Randomized Controlled Trials in Music Therapy: Guidelines for Design and Implementation.

PubMed

Bradt, Joke

2012-01-01

Evidence from randomized controlled trials (RCTs) plays a powerful role in today's healthcare industry. At the same time, it is important that multiple types of evidence contribute to music therapy's knowledge base and that the dialogue of clinical effectiveness in music therapy is not dominated by the biomedical hierarchical model of evidence-based practice. Whether or not one agrees with the hierarchical model of evidence in the current healthcare climate, RCTs can contribute important knowledge to our field. Therefore, it is important that music therapists are prepared to design trials that meet current methodological standards and, equally important, are able to respond appropriately to those design aspects that may not be feasible in music therapy research. To provide practical guidelines to music therapy researchers for the design and implementation of RCTs as well as to enable music therapists to be well-informed consumers of RCT evidence. This article reviews key design aspects of RCTs and discusses how to best implement these standards in music therapy trials. A systematic presentation of basic randomization methods, allocation concealment strategies, issues related to blinding in music therapy trials and strategies for implementation, the use of treatment manuals, types of control groups, outcome selection, and sample size computation is provided. Despite the challenges of meeting all key design demands typical of an RCT, it is possible to design rigorous music therapy RCTs that accurately estimate music therapy treatment benefits.

Immunotherapy for non-small cell lung cancer: current concepts and clinical trials

PubMed Central

Mayor, Marissa; Yang, Neng; Sterman, Daniel; Jones, David R.; Adusumilli, Prasad S.

2016-01-01

Recent successes in immunotherapeutic strategies are being investigated to combat cancers that have less than ideal responses to standard of care treatment, such as non-small-cell lung cancer. In this paper, we summarize concepts and the current status of immunotherapy for non-small cell lung cancer, including salient features of the major categories of immunotherapy—monoclonal antibody therapy, immune checkpoint blockade, immunotoxins, anticancer vaccines, and adoptive cell therapy. PMID:26516195

Dual Therapy Treatment Strategies for the Management of Patients Infected with HIV: A Systematic Review of Current Evidence in ARV-Naive or ARV-Experienced, Virologically Suppressed Patients.

PubMed

Baril, Jean-Guy; Angel, Jonathan B; Gill, M John; Gathe, Joseph; Cahn, Pedro; van Wyk, Jean; Walmsley, Sharon

2016-01-01

We reviewed the current literature regarding antiretroviral (ARV)-sparing therapy strategies to determine whether these novel regimens can be considered appropriate alternatives to standard regimens for the initial treatment of ARV-naive patients or as switch therapy for those patients with virologically suppressed HIV infection. A search for studies related to HIV dual therapy published from January 2000 through April 2014 was performed using Biosis, Derwent Drug File, Embase, International Pharmaceutical Abstracts, Medline, Pascal, SciSearch, and TOXNET databases; seven major trial registries, and the abstracts of major conferences. Using predetermined criteria for inclusion, an expert review committee critically reviewed and qualitatively evaluated all identified trials for efficacy and safety results and potential limitations. Sixteen studies of dual therapy regimens were critiqued for the ARV-naive population. Studies of a protease inhibitor/ritonavir in combination with the integrase inhibitor raltegravir or the nucleoside reverse transcriptase inhibitor lamivudine provided the most definitive evidence supporting a role for dual therapy. In particular, lopinavir/ritonavir or darunavir/ritonavir combined with raltegravir and lopinavir/ritonavir combined with lamivudine demonstrated noninferiority to standard of care triple therapy after 48 weeks of treatment. Thirteen trials were critiqued in ARV-experienced, virologically suppressed patients. The virologic efficacy outcomes were mixed. Although overall data regarding toxicity are limited, when compared with standard triple therapy, certain dual therapy regimens may offer advantages in renal function, bone mineral density, and limb fat changes; however, some dual combinations may elevate lipid or bilirubin levels. The potential benefits of dual therapy regimens include reduced toxicity, improved tolerability and adherence, and reduced cost. Although the data reviewed here provide valuable insights into the effectiveness and tolerability of dual therapy regimens, it remains unclear whether these potential benefits can be maintained long-term. Appropriately powered studies with longer follow-up periods are needed to more definitively assess potential toxicity reduction advantages with dual therapy.

The Economic Impact of Closed-Incision Negative-Pressure Therapy in High-Risk Abdominal Incisions: A Cost-Utility Analysis.

PubMed

Chopra, Karan; Gowda, Arvind U; Morrow, Chris; Holton, Luther; Singh, Devinder P

2016-04-01

Complex abdominal wall reconstruction is beset by postoperative complications. A recent meta-analysis comparing the use of closed-incision negative-pressure therapy to standard dressings found a statistically significant reduction in surgical-site infection. The use of closed-incision negative-pressure therapy is gaining acceptance in this population; however, the economic impact of this innovative dressing remains unknown. In this study, a cost-utility analysis was performed assessing closed-incision negative-pressure therapy and standard dressings following closure of abdominal incisions in high-risk patients. Cost-utility methodology involved reviewing literature related to closed-incision negative-pressure therapy in abdominal wall surgery, obtaining utility estimates to calculate quality-adjusted life-year scores for successful surgery and surgery complicated by surgical-site infection, summing costs using Medicare Current Procedural Terminology codes, and creating a decision tree illuminating the most cost-effective dressing strategy. One-way sensitivity analysis was performed to assess the robustness of the results. The aforementioned meta-analysis comparing closed-incision negative-pressure therapy to standard dressings included a subset of five studies assessing abdominal wall surgery in 829 patients (260 closed-incision negative-pressure therapy and 569 standard dressings). Decision tree analysis revealed an estimated savings of $1546.52 and a gain of 0.0024 quality-adjusted life-year with closed-incision negative-pressure therapy compared with standard dressings; therefore, closed-incision negative-pressure therapy is a dominant treatment strategy. One-way sensitivity analysis revealed that closed-incision negative-pressure therapy is a cost-effective option when the surgical-site infection rate is greater than 16.39 percent. The use of closed-incision negative-pressure therapy is cost-saving following closure of abdominal incisions in high-risk patients.

Gastrointestinal Stromal Tumors: Management of metastatic disease and emerging therapies

PubMed Central

Vadakara, Joseph

2013-01-01

Synopsis Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors of the gastrointestinal tract. Prior to the advent of tyrosine kinase inhibitors like imatinib, there were few treatment options available to patients with metastatic GIST. Surgery was the mainstay of treatment and the prognosis for patients with metastatic GIST was dismal. With the advent of imatinib the prognosis of metastatic GIST has improved dramatically. Second line tyrosine kinase inhibitors (TKI) such as sunitinib and regorafenib have further bettered prognosis, however there is still a need for therapies for patients with disease refractory to TKI therapy. Newer agents such as the Hsp90 inhibitors, PI3K-AKT-mTOR inhibitors and IGF1-R inhibitors are currently under investigation and may have promise. This review discusses the current standard of care in terms of pharmacotherapy, both standard and investigational (summarized in Box 1), in the management of metastatic GIST. PMID:24093167

Endoscopic management of benign bile duct strictures.

PubMed

Baron, Todd H; Davee, Tomas

2013-04-01

The use of endoscopic retrograde cholangiopancreatography for treating benign biliary strictures has become the standard of practice, with surgery and percutaneous therapy reserved for selected patients. The gold-standard endoscopic therapy is dilation of the stricture followed by placing and exchanging progressively larger and more numerable plastic stents over a 1-year period. Newer modalities, including the use of fully covered metal stents, are currently under investigation in an effort to improve the treatment of benign biliary strictures. Copyright © 2013 Elsevier Inc. All rights reserved.

Radiation techniques for esophageal cancer.

PubMed

Zhang, Minsi; Wu, Abraham J

2017-10-01

Radiotherapy plays a crucial role in the curative management of localized esophageal cancer, both as definitive and preoperative therapy. For definitive therapy, the standard radiation dose is 50.4 Gy in 28 fractions and should be delivered with concurrent chemotherapy. Chemoradiotherapy also has a wellestablished benefit in the preoperative setting, as established in the CROSS randomized trial. Radiation fields are typically generous, to account for subclinical extension of disease along the esophagus and to regional nodes. Three-dimensional conformal radiation is the current standard technique for esophageal cancer, though intensity-modulated radiation therapy is increasingly utilized and may improve the outcomes of esophageal radiotherapy by reducing radiation dose to critical normal tissues.

Multiple imputation to account for measurement error in marginal structural models

PubMed Central

Edwards, Jessie K.; Cole, Stephen R.; Westreich, Daniel; Crane, Heidi; Eron, Joseph J.; Mathews, W. Christopher; Moore, Richard; Boswell, Stephen L.; Lesko, Catherine R.; Mugavero, Michael J.

2015-01-01

Background Marginal structural models are an important tool for observational studies. These models typically assume that variables are measured without error. We describe a method to account for differential and non-differential measurement error in a marginal structural model. Methods We illustrate the method estimating the joint effects of antiretroviral therapy initiation and current smoking on all-cause mortality in a United States cohort of 12,290 patients with HIV followed for up to 5 years between 1998 and 2011. Smoking status was likely measured with error, but a subset of 3686 patients who reported smoking status on separate questionnaires composed an internal validation subgroup. We compared a standard joint marginal structural model fit using inverse probability weights to a model that also accounted for misclassification of smoking status using multiple imputation. Results In the standard analysis, current smoking was not associated with increased risk of mortality. After accounting for misclassification, current smoking without therapy was associated with increased mortality [hazard ratio (HR): 1.2 (95% CI: 0.6, 2.3)]. The HR for current smoking and therapy (0.4 (95% CI: 0.2, 0.7)) was similar to the HR for no smoking and therapy (0.4; 95% CI: 0.2, 0.6). Conclusions Multiple imputation can be used to account for measurement error in concert with methods for causal inference to strengthen results from observational studies. PMID:26214338

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

PubMed

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

2012-06-01

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

Hyperhidrosis: review of recent advances and new therapeutic options for primary hyperhidrosis.

PubMed

Brown, Ashley L; Gordon, Jennifer; Hill, Samantha

2014-08-01

Primary focal hyperhidrosis is a common condition that negatively impacts quality of life for many pediatric patients and can be challenging to treat. Standard treatments for hyperhidrosis can be used with success in many patients, and newer therapies and techniques offer options that have demonstrated efficacy and safety. This review highlights standard therapies for primary focal hyperhidrosis as well as the most recent technique advancements and alternative treatment options. The standard approach to treating primary focal hyperhidrosis remains initiation of topical preparations, followed by advancement to systemic medications, local administration of medication and/or surgical procedures. Recent studies focus on enhancing tolerability of topical preparations as well as evaluating the efficacy of neuromodulator injections, oral anticholinergic medications and laser therapy. Microwave technology has also been introduced for the treatment of focal hyperhidrosis with promising results. Many therapies exist for hyperhidrosis, and each treatment plan must be evaluated on a patient-by-patient basis. Advances in standard therapies and emergence of new treatment techniques are the main emphases of current published literature on hyperhidrosis. This article presents recent therapeutic options as well as updates on more established strategies to help practitioners treat this challenging condition.

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

Supanich, M.

The International Electrotechnical Commission (IEC) writes standards that manufacturers of electrical equipment must comply with. Medical electrical equipment, such as medical imaging, radiation therapy, and radiation dosimetry devices, fall under Technical Committee 62. Of particular interest to medical physicists are the standards developed within Subcommittees (SC) 62B, which addresses diagnostic radiological imaging equipment, and 62C, which addresses equipment for radiation therapy, nuclear medicine and dosimetry. For example, a Working Group of SC 62B is responsible for safety and quality assurance standards for CT scanners and a Working Group of SC 62C is responsible for standards that set requirements for dosimetricmore » safety and accuracy of linacs and proton accelerators. IEC standards thus have an impact on every aspect of a medical physicist’s job, including equipment testing, shielding design, room layout, and workflow. Consequently, it is imperative that US medical physicists know about existing standards, as well as have input on those under development or undergoing revision. The structure of the IEC and current standards development work will be described in detail. The presentation will explain how US medical physicists can learn about IEC standards and contribute to their development. Learning Objectives: Learn about the structure of the IEC and the influence that IEC standards have on the design of equipment for radiology and radiation therapy. Learn about the mechanisms by which the US participates in the development and revision of standards. Understand the specific requirements of several standards having direct relevance to diagnostic and radiation therapy physicists.« less

Current Therapy of Acquired Ocular Toxoplasmosis: A Review.

PubMed

Lima, Guilherme Sturzeneker Cerqueira; Saraiva, Patricia Grativol Costa; Saraiva, Fábio Petersen

2015-11-01

Caused by the parasite Toxoplasma gondii, ocular toxoplasmosis (OT) is the most common form of posterior infectious uveitis. Combined antiparasitic therapy is the standard treatment for OT, but several other schemes have been proposed. The purpose of the present study was to review the literature on the treatment of OT and provide ophthalmologists with up-to-date information to help reduce OT-related visual morbidity. In conclusion, no ideal treatment scheme was identified; currently prescribed therapeutic schemes yield statistically similar functional outcomes.

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

PubMed Central

Degli Stefani, Mario; Biasutti, Michele

2016-01-01

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

Localized renal cell carcinoma management: an update.

PubMed

Heldwein, Flavio L; McCullough, T Casey; Souto, Carlos A V; Galiano, Marc; Barret, Eric

2008-01-01

To review the current modalities of treatment for localized renal cell carcinoma. A literature search for keywords: renal cell carcinoma, radical nephrectomy, nephron sparing surgery, minimally invasive surgery, and cryoablation was performed for the years 2000 through 2008. The most relevant publications were examined. New epidemiologic data and current treatment of renal cancer were covered. Concerning the treatment of clinically localized disease, the literature supports the standardization of partial nephrectomy and laparoscopic approaches as therapeutic options with better functional results and oncologic success comparable to standard radical resection. Promising initial results are now available for minimally invasive therapies, such as cryotherapy and radiofrequency ablation. Active surveillance has been reported with acceptable results, including for those who are poor surgical candidates. This review covers current advances in radical and conservative treatments of localized kidney cancer. The current status of nephron-sparing surgery, ablative therapies, and active surveillance based on natural history has resulted in great progress in the management of localized renal cell carcinoma.

