both groups throughout the time. Between-group differences revealed that the experimental group exhibited lower pain levels and self-reported functional ankle instability and higher PPT, ankle muscle strength and ROM values compared to the control group immediately after the interventions and one month later. A protocol involving proprioceptive and strengthening exercises and manual therapy (mobilizations to influence joint and nerve structures) resulted in greater improvements in pain, self-reported functional joint stability, strength and ROM compared to exercises alone. Copyright © 2016 Elsevier Ltd. All rights reserved.

Large-area burns with pandrug-resistant Pseudomonas aeruginosa infection and respiratory failure.

PubMed

Ning, Fang-Gang; Zhao, Xiao-Zhuo; Bian, Jing; Zhang, Guo-An

2011-02-01

Infection due to pandrug-resistant Pseudomonas aeruginosa (PDRPA) has become a challenge in clinical practice. The aim of this research was to summarize the treatment of large-area burns (60% - 80%) with PDRPA infection and respiratory failure in our hospital over the last two years, and to explore a feasible treatment protocol for such patients. We retrospectively analyzed the treatment of five patients with large-area burns accompanied by PDRPA infection and respiratory failure transferred to our hospital from burn units in hospitals in other Chinese cities from January 2008 to February 2010. Before PDRPA infection occurred, all five patients had open wounds with large areas of granulation because of the failure of surgery and dissolving of scar tissue; they had also undergone long-term administration of carbapenems. This therapy included ventilatory support, rigorous repair of wounds, and combined antibiotic therapy targeted at drug-resistance mechanisms, including carbapenems, ciprofloxacin, macrolide antibiotics and β-lactamase inhibitors. Four patients recovered from burns and one died after therapy. First, compromised immunity caused by delayed healing of burn wounds in patients with large-area burns and long-term administration of carbapenems may be the important factors in the initiation and progression of PDRPA infection. Second, if targeted at drug-resistance mechanisms, combined antibiotic therapy using carbapenems, ciprofloxacin, macrolide antibiotics and β-lactamase inhibitors could effectively control PDRPA infection. Third, although patients with large-area burns suffered respiratory failure and had high risks from anesthesia and surgery, only aggressive skin grafting with ventilatory support could control the infection and save lives. Patients may not be able to tolerate a long surgical procedure, so the duration of surgery should be minimized, and the frequency of surgery increased.

A generative model for segmentation of tumor and organs-at-risk for radiation therapy planning of glioblastoma patients

NASA Astrophysics Data System (ADS)

Agn, Mikael; Law, Ian; Munck af Rosenschöld, Per; Van Leemput, Koen

2016-03-01

We present a fully automated generative method for simultaneous brain tumor and organs-at-risk segmentation in multi-modal magnetic resonance images. The method combines an existing whole-brain segmentation technique with a spatial tumor prior, which uses convolutional restricted Boltzmann machines to model tumor shape. The method is not tuned to any specific imaging protocol and can simultaneously segment the gross tumor volume, peritumoral edema and healthy tissue structures relevant for radiotherapy planning. We validate the method on a manually delineated clinical data set of glioblastoma patients by comparing segmentations of gross tumor volume, brainstem and hippocampus. The preliminary results demonstrate the feasibility of the method.

Acute Effect of Different Combined Stretching Methods on Acceleration and Speed in Soccer Players.

PubMed

Amiri-Khorasani, Mohammadtaghi; Calleja-Gonzalez, Julio; Mogharabi-Manzari, Mansooreh

2016-04-01

The purpose of this study was to investigate the acute effect of different stretching methods, during a warm-up, on the acceleration and speed of soccer players. The acceleration performance of 20 collegiate soccer players (body height: 177.25 ± 5.31 cm; body mass: 65.10 ± 5.62 kg; age: 16.85 ± 0.87 years; BMI: 20.70 ± 5.54; experience: 8.46 ± 1.49 years) was evaluated after different warm-up procedures, using 10 and 20 m tests. Subjects performed five types of a warm-up: static, dynamic, combined static + dynamic, combined dynamic + static, and no-stretching. Subjects were divided into five groups. Each group performed five different warm-up protocols in five non-consecutive days. The warm-up protocol used for each group was randomly assigned. The protocols consisted of 4 min jogging, a 1 min stretching program (except for the no-stretching protocol), and 2 min rest periods, followed by the 10 and 20 m sprint test, on the same day. The current findings showed significant differences in the 10 and 20 m tests after dynamic stretching compared with static, combined, and no-stretching protocols. There were also significant differences between the combined stretching compared with static and no-stretching protocols. We concluded that soccer players performed better with respect to acceleration and speed, after dynamic and combined stretching, as they were able to produce more force for a faster execution.

Occupational Therapy and Sensory Integration for Children with Autism: A Feasibility, Safety, Acceptability and Fidelity Study

ERIC Educational Resources Information Center

Schaaf, Roseann C.; Benevides, Teal W.; Kelly, Donna; Mailloux-Maggio, Zoe

2012-01-01

Objective: To examine the feasibility, safety, and acceptability of a manualized protocol of occupational therapy using sensory integration principles for children with autism. Methods: Ten children diagnosed with autism spectrum disorder ages 4-8 years received intensive occupational therapy intervention using sensory integration principles…

A Short Term Therapy Approach to Processing Trauma: Art Therapy and Bilateral Stimulation

ERIC Educational Resources Information Center

Tripp, Tally

2007-01-01

This article describes a dynamic, short-term art therapy approach that has been developed for the treatment of trauma related disorders. Using a modified Eye Movement Desensitization and Reprocessing (EMDR) protocol with alternating tactile and auditory bilateral stimulation, associations are rapidly brought to conscious awareness and expressed in…

Phonological outcome of laryngeal framework surgery by different anesthesia protocols: a single-surgeon experience.

PubMed

Kanazawa, Takeharu; Watanabe, Yusuke; Komazawa, Daigo; Indo, Kanako; Misawa, Kiyoshi; Nagatomo, Takafumi; Shimada, Mari; Iino, Yukiko; Ichimura, Keiichi

2014-02-01

Similar to combined arytenoid adduction and medialization laryngoplasty (i.e. combined surgery) under local anesthesia, general anesthesia by intubation or by the laryngeal mask airway (LMA) method significantly improves phonological outcome. Thus, laryngeal framework surgery under general anesthesia is a promising surgical approach for selected patients with unilateral vocal cord paralysis (UVCP). The advantages of laryngeal framework surgery under local anesthesia have been described, but no studies exist concerning the difference in phonological outcome of laryngeal framework surgery performed under general anesthesia. To add new information, we retrospectively investigated the phonological outcome of the combined surgery performed under three different anesthesia protocols. Thirty-nine consecutive patients with severe UVCP underwent the combined surgery under three anesthesia protocols performed by a single surgeon: (1) under general anesthesia by intubation, (2) under general anesthesia using LMA, and (3) under local anesthesia. Under all anesthesia protocols, the vocal cords of most patients could be positioned such that the best vocal outcome could be expected. Statistical analyses demonstrated improved maximum phonation time and mean airflow rate, and grade, roughness, breathiness, asthenia, and strain (GRBAS) scale in all patients, regardless of their anesthesia protocol. Furthermore, of the three protocols, local anesthesia had the shortest operation time.

Nonpainful wide-area compression inhibits experimental pain

PubMed Central

Honigman, Liat; Bar-Bachar, Ofrit; Yarnitsky, David; Sprecher, Elliot; Granovsky, Yelena

2016-01-01

Abstract Compression therapy, a well-recognized treatment for lymphoedema and venous disorders, pressurizes limbs and generates massive non-noxious afferent sensory barrages. The aim of this study was to study whether such afferent activity has an analgesic effect when applied on the lower limbs, hypothesizing that larger compression areas will induce stronger analgesic effects, and whether this effect correlates with conditioned pain modulation (CPM). Thirty young healthy subjects received painful heat and pressure stimuli (47°C for 30 seconds, forearm; 300 kPa for 15 seconds, wrist) before and during 3 compression protocols of either SMALL (up to ankles), MEDIUM (up to knees), or LARGE (up to hips) compression areas. Conditioned pain modulation (heat pain conditioned by noxious cold water) was tested before and after each compression protocol. The LARGE protocol induced more analgesia for heat than the SMALL protocol (P < 0.001). The analgesic effect interacted with gender (P = 0.015). The LARGE protocol was more efficient for females, whereas the MEDIUM protocol was more efficient for males. Pressure pain was reduced by all protocols (P < 0.001) with no differences between protocols and no gender effect. Conditioned pain modulation was more efficient than the compression-induced analgesia. For the LARGE protocol, precompression CPM efficiency positively correlated with compression-induced analgesia. Large body area compression exerts an area-dependent analgesic effect on experimental pain stimuli. The observed correlation with pain inhibition in response to robust non-noxious sensory stimulation may suggest that compression therapy shares similar mechanisms with inhibitory pain modulation assessed through CPM. PMID:27152691

Movement towards transdiagnostic psychotherapeutic practices for the affective disorders.

PubMed

Gros, Daniel F; Allan, Nicholas P; Szafranski, Derek D

2016-08-01

Evidence-based cognitive behavioural therapy (CBT) practices were first developed in the 1960s. Over the decades, refinements and alternative symptom foci resulted in the development of several CBT protocols/manuals for each of the many disorders, especially in the affective disorders. Although shown to be effective in highly trained providers, the proliferation of CBT protocols also has shown to demonstrate challenges in dissemination and implementation efforts due to the sheer number of CBT protocols and their related training requirements (eg, 6 months per protocol) and their related cost (eg, over US$2000 each; lost days/hours at work). To address these concerns, newer transdiagnostic CBT protocols have been developed to reduce the number of disorder-specific CBT protocols needed to treat patients with affective disorders. Transdiagnostic treatments are based on the notion that various disorder-specific CBT protocols contain important but overlapping treatment components that can be distilled into a single treatment and therefore address the symptoms and comorbidities across all of the disorders at once. 3 examples of transdiagnostic treatments include group CBT of anxiety, unified protocol for transdiagnostic treatment for emotional disorders and transdiagnostic behaviour therapy. Each transdiagnostic protocol is designed for a different set of disorders, contains a varied amount of CBT treatment components and is tested in different types of samples. However, together, these 3 transdiagnostic psychotherapies represent the future of CBT practice. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Development of a Multileaf Collimator for Proton Radiotherapy

DTIC Science & Technology

2007-06-01

for proton radiotherapy, and the first year of the project to develop image guided treatment protocols for proton therapy . This research...multileaf collimator (MLC) for proton therapy and investigates the issues that must be resolved to use an MLC in proton therapy . The second technology...the contract included three development agreements directly related to the work supported by this grant to develop technology for proton therapy .

Music therapy protocol development to enhance swallowing training for stroke patients with dysphagia.

PubMed

Kim, Soo Ji

2010-01-01

Considering the devastating condition of dysphagia, it is necessary to provide intensive therapeutic regimen based on interdisciplinary approach. In this aspect, music-enhanced swallowing protocol was developed through a pilot study. Then, the modified protocol from a pilot study was examined with 8 stroke patients in a local hospital. The protocol was designed to improve oral motor control, laryngeal elevation, breathing, and swallowing functions. The dependent variables measured included reflex, respiration, and laryngeal functions using the Frenchay Dysarthria assessment. Results from the initial to the midevaluation showed that pitch in the laryngeal category were statistically significant after 6th sessions. After the 12th session, when the final evaluation was compared with the initial assessment, additional categories revealed statistically significant changes. It is recommended that this study should be replicated with a control group and a larger sample using either FEES or video fluoroscopy for scientific data to further substantiate music therapy outcomes in stroke rehabilitation.

Gene Therapy for Bone Defects in Oral and Maxillofacial Surgery: A Systematic Review and Meta-Analysis of Animal Studies.

PubMed

Fliefel, Riham; Kühnisch, Jan; Ehrenfeld, Michael; Otto, Sven

2017-02-15

Craniofacial bone defects are challenging problems for maxillofacial surgeons over the years. With the development of cell and molecular biology, gene therapy is a breaking new technology with the aim of regenerating tissues by acting as a delivery system for therapeutic genes in the craniofacial region rather than treating genetic disorders. A systematic review was conducted summarizing the articles reporting gene therapy in maxillofacial surgery to answer the question: Was gene therapy successfully applied to regenerate bone in the maxillofacial region? Electronic searching of online databases was performed in addition to hand searching of the references of included articles. No language or time restrictions were enforced. Meta-analysis was done to assess significant bone formation after delivery of gene material in the surgically induced maxillofacial defects. The search identified 2081 articles, of which 57 were included with 1726 animals. Bone morphogenetic proteins were commonly used proteins for gene therapy. Viral vectors were the universally used vectors. Sprague-Dawley rats were the frequently used animal model in experimental studies. The quality of the articles ranged from excellent to average. Meta-analysis results performed on 21 articles showed that defects favored bone formation by gene therapy. Funnel plot showed symmetry with the absence of publication bias. Gene therapy is on the top list of innovative strategies that developed in the last 10 years with the hope of developing a simple chair-side protocol in the near future, combining improvement of gene delivery as well as knowledge of the molecular basis of oral and maxillofacial structures.

Safety and efficacy of endovascular therapy and gamma knife surgery for brain arteriovenous malformations in China: Study protocol for an observational clinical trial.