Atopic dermatitis phenotypes and the need for personalized medicine

PubMed Central

Cabanillas, Beatriz; Brehler, Ann-Christin; Novak, Natalija

2017-01-01

Purpose of review To describe recent developments in therapies which target the molecular mechanisms in atopic dermatitis. Recent findings Current advances in the understanding of the molecular basis of atopic dermatitis are leading to the stratification of different atopic dermatitis phenotypes. New therapies offer the option to target-specific molecules involved in the pathophysiology of atopic dermatitis. Current new therapies under investigation aim to modulate specific inflammatory pathways associated with distinctive atopic dermatitis phenotypes, which would potentially translate into the development of personalized, targeted-specific treatments of atopic dermatitis. Summary Despite the unmet need for well tolerated, effective, and personalized treatment of atopic dermatitis, the current standard treatments of atopic dermatitis do not focus on the individual pathogenesis of the disease. The development of targeted, phenotype-specific therapies has the potential to open a new promising era of individualized treatment of atopic dermatitis. PMID:28582322

Default-Mode Network Functional Connectivity in Aphasia: Therapy-Induced Neuroplasticity

ERIC Educational Resources Information Center

Marcotte, Karine; Perlbarg, Vincent; Marrelec, Guillaume; Benali, Habib; Ansaldo, Ana Ines

2013-01-01

Previous research on participants with aphasia has mainly been based on standard functional neuroimaging analysis. Recent studies have shown that functional connectivity analysis can detect compensatory activity, not revealed by standard analysis. Little is known, however, about the default-mode network in aphasia. In the current study, we studied…

Probiotics in Helicobacter pylori eradication therapy: A systematic review and meta-analysis

PubMed Central

Zhang, Min-Min; Qian, Wei; Qin, Ying-Yi; He, Jia; Zhou, Yu-Hao

2015-01-01

AIM: To summarize the evidence from randomized controlled trials (RCTs) regarding the effect of probiotics by using a meta-analytic approach. METHODS: In July 2013, we searched PubMed, EMBASE, Ovid, the Cochrane Library, and three Chinese databases (Chinese Biomedical Literature Database, Chinese Medical Current Content, and Chinese Scientific Journals database) to identify relevant RCTs. We included RCTs investigating the effect of a combination of probiotics and standard therapy (probiotics group) with standard therapy alone (control group). Risk ratios (RRs) were used to measure the effect of probiotics plus standard therapy on Helicobacter pylori (H. pylori) eradication rates, adverse events, and patient compliance using a random-effect model. RESULTS: We included data on 6997 participants from 45 RCTs, the overall eradication rates of the probiotic group and the control group were 82.31% and 72.08%, respectively. We noted that the use of probiotics plus standard therapy was associated with an increased eradication rate by per-protocol set analysis (RR = 1.11; 95%CI: 1.08-1.15; P < 0.001) or intention-to-treat analysis (RR = 1.13; 95%CI: 1.10-1.16; P < 0.001). Furthermore, the incidence of adverse events was 21.44% in the probiotics group and 36.27% in the control group, and it was found that the probiotics plus standard therapy significantly reduced the risk of adverse events (RR = 0.59; 95%CI: 0.48-0.71; P < 0.001), which demonstrated a favorable effect of probiotics in reducing adverse events associated with H. pylori eradication therapy. The specific reduction in adverse events ranged from 30% to 59%, and this reduction was statistically significant. Finally, probiotics plus standard therapy had little or no effect on patient compliance (RR = 0.98; 95%CI: 0.68-1.39; P = 0.889). CONCLUSION: The use of probiotics plus standard therapy was associated with an increase in the H. pylori eradication rate, and a reduction in adverse events resulting from treatment in the general population. However, this therapy did not improve patient compliance. PMID:25892886

A Methodological Analysis of Randomized Clinical Trials of Computer-Assisted Therapies for Psychiatric Disorders: Toward Improved Standards for an Emerging Field

PubMed Central

Kiluk, Brian D.; Sugarman, Dawn E.; Nich, Charla; Gibbons, Carly J.; Martino, Steve; Rounsaville, Bruce J.; Carroll, Kathleen M.

2013-01-01

Objective Computer-assisted therapies offer a novel, cost-effective strategy for providing evidence-based therapies to a broad range of individuals with psychiatric disorders. However, the extent to which the growing body of randomized trials evaluating computer-assisted therapies meets current standards of methodological rigor for evidence-based interventions is not clear. Method A methodological analysis of randomized clinical trials of computer-assisted therapies for adult psychiatric disorders, published between January 1990 and January 2010, was conducted. Seventy-five studies that examined computer-assisted therapies for a range of axis I disorders were evaluated using a 14-item methodological quality index. Results Results indicated marked heterogeneity in study quality. No study met all 14 basic quality standards, and three met 13 criteria. Consistent weaknesses were noted in evaluation of treatment exposure and adherence, rates of follow-up assessment, and conformity to intention-to-treat principles. Studies utilizing weaker comparison conditions (e.g., wait-list controls) had poorer methodological quality scores and were more likely to report effects favoring the computer-assisted condition. Conclusions While several well-conducted studies have indicated promising results for computer-assisted therapies, this emerging field has not yet achieved a level of methodological quality equivalent to those required for other evidence-based behavioral therapies or pharmacotherapies. Adoption of more consistent standards for methodological quality in this field, with greater attention to potential adverse events, is needed before computer-assisted therapies are widely disseminated or marketed as evidence based. PMID:21536689

Locally advanced rectal cancer: time for precision therapeutics.

PubMed

Weiser, Martin R; Zhang, Zhen; Schrag, Deborah

2015-01-01

The year 2015 marks the 30th anniversary of the publication of NSABP-R01, a landmark trial demonstrating the benefit of adding pelvic radiation to the treatment regimen for locally advanced rectal cancer with a resultant decrease in local recurrence from 25% to 16%. These results ushered in the era of multimodal therapy for rectal cancer, heralding modern treatment and changing the standard of care in the United States. We have seen many advances over the past 3 decades, including optimization of the administration and timing of radiation, widespread adoption of total mesorectal excision (TME), and the implementation of more effective systemic chemotherapy. The current standard is neoadjuvant chemoradiation with 5-fluorouracil (5-FU) and a radiosensitizer, TME, and adjuvant chemotherapy including 5-FU and oxaliplatin. The results of this regimen have been impressive, with a reported local recurrence rate of less than 10%. However, the rates of distant relapse remain 30% to 40%, indicating room for improvement. In addition, trimodality therapy is arduous and many patients are unable to complete the full course of treatment. In this article we discuss the current standard of care and alternative strategies that have evolved in an attempt to individualize therapy according to risk of recurrence.

Dialectical Behavior Therapy in College Counseling Centers: Current Literature and Implications for Practice

ERIC Educational Resources Information Center

Chugani, Carla D.

2015-01-01

This article examines the topic of Dialectical Behavior Therapy (DBT) applied in college counseling centers. Trends in mental health issues on college campuses are briefly reviewed in support of the increased need for evidence-based treatment of severe mental health issues. The article next presents an overview of the standard DBT model and…

Refractory Immune Thrombocytopenic Purpura and Cytomegalovirus Infection: A Call for a Change in the Current Guidelines.

PubMed

Shimanovsky, Alexei; Patel, Devbala; Wasser, Jeffrey

2016-01-01

Immune thrombocytopenic purpura (ITP) is characterized by a decreased platelet count caused by excess destruction of platelets and inadequate platelet production. In many cases, the etiology is not known, but the viral illness is thought to play a role in the development of some cases of ITP. The current (2011) American Society of Hematology ITP guidelines recommend initial diagnostic studies to include testing for HIV and Hepatitis C. The guidelines suggest that initial treatment consist of observation, therapy with corticosteroids, IVIG or anti D. Most cases respond to the standard therapy such that the steroids may be tapered and the platelet counts remain at a hemostatically safe level. Some patients with ITP are dependent on long-term steroid maintenance, and the thrombocytopenia persists with the tapering of the steroids. Recent case reports demonstrate that ITP related to cytomegalovirus (CMV) can persist in spite of standard therapy and that antiviral therapy may be indicated. Herein we report a case of a 26-year-old female with persistent ITP that resolved after the delivery of a CMV-infected infant and placenta. Furthermore, we review the current literature on CMV-associated ITP and propose that the current ITP guidelines be amended to include assessment for CMV, even in the absence of signs and symptoms, as part of the work-up for severe and refractory ITP, especially prior to undergoing an invasive procedure such as splenectomy.

Refractory Immune Thrombocytopenic Purpura and Cytomegalovirus Infection: A Call for a Change in the Current Guidelines

PubMed Central

Shimanovsky, Alexei; Patel, Devbala; Wasser, Jeffrey

2016-01-01

Immune thrombocytopenic purpura (ITP) is characterized by a decreased platelet count caused by excess destruction of platelets and inadequate platelet production. In many cases, the etiology is not known, but the viral illness is thought to play a role in the development of some cases of ITP. The current (2011) American Society of Hematology ITP guidelines recommend initial diagnostic studies to include testing for HIV and Hepatitis C. The guidelines suggest that initial treatment consist of observation, therapy with corticosteroids, IVIG or anti D. Most cases respond to the standard therapy such that the steroids may be tapered and the platelet counts remain at a hemostatically safe level. Some patients with ITP are dependent on long-term steroid maintenance, and the thrombocytopenia persists with the tapering of the steroids. Recent case reports demonstrate that ITP related to cytomegalovirus (CMV) can persist in spite of standard therapy and that antiviral therapy may be indicated. Herein we report a case of a 26-year-old female with persistent ITP that resolved after the delivery of a CMV-infected infant and placenta. Furthermore, we review the current literature on CMV-associated ITP and propose that the current ITP guidelines be amended to include assessment for CMV, even in the absence of signs and symptoms, as part of the work-up for severe and refractory ITP, especially prior to undergoing an invasive procedure such as splenectomy. PMID:26740871

TU-G-213-00: The International Electrotechnical Commission (IEC): What Is It and Why Should Medical Physicists Care?

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

NONE

The International Electrotechnical Commission (IEC) writes standards that manufacturers of electrical equipment must comply with. Medical electrical equipment, such as medical imaging, radiation therapy, and radiation dosimetry devices, fall under Technical Committee 62. Of particular interest to medical physicists are the standards developed within Subcommittees (SC) 62B, which addresses diagnostic radiological imaging equipment, and 62C, which addresses equipment for radiation therapy, nuclear medicine and dosimetry. For example, a Working Group of SC 62B is responsible for safety and quality assurance standards for CT scanners and a Working Group of SC 62C is responsible for standards that set requirements for dosimetricmore » safety and accuracy of linacs and proton accelerators. IEC standards thus have an impact on every aspect of a medical physicist’s job, including equipment testing, shielding design, room layout, and workflow. Consequently, it is imperative that US medical physicists know about existing standards, as well as have input on those under development or undergoing revision. The structure of the IEC and current standards development work will be described in detail. The presentation will explain how US medical physicists can learn about IEC standards and contribute to their development. Learning Objectives: Learn about the structure of the IEC and the influence that IEC standards have on the design of equipment for radiology and radiation therapy. Learn about the mechanisms by which the US participates in the development and revision of standards. Understand the specific requirements of several standards having direct relevance to diagnostic and radiation therapy physicists.« less

TU-G-213-01: IEC and US Committee Activities and Organizational Structure

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

Ibbott, G.

2015-06-15

The International Electrotechnical Commission (IEC) writes standards that manufacturers of electrical equipment must comply with. Medical electrical equipment, such as medical imaging, radiation therapy, and radiation dosimetry devices, fall under Technical Committee 62. Of particular interest to medical physicists are the standards developed within Subcommittees (SC) 62B, which addresses diagnostic radiological imaging equipment, and 62C, which addresses equipment for radiation therapy, nuclear medicine and dosimetry. For example, a Working Group of SC 62B is responsible for safety and quality assurance standards for CT scanners and a Working Group of SC 62C is responsible for standards that set requirements for dosimetricmore » safety and accuracy of linacs and proton accelerators. IEC standards thus have an impact on every aspect of a medical physicist’s job, including equipment testing, shielding design, room layout, and workflow. Consequently, it is imperative that US medical physicists know about existing standards, as well as have input on those under development or undergoing revision. The structure of the IEC and current standards development work will be described in detail. The presentation will explain how US medical physicists can learn about IEC standards and contribute to their development. Learning Objectives: Learn about the structure of the IEC and the influence that IEC standards have on the design of equipment for radiology and radiation therapy. Learn about the mechanisms by which the US participates in the development and revision of standards. Understand the specific requirements of several standards having direct relevance to diagnostic and radiation therapy physicists.« less

TU-G-213-03: IEC Subcommittee 62C (Equipment for Radiotherapy, Nuclear Medicine and Radiation Dosimetry): Recent and Active Projects

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

Culberson, W.

The International Electrotechnical Commission (IEC) writes standards that manufacturers of electrical equipment must comply with. Medical electrical equipment, such as medical imaging, radiation therapy, and radiation dosimetry devices, fall under Technical Committee 62. Of particular interest to medical physicists are the standards developed within Subcommittees (SC) 62B, which addresses diagnostic radiological imaging equipment, and 62C, which addresses equipment for radiation therapy, nuclear medicine and dosimetry. For example, a Working Group of SC 62B is responsible for safety and quality assurance standards for CT scanners and a Working Group of SC 62C is responsible for standards that set requirements for dosimetricmore » safety and accuracy of linacs and proton accelerators. IEC standards thus have an impact on every aspect of a medical physicist’s job, including equipment testing, shielding design, room layout, and workflow. Consequently, it is imperative that US medical physicists know about existing standards, as well as have input on those under development or undergoing revision. The structure of the IEC and current standards development work will be described in detail. The presentation will explain how US medical physicists can learn about IEC standards and contribute to their development. Learning Objectives: Learn about the structure of the IEC and the influence that IEC standards have on the design of equipment for radiology and radiation therapy. Learn about the mechanisms by which the US participates in the development and revision of standards. Understand the specific requirements of several standards having direct relevance to diagnostic and radiation therapy physicists.« less

Antibiotic treatment for Helicobacter pylori: Is the end coming?

PubMed Central

Kim, Su Young; Choi, Duck Joo; Chung, Jun-Won

2015-01-01

Infection with the Gram-negative pathogen Helicobacter pylori (H. pylori) has been associated with gastro-duodenal disease and the importance of H. pylori eradication is underscored by its designation as a group I carcinogen. The standard triple therapy consists of a proton pump inhibitor, amoxicillin and clarithromycin, although many other regimens are used, including quadruple, sequential and concomitant therapy regimens supplemented with metronidazole, clarithromycin and levofloxacin. Despite these efforts, current therapeutic regimens lack efficacy in eradication due to antibiotic resistance, drug compliance and antibiotic degradation by the acidic stomach environment. Antibiotic resistance to clarithromycin and metronidazole is particularly problematic and several approaches have been proposed to overcome this issue, such as complementary probiotic therapy with Lactobacillus. Other studies have identified novel molecules with an anti-H. pylori effect, as well as tailored therapy and nanotechnology as viable alternative eradication strategies. This review discusses current antibiotic therapy for H. pylori infections, limitations of this type of therapy and predicts the availability of newly developed therapies for H. pylori eradication. PMID:26558152

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.

[Music therapy and depression].

PubMed

Van Assche, E; De Backer, J; Vermote, R

2015-01-01

Music therapy is a predominantly non-verbal psychotherapy based on music improvisation, embedded in a therapeutic relationship. This is the reason why music therapy is also used to treat depression. To examine the efficacy of music therapy and to report on the results of recent research into the value of music therapy as a treatment for depression. We reviewed the literature on recent research into music therapy and depression, reporting on the methods used and the results achieved, and we assessed the current position of music therapy for depression in the context of evidence-based scientific research. A wide variety of research methods was used to investigate the effects of using music therapy as a psychotherapy. Most studies focused usually on the added value that music therapy brings to the standard form of psychiatric treatment, when administered with or without psychopharmacological support. Music therapy produced particularly significant and favourable results when used to treat patients with depression. Current research into music therapy and depression points to a significant and persistent reduction in patients' symptoms and to improvements in their quality of life. However, further research is needed with regard to the best methods of illustrating the effects of music therapy.

Bioreactor Engineering of Stem Cell Environments

PubMed Central

Tandon, Nina; Marolt, Darja; Cimetta, Elisa; Vunjak-Novakovic, Gordana

2013-01-01

Stem cells hold promise to revolutionize modern medicine by development of new therapies, disease models and drug screening systems. Standard cell culture systems have limited biological relevance because they do not recapitulate the complex 3-dimensional interactions and biophysical cues that characterize the in vivo environment. In this review, we discuss the current advances in engineering stem cell environments using novel biomaterials and bioreactor technologies. We also reflect on the challenges the field is currently facing with regard to translation of stem cell based therapies into the clinic. PMID:23531529

Practice patterns of image guided particle therapy in Europe: A 2016 survey of the European Particle Therapy Network (EPTN).