PubMed

Jin, Hengwei; Huo, Xiaochuan; Jiang, Yuhua; Li, Xiaolong; Li, Youxiang

2017-09-01

Brain arteriovenous malformations (BAVMs) are associated with high morbidity and mortality. The treatment of BAVM remains controversial. Microinvasive treatment, including endovascular therapy and gamma knife surgery, has been the first choice in many conditions. However, the overall clinical outcome of microinvasive treatment remains unknown and a prospective trial is needed. This is a prospective, non-randomized, and multicenter observational registry clinical trial to evaluate the safety and efficacy of microinvasive treatment for BAVMs. The study will require up to 400 patients in approximately 12 or more centers in China, followed for 2 years. Main subjects of this study are BAVM patients underwent endovascular therapy and/or gamma knife surgery. The trial will not affect the choice of treatment modality. The primary outcomes are perioperative complications (safety), and postoperative hemorrhage incidence rate and complete occlusion rate (efficacy). Secondary outcomes are elimination of hemorrhage risk factors (coexisting aneurysms and arteriovenous fistula), volume reduction and remission of symptoms. Safety and efficacy of endovascular therapy, gamma knife surgery, and various combination modes of the two modalities will be compared. Operative complications and outcomes at pretreatment, post-treatment, at discharge and at 3 months, 6 months and 2 years follow-up intervals will be analyzed using the modified Rankin Scale (mRS). The most confusion on BAVM treatment is whether to choose interventional therapy or medical therapy, and the choice of interventional therapy modes. This study will provide evidence for evaluating the safety and efficacy of microinvasive treatment in China, to characterize the microinvasive treatment strategy for BAVMs.

Management of Chronic Lateral Epicondylitis With Manual Therapy and Local Cryostimulation: A Pilot Study.

PubMed

Richer, Nadia; Marchand, Andrée-Anne; Descarreaux, Martin

2017-12-01

The purpose of this pilot study was to evaluate the feasibility and efficacy of adding cryostimulation to manual therapy in patients with chronic lateral epicondylitis. The control group (n = 19) was treated with manual therapy consisting of soft-tissue therapy and radial head mobilizations. The experimental group (n = 18) received cryostimulation in addition to manual therapy care similar to that for the control group. Both protocols consisted of 8 treatments over a 4-week period. Outcome measures included pain intensity (visual analog scale), pain-free grip strength (handheld dynamometer), and functional index (Patient-Rated Tennis Elbow Evaluation questionnaire). Assessments were performed at baseline, postintervention, and 3-month follow-up. Adherence and dropout rates were also considered. Both groups exhibited significant improvements in pain intensity and functional index at postintervention assessments, which were maintained at follow-up. All participants attended the prescribed number of treatments, but 27% were lost at follow-up. Minor adverse events were reported after cryostimulation in 4 cases. This study indicated that it is feasible to complete a clinical trial evaluating the efficacy of adding cryostimulation to manual therapy in patients with chronic lateral epicondylitis. On the basis of these preliminary data, the combination of cryostimulation and manual therapy care did not provide any additional benefits in both the short term and the long term. Manual myofascial point treatment and mobilization techniques yielded positive outcomes in chronic lateral epicondylitis. Further studies should focus on the sole therapeutic effect of cryostimulation in both patients with acute and those with chronic conditions.

Early sensory re-education of the hand after peripheral nerve repair based on mirror therapy: a randomized controlled trial.

PubMed

Paula, Mayara H; Barbosa, Rafael I; Marcolino, Alexandre M; Elui, Valéria M C; Rosén, Birgitta; Fonseca, Marisa C R

2016-01-01

Mirror therapy has been used as an alternative stimulus to feed the somatosensory cortex in an attempt to preserve hand cortical representation with better functional results. To analyze the short-term functional outcome of an early re-education program using mirror therapy compared to a late classic sensory program for hand nerve repair. This is a randomized controlled trial. We assessed 20 patients with median and ulnar nerve and flexor tendon repair using the Rosen Score combined with the DASH questionnaire. The early phase group using mirror therapy began on the first postoperative week and lasted 5 months. The control group received classic sensory re-education when the protective sensation threshold was restored. All participants received a patient education booklet and were submitted to the modified Duran protocol for flexor tendon repair. The assessments were performed by the same investigator blinded to the allocated treatment. Mann-Whitney Test and Effect Size using Cohen's d score were used for inter-group comparisons at 3 and 6 months after intervention. The primary outcome (Rosen score) values for the Mirror Therapy group and classic therapy control group after 3 and 6 months were 1.68 (SD=0.5); 1.96 (SD=0.56) and 1.65 (SD=0.52); 1.51 (SD=0.62), respectively. No between-group differences were observed. Although some clinical improvement was observed, mirror therapy was not shown to be more effective than late sensory re-education in an intermediate phase of nerve repair in the hand. Replication is needed to confirm these findings.

Feasibility, toxicity and response of upfront metaiodobenzylguanidine therapy therapy followed by German Pediatric Oncology Group Neuroblastoma 2004 protocol in newly diagnosed stage 4 neuroblastoma patients.

PubMed

Kraal, K C J M; Bleeker, G M; van Eck-Smit, B L F; van Eijkelenburg, N K A; Berthold, F; van Noesel, M M; Caron, H N; Tytgat, G A M

2017-05-01

Radiolabelled meta-iodobenzylguanidine (MIBG) is an effective option in treatment of neuroblastoma (NBL) tumours. We studied feasibility, toxicity and efficacy of upfront 131 I-MIBG and induction treatment in stage 4 NBL patients. Retrospective, multi-centre (AMC and EMC) pilot regimen (1/1/2005-2011). Newly diagnosed stage 4 NBL patients, were treated with 2 courses of 131 I-MIBG, GPOH 2004 NBL protocol, myeloablative therapy (MAT) and autologous stem cell rescue (ASCT). 131 I-MIBG was administered in a fixed dose. Response rate (RR) was defined as complete remission, very good partial response and partial response. Thirty-two patients, (median age [range] 2.9 [0-11.4] years), 21 received 131 I-MIBG therapy, 11 did not because of: MIBG non-avid (N = 5) and poor clinical condition (N = 6). In 95% of eligible patients 131 I-MIBG treatment was feasible within 2 weeks from diagnosis. Interval between chemotherapy courses was 25 days ( 131 I-MIBG group) versus 22 days (chemotherapy group). No stem cell support was needed after 131 I-MIBG therapy. Stem cell harvest in both groups was feasible, neutrophil recovery was comparable, but platelet recovery post MAT, ASCT was slower for 131 I-MIBG-treated patients. RR post 131 I-MIBG was 38%, post MAT + ASCT was 71% ( 131 I-MIBG group), 36% (chemotherapy group) and overall 59%. Induction therapy with 131 I-MIBG before the HR GPOH NB 2004 protocol is feasible, tolerable and effective in newly diagnosed stage 4 NBL patients. 131 I-MIBG upfront therapy induces early responses. Copyright © 2017 Elsevier Ltd. All rights reserved.

Current treatment options for recurrent/metastatic head and neck cancer: a post-ASCO 2011 update and review of last year's literature.

PubMed

Kurzweg, T; Möckelmann, N; Laban, S; Knecht, R

2012-10-01

The majority of patients with a squamous cell carcinoma of the head and neck present with locally advanced tumors. The first-line treatment of locally advanced tumor stages consists of a combined modality management. Despite these aggressive protocols, many patients develop locoregional recurrences or metastasis and place particularly high demands on the interdisciplinary treatment team. Treatment with a curative intent must be differentiated from a palliative one. In addition to prior treatment, resectability, age and performance status, patient wishes must be taken into consideration in treatment planning, especially considering that most therapies offer little to no overall survival benefit. Salvage surgery, chemo- and target therapies, and reirradiation are head and neck surgeon's and radiooncologist's weapons in the fight against these strong opponents. This review focuses on publications and meeting news from last year and reviews the current status of the clinical application of each treatment modality in recurrent or metastatic head and neck cancer.

Torticollis in Mice Intravenously Infected with Mycobacterium tuberculosis

PubMed Central

Magden, Elizabeth R; Weiner, Cristina M; Gilliland, Janet C; DeGroote, Mary Ann; Lenaerts, Anne J; Kendall, Lon V

2011-01-01

Female BALB/cAnNCrl (n = 170; age, 6 to 9 wk) mice were infected by intravenous inoculation of 5 × 106 cfu Mycobacterium tuberculosis strain Erdman (ATCC 35801). Between day 52 and 5 mo after infection, 10 of the 170 mice infected according to this protocol developed torticollis, including mice in treatment groups that received combination antibiotic therapy of rifampin–pyrazinamide or moxifloxacin–rifampin–pyrazinamide. Torticollis did not develop in mice receiving isoniazid–rifampin–pyrazinamide therapy, nor was it present in the cohort of aerogenically infected mice. Affected mice were euthanized, and complete necropsy evaluation was performed on 4 mice. Gross necropsy evaluation revealed typical tuberculosis lesions in lungs of infected mice. Histologic evaluation of tissues revealed granulomatous otitis media with intralesional acid-fast bacilli consistent with Mycobacterium tuberculosis. These cases represent an unusual finding specific to the intravenous mouse model of Mycobacterium tuberculosis and may represent a model of a similar condition in humans that is known as tuberculous otitis media. PMID:21439219

Torticollis in mice intravenously infected with Mycobacterium tuberculosis.

PubMed

Magden, Elizabeth R; Weiner, Cristina M; Gilliland, Janet C; DeGroote, Mary Ann; Lenaerts, Anne J; Kendall, Lon V

2011-03-01

Female BALB/cAnNCrl (n = 170; age, 6 to 9 wk) mice were infected by intravenous inoculation of 5 × 10(6) cfu Mycobacterium tuberculosis strain Erdman (ATCC 35801). Between day 52 and 5 mo after infection, 10 of the 170 mice infected according to this protocol developed torticollis, including mice in treatment groups that received combination antibiotic therapy of rifampin-pyrazinamide or moxifloxacin-rifampin-pyrazinamide. Torticollis did not develop in mice receiving isoniazid- rifampin-pyrazinamide therapy, nor was it present in the cohort of aerogenically infected mice. Affected mice were euthanized, and complete necropsy evaluation was performed on 4 mice. Gross necropsy evaluation revealed typical tuberculosis lesions in lungs of infected mice. Histologic evaluation of tissues revealed granulomatous otitis media with intralesional acid-fast bacilli consistent with Mycobacterium tuberculosis. These cases represent an unusual finding specific to the intravenous mouse model of Mycobacterium tuberculosis and may represent a model of a similar condition in humans that is known as tuberculous otitis media.

Ventricular tachycardia in post-myocardial infarction patients. Results of surgical therapy.

PubMed

Viganò, M; Martinelli, L; Salerno, J A; Minzioni, G; Chimienti, M; Graffigna, A; Goggi, C; Klersy, C; Montemartini, C

1986-05-01

This report addresses the problems related to surgical treatment of post-infarction ventricular tachycardia (VT) and is based on a 5 year experience of 36 consecutive patients. In every case the arrhythmia was unresponsive to pharmacological therapy. All patients were operated on after the completion of a diagnostic protocol including preoperative endocardial, intra-operative epi-endocardial mapping, the latter performed automatically when possible. Surgical techniques were: classical Guiraudon's encircling endocardial ventriculotomy (EEV); partial EEV, endocardial resection (ER); cryoablation or a combination of these procedures. The in-hospital mortality (30 days) was 8.3% (3 patients). During the follow-up period (1-68 months), 3 patients (9%) died of cardiac but not VT related causes. Of the survivors, 92% are VT-free. We consider electrophysiologically guided surgery a safe and reliable method for the treatment of post-infarction VT and suggest its more extensive use. We stress the importance of automatic mapping in pleomorphic and non-sustained VT, and the necessity of tailoring the surgical technique to the characteristics of each case.

Music therapy with disorders of consciousness: current evidence and emergent evidence-based practice.

PubMed

Magee, Wendy L; O'Kelly, Julian

2015-03-01

Patients with prolonged disorders of consciousness (PDOC) stemming from acquired brain injury present one of the most challenging clinical populations in neurological rehabilitation. Because of the complex clinical presentation of PDOC patients, treatment teams are confronted with many medicolegal, ethical, philosophical, moral, and religious issues in day-to-day care. Accurate diagnosis is of central concern, relying on creative approaches from skilled clinical professionals using combined behavioral and neurophysiological measures. This paper presents the latest evidence for using music as a diagnostic tool with PDOC, including recent developments in music therapy interventions and measurement. We outline standardized clinical protocols and behavioral measures to produce diagnostic outcomes and examine recent research illustrating a range of benefits of music-based methods at behavioral, cardiorespiratory, and cortical levels using video, electrocardiography, and electroencephalography methods. These latest developments are discussed in the context of evidence-based practice in rehabilitation with clinical populations. © 2014 New York Academy of Sciences.

Primary frontal sinus squamous cell carcinoma in three dogs treated with piroxicam combined with carboplatin or toceranib.

PubMed

de Vos, J; Ramos Vega, S; Noorman, E; de Vos, P

2012-09-01

In human medicine, primary frontal sinus squamous cell carcinoma (pFS-SCC) is not frequently reported. In veterinary medicine, frontal sinus SCC is exclusively described as an extension of nasal cavity SCC. To our knowledge, this is the first publication concerning canine pFS-SCC, diagnosed using histology or cytology and medical imaging, in three dogs. The tumours extended into the orbit or brain cavity, without nasal involvement. Treatment was initiated with piroxicam-carboplatin. Prolongation of carboplatin delivery with a low dose intensity was performed on dogs with a favourable initial response. Dog 1 achieved a complete remission (CR), but was euthanized 344 days after start of therapy. Dog 2, still alive 3 years after start of therapy and in CR, received 14 carboplatin deliveries. In dog 3, after changing the treatment protocol into piroxicam-toceranib, a significant tumour reduction occurred, but the dog was euthanized after 195 days because of a relapse. © 2011 Blackwell Publishing Ltd.

Smoking cessation treatment by Dutch respiratory nurses: reported practice, attitudes and perceived effectiveness.

PubMed

Kotz, D; van Litsenburg, W; van Duurling, R; van Schayck, C P; Wesseling, G J

2008-01-01

To describe Dutch respiratory nurses' current smoking cessation practices, attitudes and beliefs, and to compare these with a survey from the year 2000, before the national introduction of a protocol for the treatment of nicotine and tobacco addiction (the L-MIS protocol). Questionnaire survey among all 413 registered respiratory nurses in the Netherlands in 2006. The response rate was 62%. Seventy-seven percent of the respondents reported to have "fairly good" or "good" knowledge of all steps of the L-MIS protocol. Seven out of 10 behavioural techniques for smoking cessation from the protocol were used by more than 94% of the respondents. Seventy-four percent of the respiratory nurses recommended the use of either nicotine replacement therapy (70%) or bupropion (44%). Almost two-thirds (65% of 254) perceived lack of patient's motivation as the most important barrier for smoking cessation treatment; a four-fold increase compared to the year 2000. We conclude that respiratory nurses are compliant with the L-MIS protocol. They offer intensive support and use behavioural techniques for smoking cessation more frequently than evidence-based pharmacological aids for smoking cessation. Perceived lack of patient's motivation forms the most important threat to respiratory nurses' future smoking cessation activities. International guidelines acknowledge that respiratory patients have a more urgent need to stop smoking but have more difficulty doing so. They should be offered the most intensive smoking cessation counselling in combination with pharmacotherapy. This kind of counselling may be more feasible for respiratory nurses than for physicians who often lack time. Their efforts could be increased by reimbursing pharmacological aids for smoking cessation and by developing simple tools to systematically assess motivation to quit and psychiatric co-morbidity in smoking patients.

MatMRI and MatHIFU: software toolboxes for real-time monitoring and control of MR-guided HIFU

PubMed Central

2013-01-01

Background The availability of open and versatile software tools is a key feature to facilitate pre-clinical research for magnetic resonance imaging (MRI) and magnetic resonance-guided high-intensity focused ultrasound (MR-HIFU) and expedite clinical translation of diagnostic and therapeutic medical applications. In the present study, two customizable software tools that were developed at the Thunder Bay Regional Research Institute are presented for use with both MRI and MR-HIFU. Both tools operate in a MATLAB®; environment. The first tool is named MatMRI and enables real-time, dynamic acquisition of MR images with a Philips MRI scanner. The second tool is named MatHIFU and enables the execution and dynamic modification of user-defined treatment protocols with the Philips Sonalleve MR-HIFU therapy system to perform ultrasound exposures in MR-HIFU therapy applications. Methods MatMRI requires four basic steps: initiate communication, subscribe to MRI data, query for new images, and unsubscribe. MatMRI can also pause/resume the imaging and perform real-time updates of the location and orientation of images. MatHIFU requires four basic steps: initiate communication, prepare treatment protocol, and execute treatment protocol. MatHIFU can monitor the state of execution and, if required, modify the protocol in real time. Results Four applications were developed to showcase the capabilities of MatMRI and MatHIFU to perform pre-clinical research. Firstly, MatMRI was integrated with an existing small animal MR-HIFU system (FUS Instruments, Toronto, Ontario, Canada) to provide real-time temperature measurements. Secondly, MatMRI was used to perform T2-based MR thermometry in the bone marrow. Thirdly, MatHIFU was used to automate acoustic hydrophone measurements on a per-element basis of the 256-element transducer of the Sonalleve system. Finally, MatMRI and MatHIFU were combined to produce and image a heating pattern that recreates the word ‘HIFU’ in a tissue-mimicking heating phantom. Conclusions MatMRI and MatHIFU leverage existing MRI and MR-HIFU clinical platforms to facilitate pre-clinical research. MatMRI substantially simplifies the real-time acquisition and processing of MR data. MatHIFU facilitates the testing and characterization of new therapy applications using the Philips Sonalleve clinical MR-HIFU system. Under coordination with Philips Healthcare, both MatMRI and MatHIFU are intended to be freely available as open-source software packages to other research groups. PMID:25512856

Long-term effect of extracorporeal shock wave therapy on the treatment of chronic pelvic pain syndrome due to non bacterial prostatitis.

PubMed

Moayednia, Amir; Haghdani, Saeid; Khosrawi, Saeid; Yousefi, Elham; Vahdatpour, Babak

2014-04-01

There is limited evidence about the chronic pelvic pain syndrome (CPPS) treatment by shockwave therapy, and the aim of this study was to evaluate the effect of extracorporeal shockwave therapy on CPPS due to non bacterial prostatitis in a long-term period. In a follow-up survey, 40 patients with CPPS (that were randomly distributed into the treatment or sham groups were evaluated at 16, 20, and 24 weeks. In the treatment group, patients were treated by extracorporeal shock wave therapy (ESWT) once a week for 4 weeks by a protocol of 3000 impulses, 0.25 mJ/m(2) and 3 Hz of frequency. 0.05 mJ/m(2) were added in each week. In the sham group, the same protocol was applied, but with the probe being turned off. The follow-up assessments were done by visual analog scale for pain and National Institutes of Health-developed Chronic Prostatitis Symptom Index (NIH-CPSI). Data were compared using independent t-test or analysis of variences. Three patients did not complete the study protocol, 37 patients were evlauated (19 patients in treatment and 18 patients in the sham group). At week 24, the mean of pain score, urinary score, quality-of-life and NIH-CPSI score between two groups were not statistically different. Although, ESWT therapy as a safe and effective therapy in CPPS in short-term follow-up has been established, its long-term efficacy was not supported by this study.

Penile rehabilitation protocol after robot-assisted radical prostatectomy: assessment of compliance with phosphodiesterase type 5 inhibitor therapy and effect on early potency.

PubMed

Lee, Daniel J; Cheetham, Philippa; Badani, Ketan K

2010-02-01

Therapy (case series). 4. To evaluate factors that affect compliance in men who enroll in a phosphodiesterase type 5 inhibitor (PDE5I) protocol after nerve-sparing robot-assisted prostatectomy (RAP), and report on short-term outcomes, as PDE5Is may help restore erectile function after RAP and patient adherence to the regimen is a factor that potentially can affect outcome. We prospectively followed 77 men who had nerve-sparing RAP and enrolled in a postoperative penile rehabilitation protocol. The men received either sildenafil citrate or tadalafil three times weekly. The minimum follow-up was 8 weeks. Potency was defined as erection adequate for penetration and complete intercourse. Compliance was defined as men adhering to the regimen for > or =2 months. The mean age of the cohort was 57.8 years and the median follow-up was 8 months. In all, 32% of the men discontinued the therapy <2 months after RAP and were deemed noncompliant with an additional 39% discontinuing therapy by 6 months, with the high cost of medication being the primary reason (65%). Long-term compliance and preoperative erectile dysfunction were independent predictors of potency return after adjusting for age and nerve sparing. The high cost of medication remains a significant barrier to maintaining therapy. Noncompliance to PDE5I therapy in a tertiary care centre was much higher than reported in clinical trial settings. With longer-term follow-up, we need to further define the factors that improve overall recovery of sexual function after RAP.

Key process indicators of mortality in the implementation of protocol-driven therapy for severe sepsis.

PubMed

Wang, Jiun-Long; Chin, Chun-Shih; Chang, Ming-Chen; Yi, Chi-Yuan; Shih, Sou-Jen; Hsu, Jeng-Yuan; Wu, Chieh-Liang

2009-10-01

Severe sepsis and septic shock are life-threatening disorders. Integrating treatments into a bundle strategy has been proposed to facilitate timely resuscitation, but is difficult to implement. We implemented protocol-driven therapy for severe sepsis, and analyzed retrospectively the key process indicators of mortality in managing sepsis. Continuous quality improvement was begun to implement a tailored protocol-driven therapy for sepsis in a 24-bed respiratory intensive care unit (RICU) of Taichung Veterans General Hospital from January 2007 to February 2008. Patients, who were admitted to the RICU directly, or within 24 hours, were enrolled if they met the criteria for severe sepsis and septic shock. Disease severity [Acute Physiology and Chronic Health Evaluation (APACHE) II and lactate level], causes of sepsis, comorbidity and site of sepsis onset were recorded. Process-of-care indicators included resuscitation time (Tr-s), RICU bed availability (Ti-s) and the ratio of completing the elements of the protocol at 1, 2, 4 and 6 hours. The structure and process-of-care indicators reflated to mortality at 7 days after RICU admission and at RICU discharge were identified retrospectively. Eighty-six patients (mean age, 71 +/- 14 years, 72 men, 14 women, APACHE II, 25.0 +/- 7.0) were enrolled. APACHE II scores and lactate levels were higher for mortality than survival at 7 days after RICU admission (p < 0.01). For the process-of-care indicators, Ti-s (562.2 +/- 483.3 vs.1017.3 +/- 557.8 minutes, p = 0.03) and Tr-s (60.7 +/- 207.8 vs. 248.5 +/- 453.1 minutes, p = 0.07) were shorter for survival than mortality at 7 days after RICU admission. The logistic regression study showed that Tr-s was an important indicator. The ratio of completing the elements of protocols at 1, 2, 4 and 6 hours ranged from 70% to 90% and was not related to mortality. Protocol-driven therapy for sepsis was put into clinical practice. Early resuscitation and ICU bed availability were key process indicators in managing sepsis, to reduce mortality.

Humanistic therapies versus other psychological therapies for depression

PubMed Central

Churchill, Rachel; Davies, Philippa; Caldwell, Deborah; Moore, Theresa HM; Jones, Hannah; Lewis, Glyn; Hunot, Vivien

2014-01-01

This is the protocol for a review and there is no abstract. The objectives are as follows: To examine the effectiveness and acceptability of all humanistic therapies compared with all other psychological therapy approaches for acute depression.To examine the effectiveness and acceptability of different humanistic therapy models (person-centred, gestalt, process-experiential, transactional analysis, existential and non-directive therapies) compared with all other psychological therapy approaches for acute depression.To examine the effectiveness and acceptability of all humanistic therapies compared with different psychological therapy approaches (psychodynamic, behavioural, humanistic, integrative, cognitive-behavioural) for acute depression. PMID:25278809

Combining bio-electrospraying with gene therapy: a novel biotechnique for the delivery of genetic material via living cells.

PubMed

Ward, Eliot; Chan, Emma; Gustafsson, Kenth; Jayasinghe, Suwan N

2010-05-01

The investigations reported in this article demonstrate the ability of bio-electrosprays and cell electrospinning to deliver a genetic construct in association with living cells. Previous studies on both bio-electrosprays and cell electrospinning demonstrated great promise for tissue engineering and regenerative biology/medicine. The investigations described herein widen the applicability of these biotechniques by combining gene therapy protocols, resulting in a novel drug delivery methodology previously unexplored. In these studies a human cell line was transduced with recombinant self-inactivating lentiviral particles. These particles incorporated a green fluorescent protein fused to an endosomal targeting construct. This construct encodes a peptide, which can subsequently be detected on the surface of cells by specific T-cells. The transduced cell line was subsequently manipulated in association with either bio-electrospraying or cell electrospinning. Hence this demonstrates (i) the ability to safely handle genetically modified living cells and (ii) the ability to directly form pre-determined architectures bearing living therapeutic cells. This merged technology demonstrates a unique approach for directly forming living therapeutic architectures for controlled and targeted release of experimental cells/genes, as well as medical cell/gene therapeutics for a plethora of biological and medical applications. Hence, such developments could be applied to personalised medicine.

Body System Effects of a Multi-Modal Training Program Targeting Chronic, Motor Complete Thoracic Spinal Cord Injury.

PubMed

Gant, Katie L; Nagle, Kathleen G; Cowan, Rachel E; Field-Fote, Edelle C; Nash, Mark S; Kressler, Jochen; Thomas, Christine K; Castellanos, Mabelin; Widerström-Noga, Eva; Anderson, Kimberly D

2018-02-01

The safety and efficacy of pharmacological and cellular transplantation strategies are currently being evaluated in people with spinal cord injury (SCI). In studies of people with chronic SCIs, it is thought that functional recovery will be best achieved when drug or cell therapies are combined with rehabilitation protocols. However, any functional recovery attributed to the therapy may be confounded by the conditioned state of the body and by training-induced effects on neuroplasticity. For this reason, we sought to investigate the effects of a multi-modal training program on several body systems. The training program included body-weight-supported treadmill training for locomotion, circuit resistance training for upper body conditioning, functional electrical stimulation for activation of sublesional muscles, and wheelchair skills training for overall mobility. Eight participants with chronic, thoracic-level, motor-complete SCI completed the 12-week training program. After 12 weeks, upper extremity muscular strength improved significantly for all participants, and some participants experienced improvements in function, which may be explained by increased strength. Neurological function did not change. Changes in pain and spasticity were highly variable between participants. This is the first demonstration of the effect of this combination of four training modalities. However, balancing participant and study-site burden with capturing meaningful outcome measures is also an important consideration.