PubMed

Bolsi, Alessandra; Peroni, Marta; Amelio, Dante; Dasu, Alexandru; Stock, Markus; Toma-Dasu, Iuliana; Nyström, Petra Witt; Hoffmann, Aswin

2018-03-28

Image guidance is critical in achieving accurate and precise radiation delivery in particle therapy, even more than in photon therapy. However, equipment, quality assurance procedures and clinical workflows for image-guided particle therapy (IGPT) may vary substantially between centres due to a lack of standardization. A survey was conducted to evaluate the current practice of IGPT in European particle therapy centres. In 2016, a questionnaire was distributed among 19 particle therapy centres in 12 European countries. The questionnaire consisted of 30 open and 37 closed questions related to image guidance in the general clinical workflow, for moving targets, current research activities and future perspectives of IGPT. All centres completed the questionnaire. The IGPT methods used by the 10 treating centres varied substantially. The 9 non-treating centres were in the process to introduce IGPT. Most centres have developed their own IGPT strategies, being tightly connected to their specific technical implementation and dose delivery methods. Insight into the current clinical practice of IGPT in European particle therapy centres was obtained. A variety in IGPT practices and procedures was confirmed, which underlines the need for harmonisation of practice parameters and consensus guidelines. Copyright © 2018 Elsevier B.V. All rights reserved.

Effectiveness of Group Cognitive-Behavioral Therapy on Symptoms of Premenstrual Syndrome (PMS) ‎.

PubMed

Maddineshat, Maryam; Keyvanloo, Sodabe; Lashkardoost, Hossein; Arki, Mina; Tabatabaeichehr, Mahbubeh

2016-01-01

Standards of care and treatment of premenstrual syndrome (PMS) vary. Non-drug ‎psychosocial intervention therapy is recommended for women with any kind of ‎discomfort or distress caused by PMS. The current study examined the effectiveness of ‎group cognitive-behavioral therapy on the symptoms of PMS at a girls' dormitory of ‎North Khorasan University of Medical Sciences. In this quasi-experimental study, 32 female students with PMS who were majoring in ‎nursing and midwifery and residing in the dormitory were selected using the ‎convenience sampling method and were assigned to experimental and control groups. ‎The Standardized Premenstrual Symptoms Screening Tool was used as the research ‎tool. Eight sessions of cognitive-behavioral group therapy were held for the students Results: There was a significant difference in psychological symptoms before and after ‎cognitive-behavioral therapy (p=0.012). Furthermore, cognitive-behavioral therapy was ‎effective on social interferences caused by PMS symptoms (p=0.012).‎ Group cognitive-behavioral therapy effectively alleviates PMS symptoms in female ‎college students.‎.

Cervical dystonia: effectiveness of a standardized physical therapy program; study design and protocol of a single blind randomized controlled trial

PubMed Central

2013-01-01

Background Cervical dystonia is characterized by involuntary muscle contractions of the neck and abnormal head positions that affect daily life activities and social life of patients. Patients are usually treated with botulinum toxin injections into affected neck muscles to relief pain and improve control of head postures. In addition, many patients are referred for physical therapy to improve their ability to perform activities of daily living. A recent review on allied health interventions in cervical dystonia showed a lack of randomized controlled intervention studies regarding the effectiveness of physical therapy interventions. Methods/design The (cost-) effectiveness of a standardized physical therapy program compared to regular physical therapy, both as add-on treatment to botulinum toxin injections will be determined in a multi-centre, single blinded randomized controlled trial with 100 cervical dystonia patients. Primary outcomes are disability in daily functioning assessed with the disability subscale of the Toronto Western Spasmodic Torticollis Rating Scale. Secondary outcomes are pain, severity of dystonia, active range of motion of the head, quality of life, anxiety and depression. Data will be collected at baseline, after six months and one year by an independent blind assessor just prior to botulinum toxin injections. For the cost effectiveness, an additional economic evaluation will be performed with the costs per quality adjusted life-year as primary outcome parameter. Discussion Our study will provide new evidence regarding the (cost-) effectiveness of a standardized, tailored physical therapy program for patients with cervical dystonia. It is widely felt that allied health interventions, including physical therapy, may offer a valuable supplement to the current therapeutic options. A positive outcome will lead to a greater use of the standardized physical therapy program. For the Dutch situation a positive outcome implies that the standardized physical therapy program forms the basis for a national treatment guideline for cervical dystonia. Trial registration Number Dutch Trial registration (Nederlands Trial Register): NTR3437 PMID:23855591

Cervical dystonia: effectiveness of a standardized physical therapy program; study design and protocol of a single blind randomized controlled trial.

PubMed

van den Dool, Joost; Visser, Bart; Koelman, J Hans T M; Engelbert, Raoul H H; Tijssen, Marina A J

2013-07-15

Cervical dystonia is characterized by involuntary muscle contractions of the neck and abnormal head positions that affect daily life activities and social life of patients. Patients are usually treated with botulinum toxin injections into affected neck muscles to relief pain and improve control of head postures. In addition, many patients are referred for physical therapy to improve their ability to perform activities of daily living. A recent review on allied health interventions in cervical dystonia showed a lack of randomized controlled intervention studies regarding the effectiveness of physical therapy interventions. The (cost-) effectiveness of a standardized physical therapy program compared to regular physical therapy, both as add-on treatment to botulinum toxin injections will be determined in a multi-centre, single blinded randomized controlled trial with 100 cervical dystonia patients. Primary outcomes are disability in daily functioning assessed with the disability subscale of the Toronto Western Spasmodic Torticollis Rating Scale. Secondary outcomes are pain, severity of dystonia, active range of motion of the head, quality of life, anxiety and depression. Data will be collected at baseline, after six months and one year by an independent blind assessor just prior to botulinum toxin injections. For the cost effectiveness, an additional economic evaluation will be performed with the costs per quality adjusted life-year as primary outcome parameter. Our study will provide new evidence regarding the (cost-) effectiveness of a standardized, tailored physical therapy program for patients with cervical dystonia. It is widely felt that allied health interventions, including physical therapy, may offer a valuable supplement to the current therapeutic options. A positive outcome will lead to a greater use of the standardized physical therapy program. For the Dutch situation a positive outcome implies that the standardized physical therapy program forms the basis for a national treatment guideline for cervical dystonia. Number Dutch Trial registration (Nederlands Trial Register): NTR3437.

Budesonide as first-line therapy for non-cirrhotic autoimmune hepatitis in children: a decision analysis.

PubMed

Mohammad, Saeed

2016-01-01

Therapy for autoimmune hepatitis has been prednisone based for decades; however, budesonide may be equally effective with fewer side effects. Our aim was to evaluate quality-adjusted life years and health care costs of three different treatment regimens. Treatment using prednisone, budesonide or a combination of both over a three-year period in newly diagnosed children with type I autoimmune hepatitis were simulated with a Markov model. Transition probabilities were calculated over consecutive three-month period. Costs were determined from a hospital database and health utilities were estimated from the literature. A Monte Carlo probabilistic sensitivity analysis was used to simulate the outcomes of 5000 patients in each treatment arm. Compared to standard therapy, budesonide leads to a gain of 0.09 quality-adjusted life years, costing $17,722 per QALY over a three-year period. Standard therapy led to significantly lower QALY's compared to other strategies (p < 0.001). Health utilities of patients in remission in each treatment group had the greatest impact on the model. Budesonide remained the treatment of choice if the probability of inducing remission was 55% or greater. Budesonide therapy in non-cirrhotic, treatment naïve patients with type I autoimmune hepatitis yielded greater QALY's compared to the current standard therapy with an acceptable increase in costs.

MO-A-BRD-00: Current Trends in Y90-Microsphere Therapy: Delivery and Dosimetry

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

NONE

2015-06-15

Yttrium-90 (Y90) microsphere therapy, a form of radiation therapy, is an increasingly popular option for care of patients with liver metastases or unresectable hepatocellular carcinoma. The therapy directly delivers Y90 microspheres via the hepatic artery to disease sites. Following delivery, a vast majority of microspheres preferentially lodge in the capillary vessels due to their embolic size and targeted trans-arterial delivery – depositing up to 90% of its energy in the first 5 mm of tissue. There have been a number of advances in tomographic imaging within both interventional radiology and nuclear medicine that has advanced therapy planning techniques. Quantitative imagingmore » of Y90 microsphere distribution post-therapy has also seen innovations that have led to improvements in tumor dosimetry and characterization of tumor response. A review of current trends and recent innovation in Y90 microsphere therapies will be presented. Learning Objectives: To present the imaging requirements for Y90 microsphere therapy planning To explain the standard dosimetry models used in Y90 microsphere therapy planning To report on advances in imaging for therapy planning and posttherapy assessment of tumor dosimetry and response.« less

Management of intracerebral pressure in the neurosciences critical care unit.

PubMed

Marshall, Scott A; Kalanuria, Atul; Markandaya, Manjunath; Nyquist, Paul A

2013-07-01

Management of intracranial pressure in neurocritical care remains a potentially valuable target for improvements in therapy and patient outcomes. Surrogate markers of increased intracranial pressure, invasive monitors, and standard therapy, as well as promising new approaches to improve cerebral compliance are discussed, and a current review of the literature addressing this metric in neuroscience critical care is provided. Published by Elsevier Inc.

Group art therapy as an adjunctive treatment for people with schizophrenia: multicentre pragmatic randomised trial

PubMed Central

Killaspy, Helen; Barnes, Thomas R E; Barrett, Barbara; Byford, Sarah; Clayton, Katie; Dinsmore, John; Floyd, Siobhan; Hoadley, Angela; Johnson, Tony; Kalaitzaki, Eleftheria; King, Michael; Leurent, Baptiste; Maratos, Anna; O’Neill, Francis A; Osborn, David P; Patterson, Sue; Soteriou, Tony; Tyrer, Peter; Waller, Diane

2012-01-01

Objectives To evaluate the clinical effectiveness of group art therapy for people with schizophrenia and to test whether any benefits exceed those of an active control treatment. Design Three arm, rater blinded, pragmatic, randomised controlled trial. Setting Secondary care services across 15 sites in the United Kingdom. Participants 417 people aged 18 or over, who had a diagnosis of schizophrenia and provided written informed consent to take part in the study. Interventions Participants, stratified by site, were randomised to 12 months of weekly group art therapy plus standard care, 12 months of weekly activity groups plus standard care, or standard care alone. Art therapy and activity groups had up to eight members and lasted for 90 minutes. In art therapy, members were given access to a range of art materials and encouraged to use these to express themselves freely. Members of activity groups were offered various activities that did not involve use of art or craft materials and were encouraged to collectively select those they wanted to pursue. Main outcome measures The primary outcomes were global functioning, measured using the global assessment of functioning scale, and mental health symptoms, measured using the positive and negative syndrome scale, 24 months after randomisation. Main secondary outcomes were levels of group attendance, social functioning, and satisfaction with care at 12 and 24 months. Results 417 participants were assigned to either art therapy (n=140), activity groups (n=140), or standard care alone (n=137). Primary outcomes between the three study arms did not differ. The adjusted mean difference between art therapy and standard care at 24 months on the global assessment of functioning scale was −0.9 (95% confidence interval −3.8 to 2.1), and on the positive and negative syndrome scale was 0.7 (−3.1 to 4.6). Secondary outcomes did not differ between those referred to art therapy or those referred to standard care at 12 or 24 months. Conclusions Referring people with established schizophrenia to group art therapy as delivered in this trial did not improve global functioning, mental health, or other health related outcomes. Trial registration Current Controlled Trials ISRCTN46150447. PMID:22374932

Esophageal cancer: the latest on chemoprevention and state of the art therapies

PubMed Central

Le Bras, Gregoire F.; Farooq, Muhammad H.; Falk, Gary W.; Andl, Claudia D

2016-01-01

Esophageal cancer is currently the 8th most common cancer worldwide and the 6th leading cause of cancer-related mortality. Despite remarkable advances, the mortality for those suffering from esophageal cancer remains high, with 5-year survival rates of less than 20%. In part, because most patients present with late-stage disease, long-term survival even after resection and therapy is disappointingly low. As we will discuss in this review, multiple characteristics specific to the disease stage and patient must be considered when choosing a treatment plan. This article will summarize current standard therapies, potential application of chemoprevention drugs and the promise and partial failure of personalized medicine, as well as novel treatments addressing this disease. PMID:27565381

Effect of bronchoalveolar lavage-directed therapy on Pseudomonas aeruginosa infection and structural lung injury in children with cystic fibrosis: a randomized trial.

PubMed

Wainwright, Claire E; Vidmar, Suzanna; Armstrong, David S; Byrnes, Catherine A; Carlin, John B; Cheney, Joyce; Cooper, Peter J; Grimwood, Keith; Moodie, Marj; Robertson, Colin F; Tiddens, Harm A

2011-07-13

Early pulmonary infection in children with cystic fibrosis leads to increased morbidity and mortality. Despite wide use of oropharyngeal cultures to identify pulmonary infection, concerns remain over their diagnostic accuracy. While bronchoalveolar lavage (BAL) is an alternative diagnostic tool, evidence for its clinical benefit is lacking. To determine if BAL-directed therapy for pulmonary exacerbations during the first 5 years of life provides better outcomes than current standard practice relying on clinical features and oropharyngeal cultures. The Australasian Cystic Fibrosis Bronchoalveolar Lavage (ACFBAL) randomized controlled trial, recruiting infants diagnosed with cystic fibrosis through newborn screening programs in 8 Australasian cystic fibrosis centers. Recruitment occurred between June 1, 1999, and April 30, 2005, with the study ending on December 31, 2009. BAL-directed (n = 84) or standard (n = 86) therapy until age 5 years. The BAL-directed therapy group underwent BAL before age 6 months when well, when hospitalized for pulmonary exacerbations, if Pseudomonas aeruginosa was detected in oropharyngeal specimens, and after P. aeruginosa eradication therapy. Treatment was prescribed according to BAL or oropharyngeal culture results. Primary outcomes at age 5 years were prevalence of P. aeruginosa on BAL cultures and total cystic fibrosis computed tomography (CF-CT) score (as a percentage of the maximum score) on high-resolution chest CT scan. Of 267 infants diagnosed with cystic fibrosis following newborn screening, 170 were enrolled and randomized, and 157 completed the study. At age 5 years, 8 of 79 children (10%) in the BAL-directed therapy group and 9 of 76 (12%) in the standard therapy group had P. aeruginosa in final BAL cultures (risk difference, -1.7% [95% confidence interval, -11.6% to 8.1%]; P = .73). Mean total CF-CT scores for the BAL-directed therapy and standard therapy groups were 3.0% and 2.8%, respectively (mean difference, 0.19% [95% confidence interval, -0.94% to 1.33%]; P = .74). Among infants diagnosed with cystic fibrosis, BAL-directed therapy did not result in a lower prevalence of P. aeruginosa infection or lower total CF-CT score when compared with standard therapy at age 5 years. anzctr.org.au Identifier: ACTRN12605000665639.

'Muscle-sparing' statins: preclinical profiles and future clinical use.