Efficacy of a cognitive-behavioral treatment for insomnia and nightmares in Afghanistan and Iraq veterans with PTSD.

PubMed

Margolies, Skye Ochsner; Rybarczyk, Bruce; Vrana, Scott R; Leszczyszyn, David J; Lynch, John

2013-10-01

Sleep disturbances are a core and salient feature of posttraumatic stress disorder (PTSD). Pilot studies have indicated that combined cognitive-behavioral therapy for insomnia (CBT-I) and imagery rehearsal therapy (IRT) for nightmares improves sleep as well as PTSD symptoms. The present study randomized 40 combat veterans (mean age 37.7 years; 90% male and 60% African American) who served in Afghanistan and/or Iraq (Operation Enduring Freedom [OEF]/Operation Iraqi Freedom [OIF]) to 4 sessions of CBT-I with adjunctive IRT or a waitlist control group. Two thirds of participants had nightmares at least once per week and received the optional IRT module. At posttreatment, veterans who participated in CBT-I/IRT reported improved subjectively and objectively measured sleep, a reduction in PTSD symptom severity and PTSD-related nighttime symptoms, and a reduction in depression and distressed mood compared to the waitlist control group. The findings from this first controlled study with OEF/OIF veterans suggest that CBT-I combined with adjunctive IRT may hold promise for reducing both insomnia and PTSD symptoms. Given the fact that only half of the patients with nightmares fully implemented the brief IRT protocol, future studies should determine if this supplement adds differential efficacy to CBT-I alone. © 2013 Wiley Periodicals, Inc.

Non-Invasive Transcranial Brain Therapy Guided by CT Scans: an In Vivo Monkey Study

NASA Astrophysics Data System (ADS)

Marquet, F.; Pernot, M.; Aubry, J.-F.; Montaldo, G.; Tanter, M.; Boch, A.-L.; Kujas, M.; Seilhean, D.; Fink, M.

2007-05-01

Brain therapy using focused ultrasound remains very limited due to the strong aberrations induced by the skull. A minimally invasive technique using time-reversal was validated recently in-vivo on 20 sheeps. But such a technique requires a hydrophone at the focal point for the first step of the time-reversal procedure. A completely noninvasive therapy requires a reliable model of the acoustic properties of the skull in order to simulate this first step. 3-D simulations based on high-resolution CT images of a skull have been successfully performed with a finite differences code developed in our Laboratory. Thanks to the skull porosity, directly extracted from the CT images, we reconstructed acoustic speed, density and absorption maps and performed the computation. Computed wavefronts are in good agreement with experimental wavefronts acquired through the same part of the skull and this technique was validated in-vitro in the laboratory. A stereotactic frame has been designed and built in order to perform non invasive transcranial focusing in vivo. Here we describe all the steps of our new protocol, from the CT-scans to the therapy treatment and the first in vivo results on a monkey will be presented. This protocol is based on protocols already existing in radiotherapy.

A Mirror Therapy-Based Action Observation Protocol to Improve Motor Learning After Stroke.

PubMed

Harmsen, Wouter J; Bussmann, Johannes B J; Selles, Ruud W; Hurkmans, Henri L P; Ribbers, Gerard M

2015-07-01

Mirror therapy is a priming technique to improve motor function of the affected arm after stroke. To investigate whether a mirror therapy-based action observation (AO) protocol contributes to motor learning of the affected arm after stroke. A total of 37 participants in the chronic stage after stroke were randomly allocated to the AO or control observation (CO) group. Participants were instructed to perform an upper-arm reaching task as fast and as fluently as possible. All participants trained the upper-arm reaching task with their affected arm alternated with either AO or CO. Participants in the AO group observed mirrored video tapes of reaching movements performed by their unaffected arm, whereas participants in the CO group observed static photographs of landscapes. The experimental condition effect was investigated by evaluating the primary outcome measure: movement time (in seconds) of the reaching movement, measured by accelerometry. Movement time decreased significantly in both groups: 18.3% in the AO and 9.1% in the CO group. Decrease in movement time was significantly more in the AO compared with the CO group (mean difference = 0.14 s; 95% confidence interval = 0.02, 0.26; P = .026). The present study showed that a mirror therapy-based AO protocol contributes to motor learning after stroke. © The Author(s) 2014.

[Posterior vitrectomy with gas endotamponade and retinal laser therapy in treatment of patients with macular complications of the optic disc pit].

PubMed

Cywiński, Adam; Kałużny, Jakub; Ferda, Daniela; Piwońska-Lobermajer, Anna

2015-01-01

Retrospective evaluation of functional and anatomical treatment outcomes in patients with macular cornplications of optic disc pit. 9 patients (eyes) underwent central posterior vitrectomy in conjunction with posterior vitreous detachment, retinal laser therapy to the optic disc pit area and endotamponade with expansile gas. It was followed by the patient's forced positioning (recommended for a few days especially at night), which ended the treatment protocol. Improved anatomical relationships, accompanied by functional improvement were achieved in each reported case. The resolution of macular lesions was slow, lasting even for several months. Too long delay in performing the surgery (over 5 months since the onset of visual impairment) was associated with the development of retinal complications, mainly macular hole formation, most likely caused by the long-term ischemia. The central posterior vitrectomy combined with posterior vitreous detachment, laser therapy, andd expansile gas tamponade offers good outcomes in patients with retinal complications of optic disc pit. Surgery performed shortly after the onset of visual dysfunction gives the best functional outcomes. Restoration of normal anatomical relationships is a long-term process. In some cases, though, these abnormalities may not resolve completely.

Optimizing Culture Medium Composition to Improve Oligodendrocyte Progenitor Cell Yields In Vitro from Subventricular Zone-Derived Neural Progenitor Cell Neurospheres

PubMed Central

Franco, Paula G.; Pasquini, Juana M.; Silvestroff, Lucas

2015-01-01

Neural Stem and Progenitor Cells (NSC/NPC) are gathering tangible recognition for their uses in cell therapy and cell replacement therapies for human disease, as well as a model system to continue research on overall neural developmental processes in vitro. The Subventricular Zone is one of the largest NSC/NPC niches in the developing mammalian Central Nervous System, and persists through to adulthood. Oligodendrocyte progenitor cell (OPC) enriched cultures are usefull tools for in vitro studies as well as for cell replacement therapies for treating demyelination diseases. We used Subventricular Zone-derived NSC/NPC primary cultures from newborn mice and compared the effects of different growth factor combinations on cell proliferation and OPC yield. The Platelet Derived Growth Factor-AA and BB homodimers had a positive and significant impact on OPC generation. Furthermore, heparin addition to the culture media contributed to further increase overall culture yields. The OPC generated by this protocol were able to mature into Myelin Basic Protein-expressing cells and to interact with neurons in an in vitro co-culture system. As a whole, we describe an optimized in vitro method for increasing OPC. PMID:25837625

Innovative Approaches for Immune Tolerance to Factor VIII in the Treatment of Hemophilia A

PubMed Central

Sherman, Alexandra; Biswas, Moanaro; Herzog, Roland W.

2017-01-01

Hemophilia A (coagulation factor VIII deficiency) is a debilitating genetic disorder that is primarily treated with intravenous replacement therapy. Despite a variety of factor VIII protein formulations available, the risk of developing anti-dug antibodies (“inhibitors”) remains. Overall, 20–30% of patients with severe disease develop inhibitors. Current clinical immune tolerance induction protocols to eliminate inhibitors are not effective in all patients, and there are no prophylactic protocols to prevent the immune response. New experimental therapies, such as gene and cell therapies, show promising results in pre-clinical studies in animal models of hemophilia. Examples include hepatic gene transfer with viral vectors, genetically engineered regulatory T cells (Treg), in vivo Treg induction using immune modulatory drugs, and maternal antigen transfer. Furthermore, an oral tolerance protocol is being developed based on transgenic lettuce plants, which suppressed inhibitor formation in hemophilic mice and dogs. Hopefully, some of these innovative approaches will reduce the risk of and/or more effectively eliminate inhibitor formation in future treatment of hemophilia A. PMID:29225598

Effect of a preoperative protocol of aerobic physical therapy on the quality of life of patients with adolescent idiopathic scoliosis: a randomized clinical study.

PubMed

dos Santos Alves, Vera Lucia; Alves da Silva, Renato Jose Azevedo Leite; Avanzi, Osmar

2014-06-01

Patients with adolescent idiopathic scoliosis (AIS) have lower potential for physical activity because of lung dysfunction and lower muscle strength, which can be reversed by the cardiorespiratory and musculoskeletal conditioning provided by standardized physical activities. We conducted a study to determine if a preoperative protocol of aerobic exercise would improve quality of life (QoL) both before and after training and if there would be any differences between patients who received the therapy and those who did not. Patients with the indication of surgical correction of AIS were randomized to receive or not receive a 4-month preoperative course of aerobic physical training. At baseline and after 4 months, they were evaluated with the Short Form-36 questionnaire (SF-36). QoL scores improved for the study group but did not change for the control group. In all QoL domains, the study group's mean score increased significantly between baseline and 4 months. We concluded that the proposed preoperative physical therapy protocol improved the QoL of patients with AIS.

ESCAschool study: trial protocol of an adaptive treatment approach for school-age children with ADHD including two randomised trials.

PubMed

Döpfner, Manfred; Hautmann, Christopher; Dose, Christina; Banaschewski, Tobias; Becker, Katja; Brandeis, Daniel; Holtmann, Martin; Jans, Thomas; Jenkner, Carolin; Millenet, Sabina; Renner, Tobias; Romanos, Marcel; von Wirth, Elena

2017-07-24

The ESCAschool study addresses the treatment of school-age children with attention-deficit/hyperactivity disorder (ADHD) in a large multicentre trial. It aims to investigate three interrelated topics: (i) Clinical guidelines often recommend a stepped care approach, including different treatment strategies for children with mild to moderate and severe ADHD symptoms, respectively. However, this approach has not yet been empirically validated. (ii) Behavioural interventions and neurofeedback have been shown to be effective, but the superiority of combined treatment approaches such as medication plus behaviour therapy or medication plus neurofeedback compared to medication alone remains questionable. (iii) Growing evidence indicates that telephone-assisted self-help interventions are effective in the treatment of ADHD. However, larger randomised controlled trials (RCTs) are lacking. This report presents the ESCAschool trial protocol. In an adaptive treatment design, two RCTs and additional observational treatment arms are considered. The target sample size of ESCAschool is 521 children with ADHD. Based on their baseline ADHD symptom severity, the children will be assigned to one of two groups (mild to moderate symptom group and severe symptom group). The adaptive design includes two treatment phases (Step 1 and Step 2). According to clinical guidelines, different treatment protocols will be followed for the two severity groups. In the moderate group, the efficacy of telephone-assisted self-help for parents and teachers will be tested against waitlist control in Step 1 (RCT I). The severe group will receive pharmacotherapy combined with psychoeducation in Step 1. For both groups, treatment response will be determined after Step 1 treatment (no, partial or full response). In severe group children demonstrating partial response to medication, in Step 2, the efficacy of (1) counselling, (2) behaviour therapy and (3) neurofeedback will be tested (RCT II). All other treatment arms in Step 2 (severe group: no or full response; moderate group: no, partial or full response) are observational. The ESCAschool trial will provide evidence-based answers to several important questions for clinical practice following a stepped care approach. The adaptive study design will also provide new insights into the effects of additional treatments in children with partial response. German Clinical Trials Register (DRKS) DRKS00008973 . Registered 18 December 2015.

Efficacy of Low-Intensity Extracorporeal Shock Wave Therapy on Men With Chronic Pelvic Pain Syndrome Refractory to 3-As Therapy.

PubMed

Guu, Shiao-Jin; Geng, Jiun-Hung; Chao, I-Ting; Lin, Hui-Tzu; Lee, Yung-Chin; Juan, Yung-Shun; Liu, Chia-Chu; Wang, Chii-Jye; Tsai, Chia-Chun

2018-03-01

Managing patients with chronic pelvic pain syndrome (CPPS) refractory to the traditional 3-As therapy (antibiotics, alpha-blockers, and anti-inflammatories) is a challenging task. Low-intensity extracorporeal shock wave therapy (LI-ESWT) was recently reported to be able to improve pain, urinary symptoms, and even sexual function by inducing neovascularization and anti-inflammation, reducing muscle tone, and influencing nerve impulses. This study evaluates whether combined treatment with LI-ESWT can restore clinical ability and quality of life (QoL) in patients refractory to 3-As therapy. This was an open-label, single-arm prospective study. Patients with CPPS without more than a 6-point decrease in the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) total score under the maximal dosage of 3-As therapy were enrolled. LI-ESWT treatment consisted of 3,000 shock waves administered once weekly for 4 weeks. The NIH-CPSI, visual analog scale (VAS) score, International Prostate Symptom Score (IPSS), and the five-item version of the International Index of Erectile Function (IIEF-5) were used to evaluate efficacy at 1, 4, and 12 weeks after LI-ESWT. Thirty-three patients were enrolled in this study. After LI-ESWT treatment, 27 of the 33 patients (81.82%) had a successful response to LI-ESWT, with a decrease of 3.29 and 5.97 in the VAS score and total IPSS at the 3-month follow-up. Waist circumference was the only significant predictor of a successful response to LI-ESWT. LI-ESWT can serve as a salvage therapy for patients with CPPS refractory to traditional 3-As therapy. Further studies are needed to determine an adequate therapeutic protocol and important predictors in patients with different CPPS etiologies.

Protocol vulnerability detection based on network traffic analysis and binary reverse engineering.

PubMed

Wen, Shameng; Meng, Qingkun; Feng, Chao; Tang, Chaojing

2017-01-01

Network protocol vulnerability detection plays an important role in many domains, including protocol security analysis, application security, and network intrusion detection. In this study, by analyzing the general fuzzing method of network protocols, we propose a novel approach that combines network traffic analysis with the binary reverse engineering method. For network traffic analysis, the block-based protocol description language is introduced to construct test scripts, while the binary reverse engineering method employs the genetic algorithm with a fitness function designed to focus on code coverage. This combination leads to a substantial improvement in fuzz testing for network protocols. We build a prototype system and use it to test several real-world network protocol implementations. The experimental results show that the proposed approach detects vulnerabilities more efficiently and effectively than general fuzzing methods such as SPIKE.

Combining Mindfulness Meditation with Cognitive-Behavior Therapy for Insomnia

PubMed Central

Ong, Jason C.; Shapiro, Shauna L.; Manber, Rachel

2009-01-01

This treatment-development study is a Stage I evaluation of an intervention that combines mindfulness meditation with cognitive-behavior therapy for insomnia (CBT-I). Thirty adults who met research diagnostic criteria for Psychophysiological Insomnia (Edinger et al., 2004) participated in a 6-week, multi-component group intervention using mindfulness meditation, sleep restriction, stimulus control, sleep education, and sleep hygiene. Sleep diaries and self-reported pre-sleep arousal were assessed weekly while secondary measures of insomnia severity, arousal, mindfulness skills, and daytime functioning were assessed at pre-treatment and post-treatment. Data collected on recruitment, retention, compliance, and satisfaction indicate that the treatment protocol is feasible to deliver and is acceptable for individuals seeking treatment for insomnia. The overall patterns of change with treatment demonstrated statistically and clinically significant improvements in several nighttime symptoms of insomnia as well as statistically significant reductions in pre-sleep arousal, sleep effort, and dysfunctional sleep-related cognitions. In addition, a significant correlation was found between the number of meditation sessions and changes on a trait measure of arousal. Together, the findings indicate that mindfulness meditation can be combined with CBT-I and this integrated intervention is associated with reductions in both sleep and sleep-related arousal. Further testing of this intervention using randomized controlled trials is warranted to evaluate the efficacy of the intervention for this population and the specific effects of each component on sleep and both psychological and physiological arousal. PMID:18502250

Combined motor cortex and spinal cord neuromodulation promotes corticospinal system functional and structural plasticity and motor function after injury.

PubMed

Song, Weiguo; Amer, Alzahraa; Ryan, Daniel; Martin, John H

2016-03-01

An important strategy for promoting voluntary movements after motor system injury is to harness activity-dependent corticospinal tract (CST) plasticity. We combine forelimb motor cortex (M1) activation with co-activation of its cervical spinal targets in rats to promote CST sprouting and skilled limb movement after pyramidal tract lesion (PTX). We used a two-step experimental design in which we first established the optimal combined stimulation protocol in intact rats and then used the optimal protocol in injured animals to promote CST repair and motor recovery. M1 was activated epidurally using an electrical analog of intermittent theta burst stimulation (iTBS). The cervical spinal cord was co-activated by trans-spinal direct current stimulation (tsDCS) that was targeted to the cervical enlargement, simulated from finite element method. In intact rats, forelimb motor evoked potentials (MEPs) were strongly facilitated during iTBS and for 10 min after cessation of stimulation. Cathodal, not anodal, tsDCS alone facilitated MEPs and also produced a facilitatory aftereffect that peaked at 10 min. Combined iTBS and cathodal tsDCS (c-tsDCS) produced further MEP enhancement during stimulation, but without further aftereffect enhancement. Correlations between forelimb M1 local field potentials and forelimb electromyogram (EMG) during locomotion increased after electrical iTBS alone and further increased with combined stimulation (iTBS+c-tsDCS). This optimized combined stimulation was then used to promote function after PTX because it enhanced functional connections between M1 and spinal circuits and greater M1 engagement in muscle contraction than either stimulation alone. Daily application of combined M1 iTBS on the intact side and c-tsDCS after PTX (10 days, 27 min/day) significantly restored skilled movements during horizontal ladder walking. Stimulation produced a 5.4-fold increase in spared ipsilateral CST terminations. Combined neuromodulation achieves optimal motor recovery and substantial CST outgrowth with only 27 min of daily stimulation compared with 6h, as in our prior study, making it a potential therapy for humans with spinal cord injury. Copyright © 2015 Elsevier Inc. All rights reserved.

Combined motor cortex and spinal cord neuromodulation promotes corticospinal system functional and structural plasticity and motor function after injury

PubMed Central

Song, Weiguo; Amer, Alzahraa; Ryan, Daniel; Martin, John H.

2016-01-01

An important strategy for promoting voluntary movements after motor system injury is to harness activity-dependent corticospinal tract (CST) plasticity. We combine forelimb motor cortex (M1) activation with co-activation of its cervical spinal targets in rats to promote CST sprouting and skilled limb movement after pyramidal tract lesion (PTX). We used a two-step experimental design in which we first established the optimal combined stimulation protocol in intact rats and then used the optimal protocol in injured animals to promote CST repair and motor recovery. M1 was activated epidurally using an electrical analog of intermittent theta burst stimulation (iTBS). The cervical spinal cord was co-activated by trans-spinal direct current stimulation (tsDCS) that was targeted to the cervical enlargement, simulated from finite element method. In intact rats, forelimb motor evoked potentials (MEPs) were strongly facilitated during iTBS and for 10 minutes after cessation of stimulation. Cathodal, not anodal, tsDCS alone facilitated MEPs and also produced a facilitatory aftereffect that peaked at 10 minutes. Combined iTBS and cathodal tsDCS (c-tsDCS) produced further MEP enhancement during stimulation, but without further aftereffect enhancement. Correlations between forelimb M1 local field potentials and forelimb electromyogram (EMG) during locomotion increased after electrical iTBS alone and further increased with combined stimulation (iTBS + c-tsDCS). This optimized combined stimulation was then used to promote function after PTX because it enhanced functional connections between M1 and spinal circuits and greater M1 engagement in muscle contraction than either stimulation alone. Daily application of combined M1 iTBS on the intact side and c-tsDCS after PTX (10 days, 27 minutes/day) significantly restored skilled movements during horizontal ladder walking. Stimulation produced a 5.4-fold increase in spared ipsilateral CST terminations. Combined neuromodulation achieves optimal motor recovery and substantial CST outgrowth with only 27 minutes of daily stimulation compared with 6 hours, as in our prior study, making it a potential therapy for humans with spinal cord injury. PMID:26708732

Chapter 23: Combined Heat and Power Evaluation Protocol. The Uniform Methods Project: Methods for Determining Energy Efficiency Savings for Specific Measures

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

Kurnik, Charles W.; Simons, George; Barsun, Stephan

The main focus of most evaluations is to determine the energy-savings impacts of the installed measure. This protocol defines a combined heat and power (CHP) measure as a system that sequentially generates both electrical energy and useful thermal energy from one fuel source at a host customer's facility or residence. This protocol is aimed primarily at regulators and administrators of ratepayer-funded CHP programs; however, project developers may find the protocol useful to understand how CHP projects are evaluated.

Impact of a Respiratory Therapy Assess-and-Treat Protocol on Adult Cardiothoracic ICU Readmissions.

PubMed

Dailey, Robert T; Malinowski, Thomas; Baugher, Mitchel; Rowley, Daniel D

2017-05-01

The purpose of this retrospective medical record review was to report on recidivism to the ICU among adult postoperative cardiac and thoracic patients managed with a respiratory therapy assess-and-treat (RTAT) protocol. Our primary null hypothesis was that there would be no difference in all-cause unexpected readmissions and escalations between the RTAT group and the physician-ordered respiratory care group. Our secondary null hypothesis was that there would be no difference in primary respiratory-related readmissions, ICU length of stay, or hospital length of stay. We reviewed 1,400 medical records of cardiac and thoracic postoperative subjects between January 2015 and October 2016. The RTAT is driven by a standardized patient assessment tool, which is completed by a registered respiratory therapist. The tool develops a respiratory severity score for each patient and directs interventions for bronchial hygiene, aerosol therapy, and lung inflation therapy based on an algorithm. The protocol period commenced on December 1, 2015, and continued through October 2016. Data relative to unplanned admissions to the ICU for all causes as well as respiratory-related causes were evaluated. There was a statistically significant difference in the all-cause unplanned ICU admission rate between the RTAT (5.8% [95% CI 4.3-7.9]) and the physician-ordered respiratory care (8.8% [95% CI 6.9-11.1]) groups ( P = .034). There was no statistically significant difference in respiratory-related unplanned ICU admissions with RTAT (36% [95% CI 22.7-51.6]) compared with the physician-ordered respiratory care (53% [95% CI 41.1-64.8]) group ( P = .09). The RTAT protocol group spent 1 d less in the ICU ( P < .001) and in the hospital ( P < .001). RTAT protocol implementation demonstrated a statistically significant reduction in all-cause ICU readmissions. The reduction in respiratory-related ICU readmissions did not reach statistical significance. Copyright © 2017 by Daedalus Enterprises.

An Ultralow-Dose 1-Day Protocol With Activities Lower Than 20 MBq for the Detection of Sentinel Lymph Nodes in Breast Cancer-Experiences After 150 Cases.

PubMed

Kolberg, Hans-Christian; Afsah, Shabnam; Kuehn, Thorsten; Winzer, Ute; Akpolat-Basci, Leyla; Stephanou, Miltiades; Wetzig, Sarah; Hoffmann, Oliver; Liedtke, Cornelia

2017-01-01

Common protocols for the detection of sentinel lymph nodes in early breast cancer often include the injection of the tracer 1 day before surgery. In order to detect enough activity on the day of surgery, the applied activity in many protocols is as high as several hundred MBq. So far, very few protocols with an activity below 20 MBq have been reported. We developed an ultralow-dose 1-day protocol with a mean activity lower than 20 MBq in order to reduce radiation exposure for patients and staff. Here, we are presenting our experiences in 150 consecutive cases. A total of 150 patients with clinically and sonographically negative axilla and no multicentricity underwent a sentinel lymph node biopsy using an ultralow-dose protocol performed on the day of surgery. No patient received systemic therapy prior to sentinel node biopsy. After peritumoral injection of the tracer Technetium-99m, a lymphoscintigraphy was performed in all cases. Seven minutes before the first cut, we injected 5 mL of blue dye in the region of the areola. In 148 (98.7%) of 150 patients, at least 1 sentinel lymph node could be identified by lymphoscintigraphy; the detection rate during surgery with combined tracers Technetium-99m and blue dye was 100%. The mean applied activity was 17.8 MBq (9-20). A mean number of 1.3 (0-5) sentinel lymph nodes were identified by lymphoscintigraphy and a mean number of 1.8 (1-5) sentinel lymph nodes were removed during sentinel lymph node biopsy. Ultralow-dose 1-day protocols with an activity lower than 20 MBq are a safe alternative to 1-day or 2-day protocols with significantly higher radiation doses in primary surgery for early breast cancer. Using Technetium-99m and blue dye in a dual tracer approach, detection rates of 100% are possible in clinical routine in order to reduce radiation exposure for patients and staff.

Treatment of Pediatric Obsessive Compulsive Disorder Utilizing Parent-Facilitated Acceptance and Commitment Therapy

ERIC Educational Resources Information Center

Barney, Jennifer Y.; Field, Clint E.; Morrison, Kate L.; Twohig, Michael P.

2017-01-01

Acceptance and commitment therapy (ACT) is a modern form of cognitive behavior therapy that uses acceptance and mindfulness-based procedures to address clinical issues. A brief protocol of ACT was used with 3 children ages 10 and 11 years who were diagnosed with obsessive compulsive disorder (OCD). Results showed notable and clinically significant…

Study Protocol for a randomized controlled trial of mentalization based therapy against specialist supportive clinical management in patients with both eating disorders and symptoms of borderline personality disorder

PubMed Central

2014-01-01

Background The NOURISHED study: Nice OUtcomes for Referrals with Impulsivity, Self Harm and Eating Disorders. Eating Disorders (ED) and Borderline Personality Disorder (BPD) are both difficult to treat and the combination presents particular challenges. Both are associated with vulnerability to loss of mentalization (awareness of one’s own and others’ emotional state). In BPD, Mentalization Based therapy (MBT) has been found effective in reducing symptoms. In this trial we investigate the effectiveness and cost-effectiveness of MBT adapted for Eating disorders (Mentalization Based Therapy for Eating Disorders (MBT-ED)) compared to a standard comparison treatment, Specialist Supportive Clinical Management (SSCM-ED) in patients with a combination of an Eating Disorder and either a diagnosis of BPD or a history of self-harm and impulsivity in the previous 12 months. Methods/Design We will complete a multi-site single-blind randomized controlled trial (RCT) of MBT-ED vs SSCM-ED. Participants will be recruited from three Eating Disorder Services and two Borderline Personality Disorder Services in London. Participants allocated to MBT-ED will receive one year of weekly group and individual therapy and participants allocated to SSCM-ED will receive 20 sessions of individual therapy over 1 year. In addition, participants in both groups will have access to up to 5 hours of dietetic advice. The primary outcome measure is the global score on the Eating Disorders Examination. Secondary outcome measures include total score on the Zanarini BPD scale, the Object Relations Inventory, the Depression Anxiety Stress Scales, quality of life and cost-effectiveness. Measures are taken at recruitment and at 6 month intervals up to 18 months. Discussion This is the first Randomised Controlled Trial of MBT-ED in patients with eating disorders and symptoms of BPD and will provide evidence to inform therapy decisions in this group of patients. During MBT-ED mentalization is encouraged, while in SSCM-ED it is not overtly addressed. This study will help elucidate mechanisms of change in the two therapies and analysis of therapy and interview transcripts will provide qualitative information about the conduct of therapy and changes in mentalization and object relations. Trial registration ISRCTN51304415 PMID:24555511

Gene Therapy in Fanconi Anemia: A Matter of Time, Safety and Gene Transfer Tool Efficiency.