PubMed

Pfefferkorn, Jeffrey A

2009-03-01

Coronary heart disease (CHD) is a leading cause of death in the US, and hypercholesterolemia is a key risk factor for this disease. The current standard of care for treating hypercholesterolemia is the use of HMG-CoA reductase inhibitors, also known as statins, which block the rate-limiting step of cholesterol biosynthesis. In widespread clinical use, statins have proven safe and effective for both primary prevention of CHD and secondary prevention of coronary events. Results from several recent clinical trials have demonstrated that increasingly aggressive cholesterol-lowering therapy might offer additional protection against CHD compared with less aggressive treatment standards. While higher doses of current statin therapies are capable of achieving these more aggressive treatment goals, in certain cases statin-induced myalgia, the muscle pain or weakness that sometimes accompanies high-dose statin therapy, limits patient compliance with a treatment regimen. To address this limitation, efforts have been undertaken to develop highly hepatoselective statins that are capable of delivering best-in-class efficacy with minimized risk of dose-limiting myalgia. In this review, the preclinical and early clinical data for these next generation statins are discussed.

Bioreactor engineering of stem cell environments.

PubMed

Tandon, Nina; Marolt, Darja; Cimetta, Elisa; Vunjak-Novakovic, Gordana

2013-11-15

Stem cells hold promise to revolutionize modern medicine by the development of new therapies, disease models and drug screening systems. Standard cell culture systems have limited biological relevance because they do not recapitulate the complex 3-dimensional interactions and biophysical cues that characterize the in vivo environment. In this review, we discuss the current advances in engineering stem cell environments using novel biomaterials and bioreactor technologies. We also reflect on the challenges the field is currently facing with regard to the translation of stem cell based therapies into the clinic. Copyright © 2013 Elsevier Inc. All rights reserved.

Endometriosis: Survey of Current Diagnostic and Therapeutic Options and Latest Research Work

PubMed Central

Juhasz-Böss, I.; Laschke, M. W.; Müller, F.; Rosenbaum, P.; Baum, S.; Solomayer, E. F.; Ulrich, U.

2014-01-01

Endometriosis is one of the most frequent benign diseases in women of child-bearing age. The main symptoms are chronic upper abdominal pain and infertility. However, the aetiology and pathogenesis of endometriosis are as yet insufficiently clarified. Thus, therapy is mainly symptomatic with laparoscopic surgery being the gold standard. The aim of drug therapy is to achieve a hypo-oestrogenic condition. In cases of severe endometriosis and a desire to have children there is often an indication for assisted reproduction. The present article illustrates almost all current aspects on the diagnosis of and therapy of endometriosis. From the clinical viewpoint, emphasis is placed on the rare cases of deeply infiltrating endometriosis that are, however, accompanied with a high morbidity. Current therapeutic options in cases of infertility are also presented in more detail. Furthermore, special attention is paid to the latest research results from both clinical and basic research fields in order to demonstrate our current knowledge on the pathogenesis and, where possible, potentially related therapeutic options. PMID:25221341

The future of high-grade glioma: Where we are and where are we going

PubMed Central

Rhun, Emilie Le; Taillibert, Sophie; Chamberlain, Marc C.

2015-01-01

High-grade glioma (HGG) are optimally treated with maximum safe surgery, followed by radiotherapy (RT) and/or systemic chemotherapy (CT). Recently, the treatment of newly diagnosed anaplastic glioma (AG) has changed, particularly in patients with 1p19q codeleted tumors. Results of trials currenlty ongoing are likely to determine the best standard of care for patients with noncodeleted AG tumors. Trials in AG illustrate the importance of molecular characterization, which are germane to both prognosis and treatment. In contrast, efforts to improve the current standard of care of newly diagnosed glioblastoma (GB) with, for example, the addition of bevacizumab (BEV), have been largely disappointing and furthermore molecular characterization has not changed therapy except in elderly patients. Novel approaches, such as vaccine-based immunotherapy, for newly diagnosed GB are currently being pursued in multiple clinical trials. Recurrent disease, an event inevitable in nearly all patients with HGG, continues to be a challenge. Both recurrent GB and AG are managed in similar manner and when feasible re-resection is often suggested notwithstanding limited data to suggest benefit from repeat surgery. Occassional patients may be candidates for re-irradiation but again there is a paucity of data to commend this therapy and only a minority of selected patients are eligible for this approach. Consequently systemic therapy continues to be the most often utilized treatment in recurrent HGG. Choice of therapy, however, varies and revolves around re-challenge with temozolomide (TMZ), use of a nitrosourea (most often lomustine; CCNU) or BEV, the most frequently used angiogenic inhibitor. Nevertheless, no clear standard recommendation regarding the prefered agent or combination of agents is avaliable. Prognosis after progression of a HGG remains poor, with an unmet need to improve therapy. PMID:25722939

The future of high-grade glioma: Where we are and where are we going.

PubMed

Le Rhun, Emilie; Rhun, Emilie Le; Taillibert, Sophie; Chamberlain, Marc C

2015-01-01

High-grade glioma (HGG) are optimally treated with maximum safe surgery, followed by radiotherapy (RT) and/or systemic chemotherapy (CT). Recently, the treatment of newly diagnosed anaplastic glioma (AG) has changed, particularly in patients with 1p19q codeleted tumors. Results of trials currenlty ongoing are likely to determine the best standard of care for patients with noncodeleted AG tumors. Trials in AG illustrate the importance of molecular characterization, which are germane to both prognosis and treatment. In contrast, efforts to improve the current standard of care of newly diagnosed glioblastoma (GB) with, for example, the addition of bevacizumab (BEV), have been largely disappointing and furthermore molecular characterization has not changed therapy except in elderly patients. Novel approaches, such as vaccine-based immunotherapy, for newly diagnosed GB are currently being pursued in multiple clinical trials. Recurrent disease, an event inevitable in nearly all patients with HGG, continues to be a challenge. Both recurrent GB and AG are managed in similar manner and when feasible re-resection is often suggested notwithstanding limited data to suggest benefit from repeat surgery. Occassional patients may be candidates for re-irradiation but again there is a paucity of data to commend this therapy and only a minority of selected patients are eligible for this approach. Consequently systemic therapy continues to be the most often utilized treatment in recurrent HGG. Choice of therapy, however, varies and revolves around re-challenge with temozolomide (TMZ), use of a nitrosourea (most often lomustine; CCNU) or BEV, the most frequently used angiogenic inhibitor. Nevertheless, no clear standard recommendation regarding the prefered agent or combination of agents is avaliable. Prognosis after progression of a HGG remains poor, with an unmet need to improve therapy.

The Stem-Cell Market for the Treatment of Knee Osteoarthritis: A Patient Perspective.

PubMed

Piuzzi, Nicolas S; Ng, Mitchell; Chughtai, Morad; Khlopas, Anton; Ng, Kenneth; Mont, Michael A; Muschler, George F

2018-07-01

The use of stem-cell therapies for the treatment of various musculoskeletal conditions, especially knee osteoarthritis (OA), is rapidly expanding, despite only low-level evidence to support its use. Centers offering these therapies are often marketing and charging patients out-of-pocket costs for such services. Therefore, the purpose of this study was to determine the current marketed: (1) prices and (2) clinical efficacy of stem-cell therapies for knee OA. This was a prospective cross-sectional study which queried 317 U.S. centers that offered direct-to-consumer stem-cell therapies for musculoskeletal conditions. A total of 273 of 317 centers were successfully contacted via phone or e-mail, using a simulated 57-year-old male patient with knee OA. Scripted questions were asked by the simulated patient to determine the marketed prices and clinical efficacy. Centers generally reported the proportion of patients who had "good results" or "symptomatic improvement." The mean price of a unilateral (same-day) stem-cell knee injection was $5,156 with a standard deviation of $2,446 (95% confidence interval [CI]: $4,550-5,762, n  = 65). The mean proportion of claimed clinical efficacy was 82% with a standard deviation of 9.6% (95% CI: 79.0-85.5%, n  = 36). Most American stem-cell centers offer therapies for knee OA. The cost of these therapies averages about $5,000 per injection, and centers claim that 80% of the patients had "good results" or "symptomatic improvement," denoting a gap between what is documented in the published literature and the marketing claims. These findings offer both patients and physicians insight into the current stem-cell market for knee OA. We hope that with this information, providers can more optimally make patients aware of discrepancies between what is being marketed versus the current evidence-based landscape of these therapies for knee OA. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

An assessment of the current treatment landscape for rheumatology patients in Qatar: Recognising unmet needs and moving towards solutions.

PubMed

Emadi, Samar Al; Hammoudeh, Mohammed; Mounir, Mohamed; Mueller, Ruediger B; Wells, Alvin F; Sarakbi, Housam Aldeen

2017-04-01

Objective This study assessed the mode of application (oral, intravenous or subcutaneous (SC)) currently employed in the treatment of rheumatoid arthritis (RA) in patients from Qatar in comparison with patients' individual preferences for the mode of application of their treatment. Methods This study included 294 RA patients visiting three clinics at the main referral hospital in Qatar who were interviewed using a standard questionnaire to determine their preference of mode of application for their disease-modifying antirheumatic drug (DMARD) treatment in relation to their currently employed mode of application. Results The majority of patients were female (76%), and 93% of male patients and 61% of female patients in the study clinics were of a nationality other than Qatari. The highest patient preference recorded was for an oral therapy (69%), compared with injection (23%) and intravenous (8%) therapy. In total, 85% of patients expressed a preference to remain on oral therapy compared with 63% and 58% of intravenous and SC injection patients indicating a preference to remain on their current method of administration. Conclusions This high preference for oral therapies highlights the considerable need for incorporation of new oral targeted synthetic DMARD therapies into clinical practice within the region.

An assessment of the current treatment landscape for rheumatology patients in Qatar: Recognising unmet needs and moving towards solutions

PubMed Central

Hammoudeh, Mohammed; Mounir, Mohamed; Mueller, Ruediger B.; Wells, Alvin F.; Sarakbi, Housam Aldeen

2017-01-01

Objective This study assessed the mode of application (oral, intravenous or subcutaneous (SC)) currently employed in the treatment of rheumatoid arthritis (RA) in patients from Qatar in comparison with patients’ individual preferences for the mode of application of their treatment. Methods This study included 294 RA patients visiting three clinics at the main referral hospital in Qatar who were interviewed using a standard questionnaire to determine their preference of mode of application for their disease-modifying antirheumatic drug (DMARD) treatment in relation to their currently employed mode of application. Results The majority of patients were female (76%), and 93% of male patients and 61% of female patients in the study clinics were of a nationality other than Qatari. The highest patient preference recorded was for an oral therapy (69%), compared with injection (23%) and intravenous (8%) therapy. In total, 85% of patients expressed a preference to remain on oral therapy compared with 63% and 58% of intravenous and SC injection patients indicating a preference to remain on their current method of administration. Conclusions This high preference for oral therapies highlights the considerable need for incorporation of new oral targeted synthetic DMARD therapies into clinical practice within the region. PMID:28415924

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.

Efficacy vs. effectiveness research in psychotherapy: implications for clinical hypnosis.

PubMed

Amundson, Jon K; Alladin, Assen; Eamon, Gill

2003-07-01

Empirically supported therapy (EST) has become a major focus and trend for mental health practice. When hypnosis is involved, this may mean satisfying a standard that is entirely too narrow in its emphasis. In this article "efficacy"-based research in clinical practice is contrasted with "effectiveness" -focused research, and they are discussed from the perspective of hypnosis. When clinicians can consider trans-theoretical factors as well as those that are treatment-enhancing, possibilities for improved treatment outcome increase. The "effectiveness" perspective also serves as a counter point for hypnosis in contrast with the dubious efficacy-based gold standard currently proposed for therapy in general, and hypnosis in particular.

Use of polyclonal/monoclonal antibody therapies in transplantation.

PubMed

Yeung, Melissa Y; Gabardi, Steven; Sayegh, Mohamed H

2017-03-01

For over thirty years, antibody (mAb)-based therapies have been a standard component of transplant immunosuppression, and yet much remains to be learned in order for us to truly harness their therapeutic capabilities. Current mAbs used in transplant directly target and destroy graft-destructive immune cells, interrupt cytokine and costimulation-dependent T and B cell activation, and prevent down-stream complement activation. Areas covered: This review summarizes our current approaches to using antibody-based therapies to prevent and treat allograft rejection. It also provides examples of promising novel mAb therapies, and discusses the potential for future mAb development in transplantation. Expert opinion: The broad capability of antibodies, in parallel with our growing ability to synthetically modulate them, offers exciting opportunities to develop better biologic therapeutics. In order to do so, we must further our understanding about the basic biology underlying allograft rejection, and gain better appreciation of how characteristics of therapeutic antibodies affect their efficacy.

[Biotechnological therapies for the treatment of back pain: alternatives to corticosteroids].

PubMed

Moser, C; Thiel, H-J; Grönemeyer, D

2013-12-01

In recent years, it is increasingly clear that back pain is not only caused by biomechanical problems. Currently, biologically-based local therapy concepts for the treatment of affected spinal regions as an alternative to the standard treatment with steroids are in development or in early stages of clinical application. The common features of these new therapies are to intervene in the regulation of homeostasis at various key points at the affected region and specifically to suppress or block catabolic influences as well as to provide with anti-inflammatory substances and growth factors. These include on one hand the genetically produced Biologicals such as TNF-α inhibitors and cytokine antagonists and on the other hand therapies with autologous blood preparations (Autologous Conditioned Serum [ACS], and Platelet Rich Plasma formulations [PRP]). This article presents the individual methods, gives an overview of developments and results of various studies and discusses current recommendations.

A Conceptual Framework for Addressing Residual Atherosclerotic Cardiovascular Disease Risk in the Era of Precision Medicine.

PubMed

Patel, Kershaw V; Pandey, Ambarish; de Lemos, James A

2018-04-11

Until recently, therapies to mitigate atherosclerotic cardiovascular disease (ASCVD) risk have been limited to lifestyle interventions, blood pressure lowering medications, high intensity statin therapy, antiplatelet agents, and in select patients, coronary artery revascularization. Despite administration of these evidence-based therapies, substantial residual risk for cardiovascular events persists, particularly among individuals with known ASCVD. Moreover, the current guideline-based approach does not adequately account for patient-specific, causal pathways that lead to ASCVD progression and complications. In the past few years, multiple new pharmacological agents, targeting conceptually distinct pathophysiological targets, have been shown in large and well-conducted clinical trials to lower cardiovascular risk among patients with established ASCVD receiving guideline directed medical care. These evidenced-based therapies reduce event rates, and in some cases all-cause and cardiovascular mortality; these benefits confirm important new disease targets and challenge the adequacy of the current "standard of care" for secondary prevention.

Present and future molecular testing of lung carcinoma.

PubMed

Dacic, Sanja; Nikiforova, Marina N

2014-03-01

The rapid development of targeted therapies has tremendously changed clinical management of lung carcinoma patients and set the stage for similar developments in other tumor types. Many studies have been published in the past decade in search for the most acceptable method of assessment for predictors of response to targeted therapies in lung cancer. As a result, several guidelines for molecular testing have been published in a past couple of years. Because of accumulated evidence that targetable drugs show the best efficacy and improved progression survival rates in lung cancer patients whose tumors have a specific genotype, molecular testing for predictors of therapy response has became standard of care. Presently, testing for EGFR mutations and ALK rearrangements in lung adenocarcinoma has been standardized. The landscape of targetable genomic alterations in lung carcinoma is expanding, but none of other potentially targetable biomarkers have been standardized outside of clinical trials. This review will summarize current practice of molecular testing. Future methods in molecular testing of lung carcinoma will be briefly reviewed.

Novel and emerging nonpositive airway pressure therapies for sleep apnea.

PubMed

Park, John G; Morgenthaler, Timothy M; Gay, Peter C

2013-12-01

CPAP therapy has remained the standard of care for the treatment of sleep apnea for nearly 4 decades. Its overall effectiveness, however, has been limited by incomplete adherence despite many efforts to improve comfort. Conventional alternative therapies include oral appliances and upper airway surgeries. Recently, several innovative alternatives to CPAP have been developed. These novel approaches include means to increase arousal thresholds, electrical nerve stimulation, oral vacuum devices, and nasal expiratory resistive devices. We will review the physiologic mechanisms and the current evidence for these novel treatments.

Review of pharmacological therapies in fibromyalgia syndrome

PubMed Central

2014-01-01

This review addresses the current status of drug therapy for the management of fibromyalgia syndrome (FMS) and is based on interdisciplinary FMS management guidelines, meta-analyses of drug trial data, and observational studies. In the absence of a single gold-standard medication, patients are treated with a variety of drugs from different categories, often with limited evidence. Drug therapy is not mandatory for the management of FMS. Pregabalin, duloxetine, milnacipran, and amitriptyline are the current first-line prescribed agents but have had a mostly modest effect. With only a minority of patients expected to experience substantial benefit, most will discontinue therapy because of either a lack of efficacy or tolerability problems. Many drug treatments have undergone limited study and have had negative results. It is unlikely that these failed pilot trials will undergo future study. However, medications, though imperfect, will continue to be a component of treatment strategy for these patients. Both the potential for medication therapy to relieve symptoms and the potential to cause harm should be carefully considered in their administration. PMID:24433463

Music therapy for end-of-life care.

PubMed

Bradt, Joke; Dileo, Cheryl

2010-01-20

Music therapy in end-of-life care aims to improve a person's quality of life by helping relieve symptoms, addressing psychological needs, offering support, facilitating communication, and meeting spiritual needs. In addition, music therapists assist family and caregivers with coping, communication, and grief/bereavement. To examine effects of music therapy with standard care versus standard care alone or standard care combined with other therapies on psychological, physiological, and social responses in end-of-life care. We searched CENTRAL, MEDLINE, CINAHL, EMBASE, PSYCINFO, LILACS, CancerLit, Science Citation Index, www.musictherapyworld.de, CAIRSS for Music, Proquest Digital Dissertations, ClinicalTrials.gov, Current Controlled Trials, and the National Research Register to September 2009. We handsearched music therapy journals and reference lists, and contacted experts to identify unpublished manuscripts. There was no language restriction. We included all randomized and quasi-randomized controlled trials that compared music interventions and standard care with standard care alone or combined with other therapies in any care setting with a diagnosis of advanced life-limiting illness being treated with palliative intent and with a life expectancy of less than two years. Data were extracted, and methodological quality was assessed, independently by review authors. Additional information was sought from study authors when necessary. Results are presented using weighted mean differences for outcomes measured by the same scale and standardized mean differences for outcomes measured by different scales. Posttest scores were used. In cases of statistically significant baseline difference, we used change scores. Five studies (175 participants) were included. There is insufficient evidence of high quality to support the effect of music therapy on quality of life of people in end-of-life care. Given the limited number of studies and small sample sizes, more research is needed.No strong evidence was found for the effect of music therapy on pain or anxiety.These results were based on two small studies. There were insufficient data to examine the effect of music therapy on other physical, psychological, or social outcomes. A limited number of studies suggest there may be a benefit of music therapy on the quality of life of people in end-of-life care. However, the results stem from studies with a high risk of bias. More research is needed.

Esophageal cancer: The latest on chemoprevention and state of the art therapies.

PubMed

Le Bras, Gregoire F; Farooq, Muhammad H; Falk, Gary W; Andl, Claudia D

2016-11-01

Esophageal cancer is currently the 8th most common cancer worldwide and the 6th leading cause of cancer-related mortality. Despite remarkable advances, the mortality for those suffering from esophageal cancer remains high, with 5-year survival rates of less than 20%. In part, because most patients present with late-stage disease, long-term survival even after resection and therapy is disappointingly low. As we will discuss in this review, multiple characteristics specific to the disease stage and patient must be considered when choosing a treatment plan. This article will summarize current standard therapies, potential application of chemoprevention drugs and the promise and partial failure of personalized medicine, as well as novel treatments addressing this disease. Copyright © 2016 Elsevier Ltd. All rights reserved.

Cutaneous wound healing: Current concepts and advances in wound care

PubMed Central

Klein, Kenneth C; Guha, Somes Chandra

2014-01-01

A non-healing wound is defined as showing no measurable signs of healing for at least 30 consecutive treatments with standard wound care.[1] It is a snapshot of a patient's total health as well as the ongoing battle between noxious factors and the restoration of optimal macro and micro circulation, oxygenation and nutrition. In practice, standard therapies for non-healing cutaneous wounds include application of appropriate dressings, periodic debridement and eliminating causative factors.[2] The vast majority of wounds would heal by such approach with variable degrees of residual morbidity, disability and even mortality. Globally, beyond the above therapies, newer tools of healing are selectively accessible to caregivers, for various logistical or financial reasons. Our review will focus on the use of hyperbaric oxygen therapy (HBOT), as used at our institution (CAMC), and some other modalities that are relatively accessible to patients. HBOT is a relatively safe and technologically simpler way to deliver care worldwide. However, the expense for including HBOT as standard of care for recognized indications per UHMS(Undersea and Hyperbaric Medical Society) may vary widely from country to country and payment system.[3] In the USA, CMS (Centers for Medicare and Medicaid Services) approved indications for HBOT vary from that of the UHMS for logistical reasons.[1] We shall also briefly look into other newer therapies per current clinical usage and general acceptance by the medical community. Admittedly, there would be other novel tools with variable success in wound healing worldwide, but it would be difficult to include all in this treatise. PMID:25593414

How to engage the right brain hemisphere in aphasics without even singing: evidence for two paths of speech recovery

PubMed Central

Stahl, Benjamin; Henseler, Ilona; Turner, Robert; Geyer, Stefan; Kotz, Sonja A.

2012-01-01

There is an ongoing debate as to whether singing helps left-hemispheric stroke patients recover from non-fluent aphasia through stimulation of the right hemisphere. According to recent work, it may not be singing itself that aids speech production in non-fluent aphasic patients, but rhythm and lyric type. However, the long-term effects of melody and rhythm on speech recovery are largely unknown. In the current experiment, we tested 15 patients with chronic non-fluent aphasia who underwent either singing therapy, rhythmic therapy, or standard speech therapy. The experiment controlled for phonatory quality, vocal frequency variability, pitch accuracy, syllable duration, phonetic complexity and other influences, such as the acoustic setting and learning effects induced by the testing itself. The results provide the first evidence that singing and rhythmic speech may be similarly effective in the treatment of non-fluent aphasia. This finding may challenge the view that singing causes a transfer of language function from the left to the right hemisphere. Instead, both singing and rhythmic therapy patients made good progress in the production of common, formulaic phrases—known to be supported by right corticostriatal brain areas. This progress occurred at an early stage of both therapies and was stable over time. Conversely, patients receiving standard therapy made less progress in the production of formulaic phrases. They did, however, improve their production of non-formulaic speech, in contrast to singing and rhythmic therapy patients, who did not. In light of these results, it may be worth considering the combined use of standard therapy and the training of formulaic phrases, whether sung or rhythmically spoken. Standard therapy may engage, in particular, left perilesional brain regions, while training of formulaic phrases may open new ways of tapping into right-hemisphere language resources—even without singing. PMID:23450277

The evolving role of stereotactic radiosurgery and stereotactic radiation therapy for patients with spine tumors.

PubMed

Rock, Jack P; Ryu, Samuel; Yin, Fang-Fang; Schreiber, Faye; Abdulhak, Muwaffak

2004-01-01

Traditional management strategies for patients with spinal tumors have undergone considerable changes during the last 15 years. Significant improvements in digital imaging, computer processing, and treatment planning have provided the basis for the application of stereotactic techniques, now the standard of care for intracranial pathology, to spinal pathology. In addition, certain of these improvements have also allowed us to progress from frame-based to frameless systems which now act to accurately assure the delivery of high doses of radiation to a precisely defined target volume while sparing injury to adjacent normal tissues. In this article we will describe the evolution from yesterday's standards for radiation therapy to the current state of the art for the treatment of patients with spinal tumors. This presentation will include a discussion of radiation dosing and toxicity, the overall process of extracranial radiation delivery, and the current state of the art regarding Cyberknife, Novalis, and tomotherapy. Additional discussion relating current research protocols and future directions for the management of benign tumors of the spine will also be presented.

Gene therapy for haemophilia.

PubMed

Sharma, Akshay; Easow Mathew, Manu; Sriganesh, Vasumathi; Neely, Jessica A; Kalipatnapu, Sasank

2014-11-14

Haemophilia is a genetic disorder which is characterized by spontaneous or provoked, often uncontrolled, bleeding into joints, muscles and other soft tissues. Current methods of treatment are expensive, challenging and involve regular administration of clotting factors. Gene therapy has recently been prompted as a curative treatment modality. To evaluate the safety and efficacy of gene therapy for treating people with haemophilia A or B. We searched the Cochrane Cystic Fibrosis & Genetic Disorders Group's Coagulopathies Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched the reference lists of relevant articles and reviews.Date of last search: 06 November 2014. Eligible trials included randomised or quasi-randomised clinical trials, including controlled clinical trials comparing gene therapy (with or without standard treatment) with standard treatment (factor replacement) or other 'curative' treatment such as stem cell transplantation individuals with haemophilia A or B of all ages who do not have inhibitors to factor VIII or IX. No trials of gene therapy for haemophilia were found. No trials of gene therapy for haemophilia were identified. No randomised or quasi-randomised clinical trials of gene therapy for haemophilia were identified. Thus, we are unable to determine the effects of gene therapy for haemophilia. Gene therapy for haemophilia is still in its nascent stages and there is a need for well-designed clinical trials to assess the long-term feasibility, success and risks of gene therapy for people with haemophilia.

Chemotherapy and targeted therapy in advanced biliary tract carcinoma: a pooled analysis of clinical trials.

PubMed

Eckel, Florian; Schmid, Roland M

2014-01-01

In biliary tract cancer, gemcitabine platinum (GP) doublet palliative chemotherapy is the current standard treatment. The aim of this study was to analyze recent trials, even those small and nonrandomized, and identify superior new regimens. Trials published in English between January 2000 and January 2014 were analyzed, as well as ASCO abstracts from 2010 to 2013. In total, 161 trials comprising 6,337 patients were analyzed. The pooled results of standard therapy GP (no fluoropyrimidine, F, or other drug) were as follows: the median response rate (RR), tumor control rate (TCR), time to tumor progression (TTP) and overall survival (OS) were 25.9 and 63.5%, and 5.3 and 9.5 months, respectively. GFP triplets as well as G-based chemotherapy plus targeted therapy were significantly superior to GP concerning tumor control (TCR, TTP) and OS, with no difference in RR. Triplet combinations of GFP as well as G-based chemotherapy with (predominantly EGFR) targeted therapy are most effective concerning tumor control and survival.

Music therapy for end-of-life care: An updated systematic review.

PubMed

McConnell, Tracey; Scott, David; Porter, Sam

2016-10-01

Music therapy during palliative and end-of-life care is well established and positive benefits for patients have been reported. Assess the effectiveness of music therapy versus standard care alone or standard care in combination with other therapies for improving psychological, physiological and social outcomes among adult patients in any palliative care setting. In order to update an existing Cochrane systematic review, we searched MEDLINE, CINAHL, EMBASE, PsycINFO, CENTRAL, ClinicalTrials.gov register and Current Controlled Trials register to identify randomised or quasi-randomised controlled trials published between 2009 and April 2015. Nine electronic music therapy journals were searched from 2009 until April 2015, along with reference lists and contact was made with key experts in music therapy. Only studies published in English were eligible for inclusion. Two reviewers independently screened titles, abstracts, assessed relevant studies for eligibility, extracted data and judged risk of bias for included studies. Disagreements were resolved through discussion with a third reviewer. Data were synthesised in Revman using the random effects model. Heterogeneity was assessed using I(2). Three studies were included in the review. Findings suggest that music therapy may be effective for helping to reduce pain in palliative care patients (standard mean deviation = -0.42, 95% confidence interval = -0.68 to -0.17, p = 0.001). Available evidence did not support the use of music therapy to improve overall quality of life in palliative care. While this review suggests that music therapy may be effective for reducing pain, this is based on studies with a high risk of bias. Further high-quality research is required. © The Author(s) 2016.

Antibody-mediated delivery of therapeutics for cancer therapy.

PubMed

Parakh, Sagun; Parslow, Adam C; Gan, Hui K; Scott, Andrew M

2016-01-01

Antibody-conjugated therapies (ACTs) combine the specificity of monoclonal antibodies to target cancer cells directly with highly potent payloads, often resulting in superior efficacy and/or reduced toxicity. This represents a new approach to the treatment of cancer. There have been highly promising clinical trial results using this approach with improvements in linker and payload technology. The breadth of current trials examining ACTs in haematological malignancies and solid tumours indicate the potential for clinical impact. This review will provide an overview of ACTs currently in clinical development as well as the principles of antibody delivery and types of payloads used, including cytotoxic drugs, radiolabelled isotopes, nanoparticle-based siRNA particles and immunotoxins. The focus of much of the clinical activity in ACTs has, understandably, been on their use as a monotherapy or in combination with standard of care drugs. This will continue, as will the search for better targets, linkers and payloads. Increasingly, as these drugs enter routine clinical care, important questions will arise regarding how to optimise ACT treatment approaches, including investigation of resistance mechanisms, biomarker and patient selection strategies, understanding of the unique toxicities of these drugs, and combinatorial approaches with standard therapies as well as emerging therapeutic agents like immunotherapy.

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

Mahesh, M; Borras, C; Frey, G

This workshop is jointly organized by the AAPM, the Spanish (SEFM) and the Russian (AMPR) Medical Physics Societies, as part of formal educational exchange agreements signed by the AAPM with each one of these two societies.With the rapid technological advances in radiation therapy both for treatment and imaging, it is challenging how physics is taught to medical physicists practicing in radiation therapy. The main Objectives: of this workshop is to bring forth current status, challenges and issues related to education of radiation therapy physicists here in the US, Spain and Russia. Medical physicists from each one of these countries willmore » present educational requirements of international recommendations and directives and analyze their impact on national legislations. Current and future educational models and plans for harmonization will be described. The role of universities, professional societies and examination boards, such as the American Board of Radiology, will be discussed. Minimum standards will be agreed upon. Learning Objectives: Review medical physics educational models supported by AAPM, SEFM, and AMPR. Discuss the role of governmental and non-governmental organizations in elaborating and adopting medical physics syllabi. Debate minimum educational standards for medical physics education based on country-specific resources.« less

Modern retinal laser therapy

PubMed Central

Kozak, Igor; Luttrull, Jeffrey K.