PubMed

Verhoeyen, Els; Roman-Rodriguez, Francisco Jose; Cosset, Francois-Loic; Levy, Camille; Rio, Paula

2017-01-01

Fanconi anemia (FA) is a rare genetic syndrome characterized by progressive marrow failure. Gene therapy by infusion of FA-corrected autologous hematopoietic stem cells (HSCs) may offer a potential cure since it is a monogenetic disease with mutations in the FANC genes, coding for DNA repair enzymes [1]. However, the collection of hCD34+-cells in FA patients implies particular challenges because of the reduced numbers of progenitor cells present in their bone marrow (BM) [2] or mobilized peripheral blood [3-5]. In addition, the FA genetic defect fragilizes the HSCs [6]. These particular features might explain why the first clinical trials using murine leukemia virus derived retroviral vectors conducted for FA failed to show engraftment of corrected cells. The gene therapy field is now moving towards the use of lentiviral vectors (LVs) evidenced by recent succesful clinical trials for the treatment of patients suffering from adrenoleukodystrophy (ALD) [7], β-thalassemia [8], metachromatic leukodystrophy [9] and Wiskott-Aldrich syndrome [10]. LV trials for X-linked severe combined immunodificiency and Fanconi anemia (FA) defects were recently initiated [11, 12]. Fifteen years of preclinical studies using different FA mouse models and in vitro research allowed us to find the weak points in the in vitro culture and transduction conditions, which most probably led to the initial failure of FA HSC gene therapy. In this review, we will focus on the different obstacles, unique to FA gene therapy, and how they have been overcome through the development of optimized protocols for FA HSC culture and transduction and the engineering of new gene transfer tools for FA HSCs. These combined advances in the field hopefully will allow the correction of the FA hematological defect in the near future. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Dilemma-focused intervention for unipolar depression: a treatment manual.

PubMed

Feixas, Guillem; Compañ, Victoria

2016-07-12

This article introduces a new treatment protocol for depression. Based on previous research which indicated the presence of cognitive conflicts in depression, this study created an intervention manual to address these conflicts. The therapy manual for depressive patients followed the guideline for inclusion in clinical trials (stage II), which has received high recognition. A preliminary version (stage I) of this manual was formulated based on other, more general dilemma-focused therapy publications, inspired by personal construct theory (PCT), and input from clinical experience. The resulting version was then applied during the 8-session format of a pilot study with patients diagnosed with major depressive disorder or dysthymia. Finally, feedback was requested from seasoned and highly respected therapists, some of whom were familiar with PCT. According to the mentioned guideline, the intervention manual selected the theoretical framework, in this case PCT, to include its conceptualization of depression and resolution of dilemmas (to foster clinical improvement) as a main treatment goal. The manual was then contrasted with psychoanalytic psychotherapy, cognitive-behavior therapy (CBT), motivational interviewing (MI), and other similar approaches such as cognitive-analytic therapy and coherence therapy. Following these conceptual clarifications, the specific interventions included in the manual were defined according to both categories: their unique and essential components and those conceived as common psychotherapeutic factors. Next, the general structure and content for each session were presented. The structure consisted of seven well-defined individual sessions with an additional session, which could complement any of the former sessions to address the patient's issues in greater depth, if needed. This Dilemma-Focused Intervention manual aimed to improve the treatment outcome for depression by offering an intervention that could be combined with other general approaches. At its present level of definition, it allows for inclusion in controlled trials (eg, the current RCT combining group CBT with this intervention). Thus, this manual added to the existing resources in psychotherapeutic research and practice for treatment of depression.

Pre-irradiation chemotherapy for newly diagnosed high grade astrocytoma.

PubMed

Mathieu, N Tubiana; Genet, D; Labrousse, F; Bouillet, P; Denes, S Lavau; Martin, J; Labourey, J L; Venat, L; Clavere, P; Moreau, J J

2004-01-01

The purpose of this work was to determine the response rate and toxicity of a combination of Carmustine and Cisplatin administered before radiation in patients with newly diagnosed high grade astrocytoma. A good response rate has been published with this association in primary cerebral high grade tumor. This protocol was administered in a homogeneous population of 37 adult patients with measurable tumor on magnetic resonance imaging (MRI) or CT scan. After biopsy or subtotal resection, the patients received BCNU 40 mg/m2/d and CODP 40 mg/m2/d, for 3 days every 28 days for 3 cycles. Evaluation was performed before each cycle. Radiation therapy began 4 weeks after completing the chemotherapy or immediately if there was evidence of tumor progression on chemotherapy. Seven out of 37 (19%) demonstrated tumor regression with a median duration to progression of 11 months. Median survival was 6 months. Myelosuppression was the predominant but manageable toxicity. This work indicated that the first chemotherapy protocol gave poor results in a homogeneous group of patients, with bad prognosis.

The effect of myofascial release and microwave diathermy combined with acupuncture versus acupuncture therapy in tension-type headache patients: A pragmatic randomized controlled trial.

PubMed

Georgoudis, George; Felah, Bledjana; Nikolaidis, Pantelis; Damigos, Dimitrios

2018-04-01

Nonpharmacological therapies for tension-type headache (TTH) and cervicogenic cephalalgia are often a treatment choice, despite the weak to moderate evidence. The aim of this study was to compare the effectiveness of an acupuncture/stretching protocol versus acupuncture/stretching plus physiotherapy techniques, in patients with TTH cephalalgia. A single-blind, prospective, multicentre, randomized controlled trial was designed considering the pragmatic situation of administering such protocols and treating the 44 headache patients participating in this study. The patients were randomly assigned in 2 treatment groups (control group, n = 20, acupuncture/stretching; experimental group, n = 24, acupuncture/stretching plus physiotherapy) and completed 10 treatment sessions within 4 weeks with measurements taking place before treatment, after the fifth treatment and after the 10th treatment. The mechanical pressure pain threshold (PPT) was considered as the main outcome measure, using a mechanical algometer to measure 7 bilateral somatic points. Acupuncture in both groups included 17-20 acupuncture points, whereas stretching was initially taught and subsequently self-administered (self-stretches), following a standardized set of movements of the cervical spine. Physiotherapy consisted of microwave diathermy and myofascial release with hands-on techniques. An improvement was noted in both groups/treatments regarding the main outcome measure PPT, all the way from the first to fifth and the 10th treatment, at all measuring sites and at all measurements in both groups (p < .001). When comparing the 2 groups, differences were noted after the 10th treatment (p < .05). In conclusion, patients with TTH headache were benefited from acupuncture and stretching but further PPT improvements were evidenced when physiotherapy hands-on techniques were added. In clinical terms, the combination of physiotherapy in the form of myofascial release and microwave diathermy with acupuncture and stretching in order to improve the analgesic effect (PPT) is strongly recommended. Copyright © 2017 John Wiley & Sons, Ltd.

Outcome and preferences in female-to-male subjects with gender dysphoria: Experience from Eastern India.

PubMed

Majumder, Anirban; Sanyal, Debmalya

2016-01-01

Awareness of gender dysphoria (GD) and its treatment is increasing. There is paucity of scientific data from India regarding the therapeutic options being used for alleviating GD, which includes psychotherapy, hormone, and surgical treatments. To study the therapeutic options including psychotherapy, hormone, and surgical treatments used for alleviating GD. This is a retrospective study of treatment preferences and outcome in 18 female-to-male (FTM) transgender subjects who presented to the endocrine clinic. The mean follow-up was 1.6 years and only one subject was lost to follow-up after a single visit. All subjects desiring treatment had regular counseling and medical monitoring. All FTM subjects were cross-dressing. Seventeen (94.4%) FTM subjects were receiving cross-sex hormone therapy, in the form of testosterone only (61.1%) or gonadotropin-releasing hormone (GnRH) agonist in combination with testosterone (11.1%) or medroxyprogesterone acetate (MPA) depot in combination with testosterone (22.2%). FTM subjects preferred testosterone or testosterone plus MPA; very few could afford GnRH therapy. Testosterone esters injection was preferred by most (72.2%) subjects as it was most affordable while 22.2% chose 3 monthly injections of testosterone undecanoate for convenience and better symptomatic improvement, but it was more expensive. None preferred testosterone gels because of cost and availability concerns. About 33.3% of our subjects underwent mastectomy, 38.9% had hysterectomy with bilateral salpingo-oophorectomy, and only one subject underwent phalloplasty. About 16.7% of FTM subjects presented with prior mastectomy depicting a high prevalence of unsupervised or poorly supervised surgeries not following protocol wise approach. Notwithstanding of advances in Standards of Care in the Western world, there is lack of awareness and acceptance in the FTM subjects, about proper and timely protocol-wise management options leading to suboptimal physical, social, and sexual results.

Treatment of pleural malignancies by photo-induction combined to systemic chemotherapy: Proof of concept on rodent lung tumors and feasibility study on porcine chest cavities.

PubMed

Wang, Xingyu; Gronchi, Fabrizio; Bensimon, Michael; Mercier, Thomas; Decosterd, Laurent Arthur; Wagnières, Georges; Debefve, Elodie; Ris, Hans-Beat; Letovanec, Igor; Peters, Solange; Perentes, Jean Yannis

2015-12-01

Low-dose, Visudyne®-mediated photodynamic therapy (photo-induction) was shown to selectively enhance tumor vessel transport causing increased uptake of systemically administered chemotherapy in various tumor types grown on rodent lungs. The present experiments explore the efficacy of photo-induced vessel modulation combined to intravenous (IV) liposomal cisplatin (Lipoplatin®) on rodent lung tumors and the feasibility/toxicity of this approach in porcine chest cavities. Three groups of Fischer rats underwent orthotopic sarcoma (n = 14), mesothelioma (n = 14), or adenocarcinoma (n = 12) implantation on the left lung. Half of the animals of each group had photo-induction (0.0625 mg/kg Visudyne®, 10 J/cm(2) ) followed by IV administration of Lipoplatin® (5 mg/kg) and the other half received Lipoplatin® without photo-induction. Then, two groups of minipigs underwent intrapleural thoracoscopic (VATS) photo-induction (0.0625 mg/kg Visudyne®; 30 J/cm(2) hilum; 10 J/cm(2) apex/diaphragm) with in situ light dosimetry in combination with IV Lipoplatin® administration (5 mg/kg). Protocol I (n = 6) received Lipoplatin® immediately after light delivery and Protocol II (n = 9) 90 minutes before light delivery. Three additional animals received Lipoplatin® and VATS pleural biopsies but no photo-induction (controls). Lipoplatin® concentrations were analyzed in blood and tissues before and at regular intervals after photo-induction using inductively coupled plasma mass spectrometry. Photo-induction selectively increased Lipoplatin® uptake in all orthotopic tumors. It significantly increased the ratio of tumor to lung Lipoplatin® concentration in sarcoma (P = 0.0008) and adenocarcinoma (P = 0.01) but not in mesothelioma, compared to IV drug application alone. In minipigs, intrapleural photo-induction combined to systemic Lipoplatin® was well tolerated with no toxicity at 7 days for both treatment protocols. The pleural Lipoplatin® concentrations were not significantly different at 10 and 30 J/cm(2) locations but they were significantly higher in protocol I compared to II (2.37 ± 0.7 vs. 1.37 ± 0.7 ng/mg, P  < 0.001). Visudyne®-mediated photo-induction selectively enhances the uptake of IV administered Lipoplatin® in rodent lung tumors. Intrapleural VATS photo-induction with identical treatment conditions combined to IV Lipoplatin chemotherapy is feasible and well tolerated in a porcine model. Lasers Surg. Med. 47:807-816, 2015. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

Handwriting assessment of Franco-Quebec primary school-age students

PubMed

Couture, Mélanie; Morin, Marie-France; Coallier, Mélissa; Lavigne, Audrey; Archambault, Patricia; Bolduc, Émilie; Chartier, Émilie; Liard, Karolane; Jasmin, Emmanuelle

2016-12-01

Reasons for referring school-age children to occupational therapy mainly relate to handwriting problems. However, there are no validated tools or reference values for assessing handwriting in francophone children in Canada. This study aimed to adapt and validate the writing tasks described in an English Canadian handwriting assessment protocol and to develop reference values for handwriting speed for francophone children. Three writing tasks from the Handwriting Assessment Protocol-2nd Edition (near-point and far-point copying and dictation) were adapted for Québec French children and administered to 141 Grade 1 ( n = 73) and Grade 2 ( n = 68) students. Reference values for handwriting speed were obtained for near point and far point copying tasks. This adapted protocol and these reference values for speed will improve occupational therapy handwriting assessments for the target population.