2014-01-01

Medicinal lasers are a standard source of light to produce retinal tissue photocoagulation to treat retinovascular disease. The Diabetic Retinopathy Study and the Early Treatment Diabetic Retinopathy Study were large randomized clinical trials that have shown beneficial effect of retinal laser photocoagulation in diabetic retinopathy and have dictated the standard of care for decades. However, current treatment protocols undergo modifications. Types of lasers used in treatment of retinal diseases include argon, diode, dye and multicolor lasers, micropulse lasers and lasers for photodynamic therapy. Delivery systems include contact lens slit-lamp laser delivery, indirect ophthalmocope based laser photocoagulation and camera based navigated retinal photocoagulation with retinal eye-tracking. Selective targeted photocoagulation could be a future alternative to panretinal photocoagulation. PMID:25892934

Proton Therapy for Head and Neck Cancer.

PubMed

Kim, Joseph K; Leeman, Jonathan E; Riaz, Nadeem; McBride, Sean; Tsai, Chiaojung Jillian; Lee, Nancy Y

2018-05-09

The application of proton beam radiation therapy in the treatment of head and neck cancer has grown tremendously in the past few years. Globally, widespread interest in proton beam therapy has led to multiple research efforts regarding its therapeutic value and cost-effectiveness. The current standard of care using modern photon radiation technology has demonstrated excellent treatment outcomes, yet there are some situations where disease control remains suboptimal with the potential for detrimental acute and chronic toxicities. Due to the advantageous physical properties of the proton beam, proton beam therapy may be superior to photon therapy in some patient subsets for both disease control and patient quality of life. As enthusiasm and excitement for proton beam therapy continue to increase, clinical research and widespread adoption will elucidate the true value of proton beam therapy and give a greater understanding of the full risks and benefits of proton therapy in head and neck cancer.

Stem Cell Therapies for Treating Diabetes: Progress and Remaining Challenges.

PubMed

Sneddon, Julie B; Tang, Qizhi; Stock, Peter; Bluestone, Jeffrey A; Roy, Shuvo; Desai, Tejal; Hebrok, Matthias

2018-06-01

Restoration of insulin independence and normoglycemia has been the overarching goal in diabetes research and therapy. While whole-organ and islet transplantation have become gold-standard procedures in achieving glucose control in diabetic patients, the profound lack of suitable donor tissues severely hampers the broad application of these therapies. Here, we describe current efforts aimed at generating a sustainable source of functional human stem cell-derived insulin-producing islet cells for cell transplantation and present state-of-the-art efforts to protect such cells via immune modulation and encapsulation strategies. Copyright © 2018. Published by Elsevier Inc.

Augmented post-remission therapy for a minimal residual disease-defined high-risk subgroup of children and young people with clinical standard-risk and intermediate-risk acute lymphoblastic leukaemia (UKALL 2003): a randomised controlled trial.

PubMed

Vora, Ajay; Goulden, Nick; Mitchell, Chris; Hancock, Jeremy; Hough, Rachael; Rowntree, Clare; Moorman, Anthony V; Wade, Rachel

2014-07-01

No randomised study has shown whether stratification of treatment by minimal residual disease (MRD) response improves outcome in children and young people with acute lymphoblastic leukaemia (ALL). We assessed whether children and young people with clinical standard and intermediate-risk ALL who have persistent MRD at the end of induction therapy benefit from augmented post-remission therapy. Between Oct 1, 2003, and June 30, 2011, we enrolled eligible patients aged 1-24 years and initially categorised them into clinical standard-risk, intermediate-risk, and high-risk groups on the basis of a combination of National Cancer Institute criteria, cytogenetics, and early morphological response to induction therapy. Clinical standard-risk and intermediate-risk patients with MRD of 0·01% or higher at day 29 of induction (MRD high risk) were randomly assigned (1:1) to standard therapy (treatment regimens A and B) or augmented post-remission therapy (regimen C). Compared with standard therapy, the augmented treatment regimen (regimen C) included an additional eight doses of pegylated asparaginase, 18 doses of vincristine, and escalated-dose intravenous methotrexate without folinic acid rescue during interim maintenance courses. Computer randomisation was used for treatment allocation and was balanced for sex, age (<10 years vs ≥10 years), and white blood cell count at diagnosis (<50 × 10(9)/L vs ≥50 × 10(9)/L) by minimisation. Patients, clinicians, and data analysts were not masked to treatment allocation. The primary outcomes were event-free survival and overall survival. Analyses were by intention to treat. This trial is registered with Current Controlled Trials, number ISRCTN07355119. 533 MRD high-risk patients were randomly assigned to receive standard (n=266) or augmented (n=267) post-remission therapy. After a median follow-up of 70 months (IQR 52-91), 5-year event-free survival was better in the augmented treatment group (89·6% [95% CI 85·9-93·3]) than in the standard group (82·8% [78·1-87·5]; odds ratio [OR] 0·61 [95% CI 0·39-0·98], p=0·04). Overall survival at 5 years was numerically, but not significantly, higher in the augmented treatment group (92·9% [95% CI 89·8-96·0]) than in the standard therapy group (88·9% [85·0-92·8]; OR 0·67 [95% CI 0·38-1·17], p=0·16). More adverse events occurred in the augmented treatment group than in the standard group (asparaginase-related hypersensitivity in 18 [6·7%] in the augmented group vs two [0·8%] in the standard group and asparaginase-related pancreatitis in eight [3·0%] vs one [0·4%]; intravenous methotrexate-related mucositis in 11 [4·1%] vs three [1·1%] and methotrexate-related stomatitis in 48 [18·0%] vs 12 [4·5%]). Our findings suggest that children and young people with acute lymphoblastic leukaemia and 0·01% or more MRD at the end of remission induction therapy could benefit from augmented post-remission therapy. However, the asparaginase and intravenous methotrexate used in the augmented treatment regimen is associated with more adverse events than is the standard post-remission treatment regimen. Medical Research Council and Leukaemia and Lymphoma Research. Copyright © 2014 Elsevier Ltd. All rights reserved.

Clostridium difficile infection in patients with inflammatory bowel disease

PubMed Central

Saidel-Odes, Lisa; Borer, Abraham; Odes, Selwyn

2011-01-01

Clostridium difficile infection in patients with inflammatory bowel disease has become a serious clinical problem over the past few years. This review is focused on the current changes in epidemiology, pertinent clinical aspects, standard and newer diagnostic methods, established and novel therapies, and prevention of infection. There is emphasis on the importance of clinical awareness, rapid detection by stool testing, and appropriate antibiotic therapy, while newer technologies, antibiotics and other treatments are explored. PMID:24713726

[Pediatric ependymomas: Current diagnosis and therapy].

PubMed

Frappaz, Didier; Vasiljevic, Alexandre; Beuriat, Pierre-Aurelien; Alapetite, Claire; Grill, Jacques; Szathmari, Alexandru; Faure-Conter, Cécile

2016-10-01

Ependymomas represent 10% of pediatric brain tumors. In the recent WHO 2016 classification, pathology is enriched by localization and molecular biology. Whatever the age, total removal by one or several looks when required remains a major prognostic factor. In children, focal radiation remains a standard, while the role of chemotherapy is matter of randomized studies. In infants, front line chemotherapy is the standard. Inclusion in the SIOP ependymoma II protocol is encouraged. In case of relapse, further surgery and radiation are advised, while inclusion in innovative trials including re-irradiation, and phase I-II should be encouraged. A better understanding of underlying mechanisms of ependymoma cell will provide in the close future, the key to use targeted therapies at time of relapse, and very soon as first line therapy for some subgroups of patients. Copyright © 2016 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

Synergizing Radiation Therapy and Immunotherapy for Curing Incurable Cancers: Opportunities and Challenges

PubMed Central

Hodge, James W.; Guha, Chandan; Neefjes, Jacques; Gulley, James L.

2012-01-01

The combination of radiation therapy and immunotherapy holds particular promise as a strategy for cancer therapeutics. There is evidence that immunotherapy is most beneficial alone when employed early in the disease process or in combination with standard therapies (e.g., radiation) later in the disease process. Indeed, radiation may act synergistically with immunotherapy to enhance immune responses, inhibit immunosuppression, and/or alter the phenotype of tumor cells, thus rendering them more susceptible to immune-mediated killing. Furthermore, as monotherapies, both immunotherapy and radiation may be insufficient to eliminate tumor masses. However, following immunization with a cancer vaccine, the destruction of even a small percentage of tumor cells by radiation could result in cross-priming and presentation of tumor antigens to the immune system, thereby potentiating antitumor responses. Learning how to exploit radiation-induced changes to tumor-cell antigens, and how to induce effective immune responses to these cumulatively immunogenic stimuli, is an exciting frontier in cancer therapy research. This review examines a) mechanisms by which many forms of radiation therapy can induce or augment antitumor immune responses and b) preclinical systems that demonstrate that immunotherapy can be effectively combined with radiation therapy. Finally, we review current clinical trials where standard-of-care radiation therapy is being combined with immunotherapy. PMID:18777956

Music therapy for mood disturbance during hospitalization for autologous stem cell transplantation: a randomized controlled trial.

PubMed

Cassileth, Barrie R; Vickers, Andrew J; Magill, Lucanne A

2003-12-15

High-dose therapy with autologous stem cell transplantation (HDT/ASCT) is a commonly used treatment for hematologic malignancies. The procedure causes significant psychological distress and no interventions have been demonstrated to improve mood in these patients. Music therapy has been shown to improve anxiety in a variety of acute medical settings. In the current study, the authors determined the effects of music therapy compared with standard care on mood during inpatient stays for HDT/ASCT. Patients with hematologic malignancy admitted for HDT/ASCT at two sites (Memorial Sloan-Kettering Cancer Center and Ireland Cancer Center in Cleveland, Ohio) were randomized to receive music therapy given by trained music therapists or standard care. Outcome was assessed at baseline and every 3 days after randomization using the Profile of Mood States. Of 69 patients registered in the study, follow-up data were available for 62 (90%). During their inpatient stay, patients in the music therapy group scored 28% lower on the combined Anxiety/Depression scale (P = 0.065) and 37% lower (P = 0.01) on the total mood disturbance score compared with controls. Music therapy is a noninvasive and inexpensive intervention that appears to reduce mood disturbance in patients undergoing HDT/ASCT. Copyright 2003 American Cancer Society.

Clinical Translation of Cell Therapy, Tissue Engineering, and Regenerative Medicine Product in Malaysia and Its Regulatory Policy.

PubMed

Bt Hj Idrus, Ruszymah; Abas, Arpah; Ab Rahim, Fazillahnor; Saim, Aminuddin Bin

2015-12-01

With the worldwide growth of cell and tissue therapy (CTT) in treating diseases, the need of a standardized regulatory policy is of paramount concern. Research in CTT in Malaysia has reached stages of clinical trials and commercialization. In Malaysia, the regulation of CTT is under the purview of the National Pharmaceutical Control Bureau (NPCB), Ministry of Health (MOH). NPCB is given the task of regulating CTT, under a new Cell and Gene Therapy Products framework, and the guidelines are currently being formulated. Apart from the laboratory accreditation, researchers are advised to follow Guidelines for Stem Cell Research and Therapy from the Medical Development Division, MOH, published in 2009.

Clinical Translation of Cell Therapy, Tissue Engineering, and Regenerative Medicine Product in Malaysia and Its Regulatory Policy

PubMed Central

Abas, Arpah; Ab Rahim, Fazillahnor; Saim, Aminuddin Bin

2015-01-01

With the worldwide growth of cell and tissue therapy (CTT) in treating diseases, the need of a standardized regulatory policy is of paramount concern. Research in CTT in Malaysia has reached stages of clinical trials and commercialization. In Malaysia, the regulation of CTT is under the purview of the National Pharmaceutical Control Bureau (NPCB), Ministry of Health (MOH). NPCB is given the task of regulating CTT, under a new Cell and Gene Therapy Products framework, and the guidelines are currently being formulated. Apart from the laboratory accreditation, researchers are advised to follow Guidelines for Stem Cell Research and Therapy from the Medical Development Division, MOH, published in 2009. PMID:26192075

Clinical Cell Therapy Guidelines for Neurorestoration (IANR/CANR 2017)

PubMed Central

Huang, Hongyun; Young, Wise; Chen, Lin; Feng, Shiqing; Zoubi, Ziad M. Al; Sharma, Hari Shanker; Saberi, Hooshang; Moviglia, Gustavo A.; He, Xijing; Muresanu, Dafin F.; Sharma, Alok; Otom, Ali; Andrews, Russell J.; Al-Zoubi, Adeeb; Bryukhovetskiy, Andrey S.; Chernykh, Elena R.; Domańska-Janik, Krystyna; Jafar, Emad; Johnson, W. Eustace; Li, Ying; Li, Daqing; Luan, Zuo; Mao, Gengsheng; Shetty, Ashok K.; Siniscalco, Dario; Skaper, Stephen; Sun, Tiansheng; Wang, Yunliang; Wiklund, Lars; Xue, Qun; You, Si-Wei; Zheng, Zuncheng; Dimitrijevic, Milan R.; Masri, W. S. El; Sanberg, Paul R.; Xu, Qunyuan; Luan, Guoming; Chopp, Michael; Cho, Kyoung-Suok; Zhou, Xin-Fu; Wu, Ping; Liu, Kai; Mobasheri, Hamid; Ohtori, Seiji; Tanaka, Hiroyuki; Han, Fabin; Feng, Yaping; Zhang, Shaocheng; Lu, Yingjie; Zhang, Zhicheng; Rao, Yaojian; Tang, Zhouping; Xi, Haitao; Wu, Liang; Shen, Shunji; Xue, Mengzhou; Xiang, Guanghong; Guo, Xiaoling; Yang, Xiaofeng; Hao, Yujun; Hu, Yong; Li, Jinfeng; AO, Qiang; Wang, Bin; Zhang, Zhiwen; Lu, Ming; Li, Tong

2018-01-01

Cell therapy has been shown to be a key clinical therapeutic option for central nervous system diseases or damage. Standardization of clinical cell therapy procedures is an important task for professional associations devoted to cell therapy. The Chinese Branch of the International Association of Neurorestoratology (IANR) completed the first set of guidelines governing the clinical application of neurorestoration in 2011. The IANR and the Chinese Association of Neurorestoratology (CANR) collaborated to propose the current version “Clinical Cell Therapy Guidelines for Neurorestoration (IANR/CANR 2017)”. The IANR council board members and CANR committee members approved this proposal on September 1, 2016, and recommend it to clinical practitioners of cellular therapy. These guidelines include items of cell type nomenclature, cell quality control, minimal suggested cell doses, patient-informed consent, indications for undergoing cell therapy, contraindications for undergoing cell therapy, documentation of procedure and therapy, safety evaluation, efficacy evaluation, policy of repeated treatments, do not charge patients for unproven therapies, basic principles of cell therapy, and publishing responsibility. PMID:29637817

The development of hematopoietic and mesenchymal stem cell transplantation as an effective treatment for multiple sclerosis

PubMed Central

Holloman, Jameson P; Ho, Calvin C; Hukki, Arushi; Huntley, Jennifer L; Gallicano, G Ian

2013-01-01

This article examines the current use and future implications of stem cell therapy in treating Multiple Sclerosis (MS). MS is the most common neurological disease in young adults, affecting approximately two million people worldwide. Currently there is no cure for MS. The standard treatment of MS involves disease-modifying drugs, which work to alleviate the symptoms of MS. However, these drugs carry adverse side effects and are ineffective in preventing disease progression in many MS patients. Hematopoietic stem cell transplantation (HSCT) was first used in 1995 to treat patients with severe rapidly progressing MS. The HSCT treatment protocol has evolved into a less intense conditioning regimen that is currently demonstrating efficacy in treating patients with variable disease severity—with best results in early-stage rapidly progressing MS patients with active CNS inflammation. Mesenchymal stem cell therapy (MSCT) is an experimental stem cell therapy currently undergoing clinical trials. Animal models and early clinical trials have shown promise that MSCT might be a low risk treatment to precipitate neuroregeneration and immunomodulation in MS patients. Specifically, neuroprogenitor and placental-derived mesenchymal stem cells offer the best hope for a practical treatment for MS. Stem cell therapy, and perhaps a combinatorial therapeutic approach, holds promise for a better treatment for MS. PMID:23862098

Targeting CPS1 in the treatment of Carbamoyl phosphate synthetase 1 (CPS1) deficiency, a urea cycle disorder.

PubMed

Diez-Fernandez, Carmen; Häberle, Johannes

2017-04-01

Carbamoyl phosphate synthetase 1 (CPS1) deficiency (CPS1D) is a rare autosomal recessive urea cycle disorder (UCD), which can lead to life-threatening hyperammonemia. Unless promptly treated, it can result in encephalopathy, coma and death, or intellectual disability in surviving patients. Over recent decades, therapies for CPS1D have barely improved leaving the management of these patients largely unchanged. Additionally, in many cases, current management (protein-restriction and supplementation with citrulline and/or arginine and ammonia scavengers) is insufficient for achieving metabolic stability, highlighting the importance of developing alternative therapeutic approaches. Areas covered: After describing UCDs and CPS1D, we give an overview of the structure- function of CPS1. We then describe current management and potential novel treatments including N-carbamoyl-L-glutamate (NCG), pharmacological chaperones, and gene therapy to treat hyperammonemia. Expert opinion: Probably, the first novel CPS1D therapies to reach the clinics will be the already commercial substance NCG, which is the standard treatment for N-acetylglutamate synthase deficiency and has been proven to rescue specific CPS1D mutations. Pharmacological chaperones and gene therapy are under development too, but these two technologies still have key challenges to be overcome. In addition, current experimental therapies will hopefully add further treatment options.

Nonsurgical management of hypertrophic scars: evidence-based therapies, standard practices, and emerging methods.

PubMed

Atiyeh, Bishara S

2007-01-01

Hypertrophic scars, resulting from alterations in the normal processes of cutaneous wound healing, are characterized by proliferation of dermal tissue with excessive deposition of fibroblast-derived extracellular matrix proteins, especially collagen, over long periods, and by persistent inflammation and fibrosis. Hypertrophic scars are among the most common and frustrating problems after injury. As current aesthetic surgical techniques become more standardized and results more predictable, a fine scar may be the demarcating line between acceptable and unacceptable aesthetic results. However, hypertrophic scars remain notoriously difficult to eradicate because of the high recurrence rates and the incidence of side effects associated with available treatment methods. This review explores the various treatment methods for hypertrophic scarring described in the literature including evidence-based therapies, standard practices, and emerging methods, attempting to distinguish those with clearly proven efficiency from anecdotal reports about therapies of doubtful benefits while trying to differentiate between prophylactic measures and actual treatment methods. Unfortunately, the distinction between hypertrophic scar treatments and keloid treatments is not obvious in most reports, making it difficult to assess the efficacy of hypertrophic scar treatment.

Electric field characteristics of electroconvulsive therapy with individualized current amplitude: a preclinical study.

PubMed

Lee, Won Hee; Lisanby, Sarah H; Laine, Andrew F; Peterchev, Angel V

2013-01-01

This study examines the characteristics of the electric field induced in the brain by electroconvulsive therapy (ECT) with individualized current amplitude. The electric field induced by bilateral (BL), bifrontal (BF), right unilateral (RUL), and frontomedial (FM) ECT electrode configurations was computed in anatomically realistic finite element models of four nonhuman primates (NHPs). We generated maps of the electric field strength relative to an empirical neural activation threshold, and determined the stimulation strength and focality at fixed current amplitude and at individualized current amplitudes corresponding to seizure threshold (ST) measured in the anesthetized NHPs. The results show less variation in brain volume stimulated above threshold with individualized current amplitudes (16-36%) compared to fixed current amplitude (30-62%). Further, the stimulated brain volume at amplitude-titrated ST is substantially lower than that for ECT with conventional fixed current amplitudes. Thus individualizing the ECT stimulus current could compensate for individual anatomical variability and result in more focal and uniform electric field exposure across different subjects compared to the standard clinical practice of using high, fixed current for all patients.

New and emerging therapies for acute and chronic graft versus host disease

PubMed Central

Hill, LaQuisa; Alousi, Amin; Kebriaei, Partow; Mehta, Rohtesh; Rezvani, Katayoun; Shpall, Elizabeth

2017-01-01

Graft versus host disease (GVHD) remains a major cause of morbidity and mortality following allogeneic hematopoietic stem-cell transplantation (HSCT). Despite the use of prophylactic GVHD regimens, a significant proportion of transplant recipients will develop acute or chronic GVHD following HSCT. Corticosteroids are standard first-line therapy, but are only effective in roughly half of all cases with ~50% of patients going on to develop steroid-refractory disease, which increases the risk of nonrelapse mortality. While progress has been made with improvements in survival outcomes over time, corticosteroids are associated with significant toxicities, and many currently available salvage therapies are associated with increased immunosuppression, infectious complications, and potential loss of the graft versus leukemia (GVL) effect. Thus, there is an unmet need for development of newer treatment strategies for both acute and chronic GVHD to improve long-term post-transplant outcomes and quality of life for HSCT recipients. Here, we provide a concise review of major emerging therapies currently being studied in the treatment of acute and chronic GVHD. PMID:29317998

Therapy of gallstone disease: What it was, what it is, what it will be

PubMed Central

Portincasa, Piero; Ciaula, Agostino Di; Bonfrate, Leonilde; Wang, David QH

2012-01-01

Cholesterol gallstone disease is a common clinical condition influenced by genetic factors, increasing age, female gender, and metabolic factors. Although laparoscopic cholecystectomy is currently considered the gold standard in treating patients with symptomatic gallstones, new perspectives regarding medical therapy of cholelithiasis are currently under discussion, also taking into account the pathogenesis of gallstones, the natural history of the disease and the analysis of the overall costs of therapy. A careful selection of patients may lead to successful non-surgical therapy in symptomatic subjects with a functioning gallbladder harboring small radiolucent stones. The classical oral litholysis by ursodeoxycholic acid has been recently paralleled by new experimental observations, suggesting that cholesterol-lowering agents which inhibit cholesterol synthesis (statins) or intestinal cholesterol absorption (ezetimibe), or drugs acting on specific nuclear receptors involved in cholesterol and bile acid homeostasis, might be proposed as additional approaches for treating cholesterol gallstones. In this review we discuss old, recent and future perspectives on medical treatment of cholesterol cholelithiasis. PMID:22577615

42 CFR 484.55 - Condition of participation: Comprehensive assessment of patients.

Code of Federal Regulations, 2014 CFR

2014-10-01

...) Standard: Drug regimen review. The comprehensive assessment must include a review of all medications the patient is currently using in order to identify any potential adverse effects and drug reactions, including ineffective drug therapy, significant side effects, significant drug interactions, duplicate drug...

Treatment of severe lupus nephritis: the new horizon.

PubMed

Chan, Tak Mao

2015-01-01

Lupus nephritis is a common and severe manifestation of systemic lupus erythematosus, and an important cause of both acute kidney injury and end-stage renal disease. Despite its aggressive course, lupus nephritis is amenable to treatment in the majority of patients. The paradigm of immunosuppressive treatment for lupus nephritis has evolved over the past few decades from corticosteroids alone to corticosteroids combined with cyclophosphamide. Sequential treatment regimens using various agents have been formulated for induction and long-term maintenance therapy, and mycophenolate mofetil has emerged as a standard of care option for both induction and maintenance immunosuppressive treatment. The current era has witnessed the emergence of multiple novel therapeutic options, such as calcineurin inhibitors and biologic agents that target key pathogenetic mechanisms of lupus nephritis. Clinical outcomes have improved in parallel with these therapeutic advances. This Review discusses the evidence in support of current standard of care immunosuppressive treatments and emerging therapies, and describes their roles and relative merits in the management of patients with lupus nephritis.

Costs and utilities of manual therapy and orthopedic standard care for low-prioritized orthopedic outpatients of working age: a cost consequence analysis.

PubMed

Lilje, Stina C; Persson, Ulf B; Tangen, Stine T; Kåsamoen, Stine; Skillgate, Eva

2014-08-01

Treatment for musculoskeletal disorders in primary care in Sweden is generally initiated with advice and medication. Second-line therapy is physiotherapy and/or injection and radiography; third-line therapy is referral to an orthopedist. Manual therapy is not routine. It is a challenge to identify patients who benefit from treatment by different specialists. The current referral strategy probably contributes to long waiting lists in orthopedic departments, which is costly and implies prolonged suffering for the patients. The aim of this health economic evaluation was to compare costs and outcomes from naprapathic manual therapy (NMT) with orthopedic standard care for common, low-prioritized, nonsurgical musculoskeletal disorders, after second-line treatment. Diagnose Related Groups were used to define the costs, and the SF-36 was encoded to evaluate the outcomes in cost per quality adjusted life years gained. Results from a 12 months' follow-up showed significantly larger improvement for the NMT than for orthopedic standard care, significantly lower mean cost per patient; 5427 SEK (*Price level 2009; 1 Euro=106,213 SEK; 1 US Dollar=76,457 SEK) (95% confidence interval, 3693-7161) compared to14298 SEK (95% confidence interval, 8322-20,274), and more gains in outcomes in cost per quality adjusted life years per patient (0.066 compared with 0.026). Thus the result is "dominant." It is plausible that improved outcomes and reasonable cost savings for low-prioritized nonsurgical outpatients would be attainable if NMT were available as an additional standard care option in orthopedic outpatient clinics.

Current Approaches in the Treatment of Relapsed and Refractory Acute Myeloid Leukemia

PubMed Central

Ramos, Nestor R.; Mo, Clifton C.; Karp, Judith E.; Hourigan, Christopher S.

2015-01-01

The limited sensitivity of the historical treatment response criteria for acute myeloid leukemia (AML) has resulted in a different paradigm for treatment compared with most other cancers presenting with widely disseminated disease. Initial cytotoxic induction chemotherapy is often able to reduce tumor burden to a level sufficient to meet the current criteria for “complete” remission. Nevertheless, most AML patients ultimately die from their disease, most commonly as clinically evident relapsed AML. Despite a variety of available salvage therapy options, prognosis in patients with relapsed or refractory AML is generally poor. In this review, we outline the commonly utilized salvage cytotoxic therapy interventions and then highlight novel investigational efforts currently in clinical trials using both pathway-targeted agents and immunotherapy based approaches. We conclude that there is no current standard of care for adult relapsed or refractory AML other than offering referral to an appropriate clinical trial. PMID:25932335

Video Game Rehabilitation for Outpatient Stroke (VIGoROUS): protocol for a multi-center comparative effectiveness trial of in-home gamified constraint-induced movement therapy for rehabilitation of chronic upper extremity hemiparesis.

PubMed

Gauthier, Lynne V; Kane, Chelsea; Borstad, Alexandra; Strahl, Nancy; Uswatte, Gitendra; Taub, Edward; Morris, David; Hall, Alli; Arakelian, Melissa; Mark, Victor

2017-06-08

Constraint-Induced Movement therapy (CI therapy) is shown to reduce disability, increase use of the more affected arm/hand, and promote brain plasticity for individuals with upper extremity hemiparesis post-stroke. Randomized controlled trials consistently demonstrate that CI therapy is superior to other rehabilitation paradigms, yet it is available to only a small minority of the estimated 1.2 million chronic stroke survivors with upper extremity disability. The current study aims to establish the comparative effectiveness of a novel, patient-centered approach to rehabilitation utilizing newly developed, inexpensive, and commercially available gaming technology to disseminate CI therapy to underserved individuals. Video game delivery of CI therapy will be compared against traditional clinic-based CI therapy and standard upper extremity rehabilitation. Additionally, individual factors that differentially influence response to one treatment versus another will be examined. This protocol outlines a multi-site, randomized controlled trial with parallel group design. Two hundred twenty four adults with chronic hemiparesis post-stroke will be recruited at four sites. Participants are randomized to one of four study groups: (1) traditional clinic-based CI therapy, (2) therapist-as-consultant video game CI therapy, (3) therapist-as-consultant video game CI therapy with additional therapist contact via telerehabilitation/video consultation, and (4) standard upper extremity rehabilitation. After 6-month follow-up, individuals assigned to the standard upper extremity rehabilitation condition crossover to stand-alone video game CI therapy preceded by a therapist consultation. All interventions are delivered over a period of three weeks. Primary outcome measures include motor improvement as measured by the Wolf Motor Function Test (WMFT), quality of arm use for daily activities as measured by Motor Activity Log (MAL), and quality of life as measured by the Quality of Life in Neurological Disorders (NeuroQOL). This multi-site RCT is designed to determine comparative effectiveness of in-home technology-based delivery of CI therapy versus standard upper extremity rehabilitation and in-clinic CI therapy. The study design also enables evaluation of the effect of therapist contact time on treatment outcomes within a therapist-as-consultant model of gaming and technology-based rehabilitation. Clinicaltrials.gov, NCT02631850 .

Curricular Inclusion of Complementary and Alternative Medicine Content in Occupational Therapy Education in the United States.

PubMed

Bradshaw, Michelle L

2016-10-01

An exploratory, cross-sectional survey design was used to explore the extent to which CAM was included, what factors impacted its inclusion, topics and student learning outcomes covered, who taught the material, and what sources were used to prepare for delivering course content. While the vast majority of responding occupational therapy educators reported curricular inclusion of CAM, educational experiences for occupational therapy students varied widely. This overview of the curricular inclusion of CAM by faculty in occupational therapy programs in the United States indicated that many occupational therapy educators are responding to the demands of a more integrative healthcare system. Resolving ethical and pragmatic issues, providing faculty development opportunities, and standardizing student learning outcomes would align all stakeholders and mitigate ambiguities that currently exist surrounding the inclusion of CAM in occupational therapy education.

Gene therapy for haemophilia.

PubMed

Sharma, Akshay; Easow Mathew, Manu; Sriganesh, Vasumathi; Reiss, Ulrike M

2016-12-20

Haemophilia is a genetic disorder characterized by spontaneous or provoked, often uncontrolled, bleeding into joints, muscles and other soft tissues. Current methods of treatment are expensive, challenging and involve regular administration of clotting factors. Gene therapy has recently been prompted as a curative treatment modality. This is an update of a published Cochrane Review. To evaluate the safety and efficacy of gene therapy for treating people with haemophilia A or B. We searched the Cochrane Cystic Fibrosis & Genetic Disorders Group's Coagulopathies Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched the reference lists of relevant articles and reviews.Date of last search: 18 August 2016. Eligible trials include randomised or quasi-randomised clinical trials, including controlled clinical trials comparing gene therapy (with or without standard treatment) with standard treatment (factor replacement) or other 'curative' treatment such as stem cell transplantation for individuals with haemophilia A or B of all ages who do not have inhibitors to factor VIII or IX. No trials of gene therapy for haemophilia were found. No trials of gene therapy for haemophilia were identified. No randomised or quasi-randomised clinical trials of gene therapy for haemophilia were identified. Thus, we are unable to determine the safety and efficacy of gene therapy for haemophilia. Gene therapy for haemophilia is still in its nascent stages and there is a need for well-designed clinical trials to assess the long-term feasibility, success and risks of gene therapy for people with haemophilia.