Myofascial low back pain treatment.

PubMed

Sharan, Deepak; Rajkumar, Joshua Samuel; Mohandoss, Mathankumar; Ranganathan, Rameshkumar

2014-09-01

Myofascial pain is a common musculoskeletal problem, with the low back being one of the commonest affected regions. Several treatments have been used for myofascial low back pain through physical therapies, pharmacologic agents, injections, and other such therapies. This review will provide an update based on recently published literature in the field of myofascial low back pain along with a brief description of a sequenced, multidisciplinary treatment protocol called Skilled Hands-on Approach for the Release of myofascia, Articular, Neural and Soft tissue mobilization (SHARANS) protocol. A comprehensive multidisciplinary approach is recommended for the successful management of individuals with myofascial low back pain.

Protocol for a prospective observational study of conventional treatment and traditional Korean medicine combination treatment for children with cerebral palsy.

PubMed

Yoo, Jeong-Eun; Yun, Young-Ju; Shin, Yong-Beom; Kim, Nam-Kwen; Kim, Soo-Yeon; Shin, Myung-Jun; Yu, Sun-Ae

2016-06-08

Cerebral palsy leads to many complications as well as delayed motor development, and early intensive rehabilitation in infancy, which is based on the theory of brain plasticity, is emphasized. In addition to conventional treatment, including physical, occupational, or speech-language therapies, children also have a demand for traditional Korean medicine interventions such as acupuncture or herbal medicine; however, a lack of evidence has made traditional Korean medicine difficult to implement in practice. We planned a multicentre, prospective, observational study to assess the effectiveness, safety and cost-effectiveness of conventional treatment and traditional Korean medicine combination treatment for children with cerebral palsy. Three hundred children with cerebral palsy aged 6 to 78 months will be recruited from six institutions. Data from each child are collected every month for a one-year period, during which time treatment might be changed or discontinued. A qualified investigator visits the sites to measure effectiveness variables, including Gross Motor Function Measure and Paediatric Evaluation of Disability Inventory. Adverse events and cost-effectiveness variables are collected using surveys conducted at baseline, mid-study, and end of study, as well as monthly tracking surveys. In the analyses, participants will be classified into two groups: group A children will be the conventional treatment group with physical, occupational, speech-language or other conventional rehabilitation therapies, whereas group B children will be the combination treatment group with traditional Korean medicine interventions, that is, herbal medicine, chuna, moxibustion and acupuncture, in addition to conventional treatment. Only a few clinical case reports have evaluated the effectiveness and safety of traditional Korean medicine; therefore, more data are required to provide optimal information to children with cerebral palsy and their guardians. We hypothesized that traditional Korean medicine combination treatment for children with cerebral palsy would have benefits compared with conventional therapy alone. The findings of this study might provide informative data for conducting economic evaluations and developing clinical research on combination treatment for cerebral palsy in South Korea. NCT02223741.

In vivo dosimetry with TLD in conservative treatment of breast cancer patients treated with the EORTC protocol 22881.

PubMed

Hamers, H P; Johansson, K A; Venselaar, J L; de Brouwer, P; Hansson, U; Moudi, C

1993-01-01

Two anthropomorphic phantom breasts and six patients with breast carcinoma were irradiated according the prescriptions of the EORTC protocol 22881 on the conservative management of breast carcinoma by tumorectomy and radiotherapy. During the implantation procedure for an iridium-192 boost, three tubes were implanted, enabling the measurement with TLD rods of the dose within the breasts of the phantom and the patients during one fraction of the external x-ray therapy and during the interstitial therapy. Measured doses were compared with calculated values from a 2-D dose planning system. In general a fair agreement was found between the measured and calculated doses in points within the breast for the external beam therapy as well as for the interstitial treatment.

Treatment of Bulimia Nervosa: Psychological and Psychopharmacologic Considerations.

ERIC Educational Resources Information Center

Phillips, Elaine L.; Greydanus, Donald E.; Pratt, Helen D.; Patel, Dilip R.

2003-01-01

Reviews the current literature on psychological and psychopharmacologic treatments for bulimia nervosa in the adolescent population. Describes the two most researched psychological treatments--cognitive behavior therapy and interpersonal therapy--in terms of treatment protocols and outcome research. Reviews psychopharmacologic treatment, including…

Resource Utilization After Snakebite Severity Score Implementation into Treatment Algorithm of Crotaline Bite.

PubMed

Fowler, Amanda L; Hughes, Darrel W; Muir, Mark T; VanWert, Elizabeth M; Gamboa, Conrado D; Myers, John G

2017-12-01

Crotaline envenomation clinical manifestations vary considerably among patients. Current recommendations for treatment with Crotalidae polyvalent immune Fab require assessment of envenomation control. Determining control of envenomation, particularly when patients are evaluated by different providers in separate clinical settings, can be difficult. To determine if a difference in total vials of Crotalidae antivenin therapy exists between pre-protocol and post-Snakebite Severity Score (SSS) protocol. Retrospective medical record review at an academic medical and regional Level I trauma center. Resource utilization in patients with a diagnosis of "snakebite" was compared between patients treated pre- and post-SSS protocol implementation. One hundred forty-six patients were included in the evaluation. One hundred twenty-seven (87.0%) patients received antivenin, n = 80 (90.9%) in the pre-protocol group and n = 47 (81.0%) in the post-protocol group. Median total number of antivenin vials per patient was lower in the post-protocol group than the pre-protocol group, 16 (10-24 interquartile range) vs. 12 (10-16 interquartile range), p = 0.006. This decreased utilization correlates to an approximate $13,200 savings per patient. Hospital and intensive care unit length of stay, opioid use, incidence of blood product transfusion, need for surgical intervention, or need for intubation were not different between groups. A snakebite protocol with SSS utilization to guide antivenin administration results in significantly decreased antivenin therapy in snakebite patients without increase in other health care utilization. Copyright © 2017 Elsevier Inc. All rights reserved.

Histologic findings in protocol biopsies performed in stable renal allografts under different immunosuppressive schedules.

PubMed

Moreso, F; Alperovich, G; Fulladosa, X; Gil-Vernet, S; Ibernon, M; Carrera, M; Castelao, A M; Hueso, M; Grinyo, J M; Serón, D

2003-08-01

Protocol biopsies performed in stable renal allografts show different degrees of acute and chronic lesions. Histologic findings in protocol biopsies have been related to graft outcome. We evaluated histologic lesions observed in protocol biopsies performed in patients under different immunosuppression therapies. From June 1988 a protocol biopsy was performed at approximately 4 months in patients who fulfilled the following criteria: serum creatinine <300 micromol/L; stable renal function; and proteinuria <1 g/d. Histologic lesions were graded according to 1997 Banff criteria. For the present study we considered the following groups according to immunosuppressive schedule: (i) induction therapy with polyclonal or monoclonal antilymphocytic antibodies associated with cyclosporine and prednisone (n=201); (ii) cyclosporine, mycophenolate mofetil, and prednisone (n=127); and (iii) tacrolimus, mycophenolate mofetil, and prednisone (n=51). On protocol biopsy patients treated with tacrolimus displayed a lower acute score (0.61+/-1.01 vs 1.24+/-1.23 in group I, 1.28+/-1.41 in group II; P<.0001) and a higher proportion of normal biopsies (57.1% vs 41.9% in group I, 45.1% in group II; P=.016). A similar proportion of chronic lesions (chronic score of group I: 1.30+/-1.56; group II: 1.34+/-1.80; group III: 1.51+/-0.95; P=NS) was observed in the three groups. Protocol biopsies displayed fewer acute lesions in patients treated with tacrolimus. This result suggests that the efficacy of new immunosuppression schedules can be evaluated using the protocol biopsy as a surrogate marker of graft outcome.

Aquatic therapy versus conventional land-based therapy for Parkinson's disease: an open-label pilot study.

PubMed

Vivas, Jamile; Arias, Pablo; Cudeiro, Javier

2011-08-01

To assess and compare 2 different protocols of physiotherapy (land or water therapy) for people with Parkinson's disease (PD) focused on postural stability and self-movement, and to provide methodological information regarding progression within the program for a future larger trial. Randomized, controlled, open-label pilot trial. Outpatients, Parkinson's disease Center of Ferrol-Galicia (Spain). Individuals (N=11) with idiopathic PD in stages 2 or 3 according to the Hoehn and Yahr Scale completed the investigation (intervention period plus follow-up). After baseline evaluations, participants were randomly assigned to a land-based therapy (active control group) or a water-based therapy (experimental group). Participants underwent individual sessions for 4 weeks, twice a week, for 45 minutes per session. Both interventions were matched in terms of exercise features, which were structured in stages with clear objectives and progression criteria to pass to the next phase. Participants underwent a first baseline assessment, a posttest immediately after 4 weeks of intervention, and a follow-up assessment after 17 days. Evaluations were performed OFF-dose after withholding medication for 12 hours. Functional assessments included the Functional Reach Test (FRT), the Berg Balance Scale (BBS), the UPDRS, the 5-m walk test, and the Timed Up and Go test. A main effect of both therapies was seen for the FRT. Only the aquatic therapy group improved in the BBS and the UPDRS. In this pilot study, physiotherapy protocols produced improvement in postural stability in PD that was significantly larger after aquatic therapy. The intervention protocols are shown to be feasible and seem to be of value in amelioration of postural stability-related impairments in PD. Some of the methodological aspects detailed here can be used to design larger controlled trials. Copyright © 2011 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Comparison of a CHOP-LAsp-based protocol with and without maintenance for canine multicentric lymphoma.

PubMed

Lautscham, E M; Kessler, M; Ernst, T; Willimzig, L; Neiger, R

2017-03-25

The recommendation to treat canine lymphoma with a discontinuous protocol is based on small case numbers and mostly historic controls. This study compares duration of first remission (DFR) and overall survival time (ST) with a discontinuous protocol to the same protocol with maintenance phase. 408 dogs were treated with a CHOP-LAsp (C=cyclophosphamide; H=hydroxydaunorubicin; O=Oncovin; P=prednisolone; LAsp=l-asparaginase)-based 28-week induction protocol. In 75 dogs (cohort 1), this was followed by a maintenance phase consisting of vincristine, chlorambucil and actinomycin-D with a total treatment duration of two years. In the subsequent 333 dogs, therapy was discontinued after induction (cohort 2). Median DFR and ST in cohort 1 were 216 and 375 days and 184 and 304 days in cohort 2. 6-Month, 1-year and 2-year survival rates in cohort 1 were 73 per cent, 50 per cent, 24 per cent and 67 per cent, 39 per cent, 21 per cent in cohort 2. There was no significant difference between the two protocols (P=0.291 for ST, P=0.071 for DFR). On multivariate analysis, corticosteroid pretreatment (P=0.005), thrombocytopenia at diagnosis (P=0.019), stage (P=0.009), substage b at relapse (P<0.001), age (P=0.002) and incomplete or unstable remission necessitating intensification of therapy (P=0.004) were negatively correlated with ST in both groups. This study supports the use of a discontinuous protocol for canine multicentric lymphoma. British Veterinary Association.

Prevention of Iron Overload and Long Term Maintenance of Normal Iron Stores in Thalassaemia Major Patients using Deferiprone or Deferiprone Deferoxamine Combination.

PubMed

Kolnagou, Annita; Kontoghiorghe, Christina N; Kontoghiorghes, George J

2017-07-01

Decrease in mortality and morbidity is observed in thalassaemia major patients with reduced iron load in comparison to heavy iron loaded patients. Effective and complete treatment of transfusional iron overload can be achieved by chelation protocols that can eliminate excess iron and maintain normal iron stores (NIS). The maintenance of NIS, i. e., serum ferritin (350 μg/L >), MRI T2* cardiac (>20 ms) and liver (>6.3 ms) relaxation time levels was monitored in 16 thalassaemia major patients (32-53 years, 12 splenectomized, 10 male, erythrocyte transfusions 120-323 ml/kg/year) for about 90 patient years. The patients were treated with individualised tailor-made deferiprone or deferiprone/deferoxamine combination protocols. In 8 patients deferiprone (50-100 mg/kg/day) was sufficient for maintaining NIS and withdrawal of deferiprone for 28 months in total was necessary in 4 patients for preventing iron deficiency. In 3 other patients intermittent deferoxamine (50-75 mg/kg/8-30 h, 1-4 days/week) in combination with deferiprone (75-100 mg/kg/day) was sufficient for maintaining NIS. In the remaining 5 patients deferiprone (75-100 mg/kg/day) and deferoxamine (50-60 mg/kg/8-15 h, 1-7 days/week) combination was used for maintaining NIS, as a result of increased transfusions which were caused mainly by splenomegaly and infections. No toxic side effects were detected during the study. Lower chelation doses were used for the maintenance of NIS in comparison to iron loaded categories of patients. The safe maintenance of NIS using deferiprone and deferiprone/deferoxamine combinations should be considered as an optimum therapy for the complete treatment of iron overload in the majority of thalassaemia patients. © Georg Thieme Verlag KG Stuttgart · New York.

GENERIC VERIFICATION PROTOCOL: DISTRIBUTED GENERATION AND COMBINED HEAT AND POWER FIELD TESTING PROTOCOL

EPA Science Inventory

This report is a generic verification protocol by which EPA’s Environmental Technology Verification program tests newly developed equipment for distributed generation of electric power, usually micro-turbine generators and internal combustion engine generators. The protocol will ...

A randomized trial of immunotherapy for persistent genital warts

PubMed Central

Jardine, David; Lu, Jieqiang; Pang, James; Palmer, Cheryn; Tu, Quanmei; Chuah, John; Frazer, Ian H.

2012-01-01

Aim To determine whether immunotherapy with HPV6 L1 virus like particles (VLPs) without adjuvant (VLP immunotherapy) reduces recurrence of genital warts following destructive therapy. Trial design A randomized placebo controlled blinded study of treatment of recurrent genital warts amenable to destructive therapy, conducted independently in Australia and China. Methods Patients received conventional destructive therapy of all evident warts together with intramuscular administration of 1, 5 or 25 µg of VLP immunotherapy, or of placebo immunotherapy (0.9% NaCl), as immunotherapy at week 0 and week 4. Primary outcome, assessed at week 8, was recurrence of visible warts. Results Of 33 protocol compliant Brisbane recipients of placebo immunotherapy, 11 were disease free at two months, and a further 9 demonstrated reduction of > 50% in total wart area. Wart area reduction following destructive treatment correlated with prior duration of disease. Among 102 protocol compliant Brisbane recipients of VLP immunotherapy, disease reduction was significantly greater than among the placebo immunotherapy (50% ± s.e.m. 7%) recipients for subjects receiving 5 µg or 25 µg of VLP immunotherapy/dose (71% ± s.e.m.7%) but not for those receiving 1 µg VLP immunotherapy/dose (42% ± 7%). Of 52 protocol compliant placebo immunotherapy recipients in Wenzhou, 37 were disease free at two months, and a further 8 had > 50% disease reduction. Prior disease duration was much shorter in Wenzhou subject (8.1 ± 1.1 mo) than in Brisbane subjects (53.7 ± 5.5 mo). No significant reduction in mean wart area was observed for the 168 Wenzhou protocol compliant subjects who also received VLP immunotherapy. Conclusions This study confirms the findings in a previous open label trial that administration of VLP immunotherapy may assist in clearance of recurrent genital warts in patients for whom destructive therapy is unsuccessful and that unsuccessful destructive therapy is more common with increasing prior disease duration. PMID:22634446

Extracorporeal shock wave therapy for the treatment of chronic plantar fasciitis: indications, protocol, intermediate results, and a comparison of results to fasciotomy.

PubMed

Weil, Lowell Scott; Roukis, Thomas S; Weil, Lowell Scott; Borrelli, Anthony H

2002-01-01

A review of the history, mechanism of action, and application of extracorporeal shock wave therapy for chronic plantar fasciitis is presented. The results of 40 feet treated with this modality are reviewed after a mean follow-up time of 8.4 months. All procedures were performed under intravenous sedation and local infiltrative anesthesia. An electrohydraulic shock wave with a mean of 20.6 kV combined with a mean of 2,506 pulses was used. The results of a similar demographic class of patients having undergone a percutaneous plantar fasciotomy at our institution were compared to the results of this cohort of shock wave patients. Eighty-two percent of the patients treated with extracorporeal shock wave therapy were successfully treated as compared to 83% with a percutaneous plantar fasciotomy. The mean score on the 11-point visual analog scale for satisfied patients was 7.9 preoperatively and 2.95 within 7 days postoperatively. After 3 months, the mean visual analog score was 4.2 or 50% of the preoperative value after a mean of 8.4 months following treatment. Eighty-three percent of the patients treated stated that shock wave therapy improved their symptoms. There were no complications encountered in any patient in this study. Extracorporeal shock wave therapy is an effective treatment, which significantly reduces the symptoms associated with chronic plantar fasciitis and compares favorably to the results achieved with surgical intervention in the form of a percutaneous plantar fasciotomy.

Analysis of Variability in Intraoperative Fluid Administration for Colorectal Surgery: An Argument for Goal-Directed Fluid Therapy.

PubMed

Quinn, Timothy D; Brovman, Ethan Y; Urman, Richard D

2017-09-01

Fluid therapy in the perioperative period varies greatly between anesthesia providers and may have a negative impact on surgical outcomes. We conducted a retrospective analysis of 705 elective colorectal cases consisting of colectomies, ileocolic resections, and low anterior resections at an academic institution from January 1, 2010 to May 29, 2015, collected by our electronic medical record before implementation of Enhanced Recovery After Surgery (ERAS ® ) pathways. The mean for total crystalloid administration was 2578 mL with a standard deviation (SD) that was approximately 50% of the mean value. A combination of both normal saline and lactated Ringer's solution was used in almost all cases without a clear rationale for fluid choice. Fluid administered to patients was disproportional to measured intraoperative fluid losses (estimated blood loss and urine output) by a factor of 10. The average rate of fluid given was 1050 mL/h with an SD of nearly the same amount (951 mL). There was a variability of over 67% in total crystalloid administered based on both ideal body weight and total body weight. We found that a wide variability in the amount and type of fluid therapy administered existed at our institution before implementation of a colorectal ERAS pathway or routine use of goal-directed fluid therapy (GDFT). ERAS pathways with GDFT protocols could lead to more rational and consistent fluid therapy leading to improved outcomes.

Utility of bortezomib retreatment in relapsed or refractory multiple myeloma patients: a multicenter case series.

PubMed

Wolf, Jeffrey; Richardson, Paul G; Schuster, Michael; LeBlanc, Annette; Walters, Ian B; Battleman, David S

2008-10-01

Bortezomib therapy has become an important part of the standard of care for patients with relapsed multiple myeloma, and preliminary clinical evidence suggests that bortezomib retreatment in patients previously treated with the drug may prolong disease control. This retrospective study was designed to clarify the utility of bortezomib as a repeat therapy. We reviewed records from 3 major cancer centers that had participated in the phase II (SUMMIT or CREST) or phase III (APEX) registration studies to identify patients who were subsequently retreated off protocol with bortezomib-based therapy. We found 22 patients who received bortezomib retreatment following a 60 or more day gap between bortezomib treatments. Twelve patients had intervening therapy between initial bortezomib treatment and bortezomib retreatment. During retreatment, 14 of 22 patients received bortezomib in combination with another antineoplastic agent. The overall response rate for bortezomib retreatment was 50% (9% complete responses). The median length of retreatment was 5.1 months in responding patients and 2.4 months in nonresponding patients. Therapy was terminated due to unmanageable toxicity in 2 patients during retreatment, compared with 6 patients during initial treatment. During retreatment, no patients required dose reduction due to peripheral neuropathy, compared to 4 patients during their initial treatment. Thus, bortezomib retreatment appears to be safe and effective. Favorable observed response rates with bortezomib retreatment suggest that it may be a viable option for relapsed or refractory multiple myeloma, even in patients previously exposed to bortezomib.

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

How Effective Are Percutaneous Liver-Directed Therapies in Patients with Non-Colorectal Liver Metastases?

PubMed Central

Vogl, Thomas J.; Emam, Ahmed; Naguib, Nagy N.; Eichler, Katrin; Zangos, Stefan

2015-01-01

Summary Background The purpose of this review is to demonstrate the clinical indications, technical developments, and outcome of liver-directed therapies in interventional oncology of non-colorectal liver metastases. Methods Liver-directed therapies are classified into vascular transarterial techniques such as chemoperfusion (TACP), chemoembolization (TACE), radioembolization (selective internal radiation therapy (SIRT)), and chemosaturation, as well as thermal ablation techniques like microwave ablation (MWA), radiofrequency ablation (RFA), laser-induced thermotherapy (LITT), cryotherapy, and irreversible electroporation (IRE). The authors searched the database PubMed using the following terms: ‘image-guided tumor ablation’, ‘thermal ablation therapies’, ‘liver metastases of uveal melanoma’, ‘neuroendocrine carcinoma’, ‘breast cancer’, and ‘non-colorectal liver metastases’. Results Various combinations of the above-mentioned therapy protocols are possible. In neuroendocrine carcinomas, oligonodular liver metastases are treated successfully via thermal ablation like RFA, LITT, or MWA, and diffuse involvement via TACE or SIRT. Although liver involvement in breast cancer is a systemic disease, non-responding nodular metastases can be controlled via RFA or LITT. In ocular or cutaneous melanoma, thermal ablation is rarely considered as an interventional treatment option, as opposed to TACE, SIRT, or chemosaturation. Rarely liver-directed therapies are used in pancreatic cancer, most likely due to problems such as biliary digestive communications after surgery and the risk of infections. Rare indications for thermal ablation are liver metastases of other primary cancers like non-small cell lung, gastric, and ovarian cancer. Conclusion Interventional oncological techniques play a role in patients with liver-dominant metastases. PMID:26889144

Stem cells for amyotrophic lateral sclerosis modeling and therapy: myth or fact?

PubMed

Coatti, G C; Beccari, M S; Olávio, T R; Mitne-Neto, M; Okamoto, O K; Zatz, M

2015-03-01

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease whose pathophysiology is poorly understood. Aiming to better understand the cause of motor neuron death, the use of experimental cell-based models increased significantly over the past years. In this scenario, much knowledge has been generated from the study of motor neurons derived from embryonic stem cells and induced pluripotent stem cells. These methods, however, have advantages and disadvantages, which must be balanced on experimental design. Preclinical studies provide valuable information, making it possible to combine diverse methods to build an expanded knowledge of ALS pathophysiology. In addition to using stem cells as experimental models for understanding disease mechanism, these cells had been quoted for therapy in ALS. Despite ethical issues involved in its use, cell therapy with neural stem cells stands out. A phase I clinical trial was recently completed and a phase II is on its way, attesting the method's safety. In another approach, mesenchymal stromal cells capable of releasing neuroregulatory and anti-inflammatory factors have also been listed as candidates for cell therapy for ALS, and have been admitted as safe in a phase I trial. Despite recent advances, application of stem cells as an actual therapy for ALS patients is still in debate. Here, we discuss how stem cells have been useful in modeling ALS and address critical topics concerning their therapeutic use, such as administration protocols, injection site, cell type to be administered, type of transplantation (autologous vs. allogeneic) among other issues with particular implications for ALS therapy. © 2015 International Society for Advancement of Cytometry.

The bipolarity of light and dark: A review on Bipolar Disorder and circadian cycles.

PubMed

Abreu, T; Bragança, M

2015-10-01

Bipolar Disorder is characterized by episodes running the full mood spectrum, from mania to depression. Between mood episodes, residual symptoms remain, as sleep alterations, circadian cycle disturbances, emotional deregulation, cognitive impairment and increased risk for comorbidities. The present review intends to reflect about the most recent and relevant information concerning the biunivocal relation between bipolar disorder and circadian cycles. It was conducted a literature search on PubMed database using the search terms "bipolar", "circadian", "melatonin", "cortisol", "body temperature", "Clock gene", "Bmal1 gene", "Per gene", "Cry gene", "GSK3β", "chronotype", "light therapy", "dark therapy", "sleep deprivation", "lithum" and "agomelatine". Search results were manually reviewed, and pertinent studies were selected for inclusion as appropriate. Several studies support the relationship between bipolar disorder and circadian cycles, discussing alterations in melatonin, body temperature and cortisol rhythms; disruption of sleep/wake cycle; variations of clock genes; and chronotype. Some therapeutics for bipolar disorder directed to the circadian cycles disturbances are also discussed, including lithium carbonate, agomelatine, light therapy, dark therapy, sleep deprivation and interpersonal and social rhythm therapy. This review provides a summary of an extensive research for the relevant literature on this theme, not a patient-wise meta-analysis. In the future, it is essential to achieve a better understanding of the relation between bipolar disorder and the circadian system. It is required to establish new treatment protocols, combining psychotherapy, therapies targeting the circadian rhythms and the latest drugs, in order to reduce the risk of relapse and improve affective behaviour. Copyright © 2015 Elsevier B.V. All rights reserved.

Seasonal heat stress: Clinical implications and hormone treatments for the fertility of dairy cows.

PubMed

De Rensis, F; Garcia-Ispierto, I; López-Gatius, F

2015-09-15

Heat stress has consequences on both the physiology and reproductive performance of cows, but the most dramatic effect for dairy producers is the decrease produced in fertility. The effects of heat stress on fertility include an increased number of days open, reduced conception rate, and larger number of cows suffering different types of anestrus. Once becomes pregnant, heat stress affects also the reproductive success of the cow through its direct effects on the ovary, uterus, gametes, embryo, and early fetus. This article reviews current knowledge of the effects of heat stress on fertility in dairy cows and the hormonal strategies used to mitigate these effects at the farm level. Administration of GnRH at the moment of artificial insemination can improve the conception rate. Breeding synchronization protocols for fixed-time insemination may reduce the calving conception interval and the number of services per conception. Progesterone-based protocols seem resolve better the reproductive disorders related to a hot environment (anestrus) than GnRH-based protocols. The use of combinations of GnRH, eCG, and hCG in progesterone-based protocols can improve results. Progesterone supplementation during the late embryonic and/or early fetal period would be useful in curtailing pregnancy losses, mainly in single pregnancies, whereas a more positive effect of treatment with GnRH than progesterone has been found in twin pregnancies. Melatonin therapy is emerging as a promising strategy to improve the natural reproductive performance of cows suffering conditions of heat stress. Copyright © 2015 Elsevier Inc. All rights reserved.

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