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.

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.

SSAT maintenance of certification: literature review on gastroesophageal reflux disease and hiatal hernia.

PubMed

Soper, Nathaniel J

2011-08-01

This article reviews the current literature pertaining to the diagnosis and management of gastroesophageal reflux disease (GERD) and hiatal hernia. GERD is one of the most common gastrointestinal disorders in the USA. For effective management, a conclusive diagnosis must be made. Most patients are effectively managed by acid suppression therapy, whereas others require procedural treatment. Endoluminal treatment of GERD is an option, but long-term results of this therapy are unknown. The "gold standard" surgical treatment of GERD is laparoscopic Nissen fundoplication. Large hiatal hernias are difficult to manage with a relatively high rate of recurrent hiatal hernia. Whether or not to use mesh at the hiatus to decrease this occurrence is currently debatable.

Current and cutting-edge interventions for the treatment of obese patients.

PubMed

Vairavamurthy, Jenanan; Cheskin, Lawrence J; Kraitchman, Dara L; Arepally, Aravind; Weiss, Clifford R

2017-08-01

The number of people classified as obese, defined by the World Health Organization as having a body mass index ≥30, has been rising since the 1980s. Obesity is associated with comorbidities such as hypertension, diabetes mellitus, and nonalcoholic fatty liver disease. The current treatment paradigm emphasizes lifestyle modifications, including diet and exercise; however this approach produces only modest weight loss for many patients. When lifestyle modifications fail, the current "gold standard" therapy for obesity is bariatric surgery, including Roux-en-Y gastric bypass, sleeve gastrectomy, duodenal switch, and placement of an adjustable gastric band. Though effective, bariatric surgery can have severe short- and long-term complications. To fill the major gap in invasiveness between lifestyle modification and surgery, researchers have been developing pharmacotherapies and minimally invasive endoscopic techniques to treat obesity. Recently, interventional radiologists developed a percutaneous transarterial catheter-directed therapy targeting the hormonal function of the stomach. This review describes the current standard obesity treatments (including diet, exercise, and surgery), as well as newer endoscopic bariatric procedures and pharmacotherapies to help patients lose weight. We present data from two ongoing human trials of a new interventional radiology procedure for weight loss, bariatric embolization. Copyright © 2017 Elsevier B.V. All rights reserved.

Advancing nutritional therapy: A novel polymeric formulation attenuates intestinal inflammation in a murine colitis model and suppresses pro-inflammatory cytokine production in ex-vivo cultured inflamed colonic biopsies.

PubMed

Alhagamhmad, Moftah H; Lemberg, Daniel A; Day, Andrew S; Tan, Li-Zsa; Ooi, Chee Y; Krishnan, Usha; Gupta, Nitin; Munday, John S; Leach, Steven T

2017-04-01

Nutritional therapy is a viable therapeutic option for the treatment of Crohn disease (CD). Therefore improving nutritional therapy would greatly benefit CD patients. The aim of this study was to define the anti-inflammatory properties of a novel nutritional polymeric formula (PF) in comparison to a currently available standard PF. Dextran sodium sulfate (DSS) was utilized to induce colitis in C57BL/6 mice with mice randomized to receive either standard PF or novel PF in addition to control groups. Changes in body weight were recorded and colonic damage was assessed histologically and biochemically. Additional experiments were also included where the cytokine response of colonic biopsies from pediatric CD patients was measured following exposure to standard PF or novel PF. DSS induced significant body weight loss, morphological changes in the colon, increased myeloperoxidase (MPO) activity and up-regulated colonic mRNA expression of tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-12 and monocyte chemoattractant protein (MCP)-1, as well as associated histological changes. Other than histological damage, these inflammatory changes were reversed by both novel and standard PF. However, the novel PF, but not standard PF, completely suppressed TNF-α, IL-6 and IL-8 levels from cultured biopsies. Newly developed nutritional formula reproducibly ameliorated DSS-induced colitis in a murine model, although this response was not measurably different to standard PF. However, the novel PF was significantly superior in suppressing inflammatory cytokine release from cultured colonic biopsies. Collectively, these findings support a possible role for novel PF in advancing nutritional therapy for CD patients. Crown Copyright © 2016. Published by Elsevier Ltd. All rights reserved.

Cleveland Clinic experience with interstitial laser coagulation of the prostate

NASA Astrophysics Data System (ADS)

Ulchaker, James C.; Ng, Christopher S.; Palone, David; Angie, Michelle; Kursh, Elroy D.

2000-05-01

Transurethral resection of the prostate (TURP) has long been considered the gold standard therapy for benign prostatic hyperplasia (BPH). The problems associated with the TURP, which have been extensively described, include significant bleeding, TUR syndrome, incontinence, stricture, bladder neck contracture, and sexual dysfunction. The desire for simpler, less morbid alternative therapies to TURP has led to an eruption of research and development in the last decade. This is fueled by the continued research for more economical alternatives in our current high cost health care system.

[Automated procedure for volumetric measurement of metastases: estimation of tumor burden].

PubMed

Fabel, M; Bolte, H

2008-09-01

Cancer is a common and increasing disease worldwide. Therapy monitoring in oncologic patient care requires accurate and reliable measurement methods for evaluation of the tumor burden. RECIST (response evaluation criteria in solid tumors) and WHO criteria are still the current standards for therapy response evaluation with inherent disadvantages due to considerable interobserver variation of the manual diameter estimations. Volumetric analysis of e.g. lung, liver and lymph node metastases, promises to be a more accurate, precise and objective method for tumor burden estimation.

The race against the "septic shark"

PubMed Central

2015-01-01

Great white sharks are responsible for about 10 cases of death annually worldwide, as compared with millions of deaths caused by sepsis. However, the basic principles of avoiding shark attacks and fighting sepsis seem to be similar: avoidance, attention, and speed, if necessary. The present review discusses the current status of the systemic inflammatory response syndrome (SIRS) criteria, which are actually content for discussion because of their low specificity. Current data suggest that one in eight patients with severe sepsis does not fulfill the SIRS criteria and is consequently missed, and therefore the calls for new definitions of sepsis are getting louder. Furthermore, the need for early treatment of sepsis and fast admission to an intensive care unit (ICU) with experienced stuff is reviewed as well as the early and appropriate initiation of therapy, namely antibiotic and volume therapy. A key feature is the analysis of the studies from the so-called "Sepsis Trilogy" (ProCESS, ARISE, and ProMiSe studies), with a focus on the status of early goal-directed therapy (EGDT). The authors of the "Sepsis Trilogy" concluded that there is no benefit regarding survival in septic patients by using EGDT as compared with standard therapy. However, the low mortality of the control groups within the "Sepsis Trilogy" studies as compared with the Rivers et al. study from 2001 leads to the conclusion that there has been an improvement in the therapy of septic patients, most probably due to the early initiation of therapy as a kind of "standard" in sepsis therapy. Finally, the phenomenon of a "large trial disease" is discussed, exemplary in a trial which investigated the maintenance of the "right" mean arterial pressure in sepsis patients. Even if the result of a large randomized trial might be that there is no difference between two study groups, the real exercise is to identify the patient collectives who might benefit or experience harm due to an intervention. In summary, as compared with swimming in dangerous waters, high attention is needed in handling septic patients. Once an attack has occurred, speed is of utmost importance (i.e., initiation of therapy and admission to the ICU) because it appears logical that time is critical in septic patients This may have resulted in the implementation of early (goal-directed) treatment as a "standard" in the treatment of sepsis with significant improvement in survival. PMID:26728320

The race against the "septic shark".

PubMed

Westphal, Martin; Kampmeier, Tim

2015-01-01

Great white sharks are responsible for about 10 cases of death annually worldwide, as compared with millions of deaths caused by sepsis. However, the basic principles of avoiding shark attacks and fighting sepsis seem to be similar: avoidance, attention, and speed, if necessary. The present review discusses the current status of the systemic inflammatory response syndrome (SIRS) criteria, which are actually content for discussion because of their low specificity. Current data suggest that one in eight patients with severe sepsis does not fulfill the SIRS criteria and is consequently missed, and therefore the calls for new definitions of sepsis are getting louder. Furthermore, the need for early treatment of sepsis and fast admission to an intensive care unit (ICU) with experienced stuff is reviewed as well as the early and appropriate initiation of therapy, namely antibiotic and volume therapy. A key feature is the analysis of the studies from the so-called "Sepsis Trilogy" (ProCESS, ARISE, and ProMiSe studies), with a focus on the status of early goal-directed therapy (EGDT). The authors of the "Sepsis Trilogy" concluded that there is no benefit regarding survival in septic patients by using EGDT as compared with standard therapy. However, the low mortality of the control groups within the "Sepsis Trilogy" studies as compared with the Rivers et al. study from 2001 leads to the conclusion that there has been an improvement in the therapy of septic patients, most probably due to the early initiation of therapy as a kind of "standard" in sepsis therapy. Finally, the phenomenon of a "large trial disease" is discussed, exemplary in a trial which investigated the maintenance of the "right" mean arterial pressure in sepsis patients. Even if the result of a large randomized trial might be that there is no difference between two study groups, the real exercise is to identify the patient collectives who might benefit or experience harm due to an intervention. In summary, as compared with swimming in dangerous waters, high attention is needed in handling septic patients. Once an attack has occurred, speed is of utmost importance (i.e., initiation of therapy and admission to the ICU) because it appears logical that time is critical in septic patients This may have resulted in the implementation of early (goal-directed) treatment as a "standard" in the treatment of sepsis with significant improvement in survival.

Implications of technology in music therapy practice and research for music therapy education: a review of literature.

PubMed

Crowe, Barbara J; Rio, Robin

2004-01-01

This article reviews the use of technology in music therapy practice and research for the purpose of providing music therapy educators and clinicians with specific and accurate accounts of the types and benefits of technology being used in various settings. Additionally, this knowledge will help universities comply with National Association of Schools of Music requirements and help to standardize the education and training of music therapists in this rapidly changing area. Information was gathered through a literature review of music therapy and related professional journals and a wide variety of books and personal communications. More data were gathered in a survey requesting information on current use of technology in education and practice. This solicitation was sent to all American Music Therapy Association approved universities and clinical training directors. Technology applications in music therapy are organized according to the following categories: (a) adapted musical instruments, (b) recording technology, (c) electric/electronic musical instruments, (d) computer applications, (e) medical technology, (f) assistive technology for the disabled, and (g) technology-based music/sound healing practices. The literature reviewed covers 177 books and articles from a span of almost 40 years. Recommendations are made for incorporating technology into music therapy course work and for review and revision of AMTA competencies. The need for an all-encompassing clinical survey of the use of technology in current music therapy practice is also identified.

Attention-Deficit Hyperactivity Disorder: A Handbook for Diagnosis and Treatment. Fourth Edition

ERIC Educational Resources Information Center

Barkley, Russell A., Ed.

2014-01-01

Widely regarded as the standard clinical reference, this volume provides the best current knowledge about attention-deficit/hyperactivity disorder (ADHD) in children, adolescents, and adults. The field's leading authorities address all aspects of assessment, diagnosis, and treatment, including psychological therapies and pharmacotherapy. Core…

A Clinical Approach to Antioxidant Therapy: Hypertonic Fluid Resuscitation Trial

DTIC Science & Technology

2003-06-01

5 2. Experimental Section...limited forward surgical care and delayed evacuation.[9] 1.1.1 Current Fluid Resuscitation Standard of Care By virtue of clinical experience , low cost...bleeding, thereby potentially increasing mortality. Indeed, evidence from experimental animal studies suggests that small-volume hypotensive

Tissue Engineered Strategies for Skeletal Muscle Injury

PubMed Central

Longo, Umile Giuseppe; Loppini, Mattia; Berton, Alessandra; Spiezia, Filippo; Maffulli, Nicola; Denaro, Vincenzo

2012-01-01

Skeletal muscle injuries are common in athletes, occurring with direct and indirect mechanisms and marked residual effects, such as severe long-term pain and physical disability. Current therapy consists of conservative management including RICE protocol (rest, ice, compression and elevation), nonsteroidal anti-inflammatory drugs, and intramuscular corticosteroids. However, current management of muscle injuries often does not provide optimal restoration to preinjury status. New biological therapies, such as injection of platelet-rich plasma and stem-cell-based therapy, are appealing. Although some studies support PRP application in muscle-injury management, reasons for concern persist, and further research is required for a standardized and safe use of PRP in clinical practice. The role of stem cells needs to be confirmed, as studies are still limited and inconsistent. Further research is needed to identify mechanisms involved in muscle regeneration and in survival, proliferation, and differentiation of stem cells. PMID:25098362

Advances in targeted therapy for acute myeloid leukaemia.

PubMed

Kayser, Sabine; Levis, Mark J

2018-02-01

In the past few years, research in the underlying pathogenic mechanisms of acute myeloid leukaemia (AML) has led to remarkable advances in our understanding of the disease. Cytogenetic and molecular aberrations are the most important factors in determining response to chemotherapy as well as long-term outcome, but beyond prognostication are potential therapeutic targets. Our increased understanding of the pathogenesis of AML, facilitated by next-generation sequencing, has spurred the development of new compounds in the treatment of AML, particularly the creation of small molecules that target the disease on a molecular level. Various new agents, such as tyrosine kinase inhibitors, immune checkpoint inhibitors, monoclonal or bispecific T-cell engager antibodies, metabolic and pro-apoptotic agents are currently investigated within clinical trials. The highest response rates are often achieved when new molecularly targeted therapies are combined with standard chemotherapy. Presented here is an overview of novel therapies currently being evaluated in AML. © 2017 John Wiley & Sons Ltd.

Augmentation of anti-tumor immunity by adoptive T-cell transfer after allogeneic hematopoietic stem cell transplantation

PubMed Central

Bleakley, Marie; Turtle, Cameron J; Riddell, Stanley R

2012-01-01

Allogeneic hematopoietic stem cell transplantation (HCT) is currently the standard of care for most patients with high-risk acute leukemias and some other hematologic malignancies. Although HCT can be curative, many patients who undergo allogeneic HCT will later relapse. There is, therefore, a critical need for the development of novel post-HCT therapies for patients who are at high risk for disease recurrence following HCT. One potentially efficacious approach is adoptive T-cell immunotherapy, which is currently undergoing a renaissance that has been inspired by scientific insight into the key issues that impeded its previous clinical application. Translation of the next generation of adoptive T-cell therapies to the allogeneic HCT setting, using donor T cells of defined specificity and function, presents a unique set of challenges and opportunities. The challenges, progress and future of adoptive T-cell therapy following allogeneic HCT are discussed in this review. PMID:22992235

International survey of vestibular rehabilitation therapists by the Barany Society Ad Hoc Committee on Vestibular Rehabilitation Therapy.

PubMed

Cohen, Helen S; Gottshall, Kim R; Graziano, Mariella; Malmstrom, Eva-Maj; Sharpe, Margaret H

2009-01-01

The goal of this study was to determine how occupational and physical therapists learn about vestibular rehabilitation therapy, their educational backgrounds, referral patterns, and their ideas about entry-level and advanced continuing education in vestibular rehabilitation therapy. The Barany Society Ad Hoc Committee for Vestibular Rehabilitation Therapy invited therapists around the world to complete an E-mail survey. Participants were either known to committee members or other Barany Society members, known to other participants, identified from their self-listings on the Internet, or volunteered after reading notices published in publications read by therapists. Responses were received from 133 therapists in 19 countries. They had a range of educational backgrounds, practice settings, and referral patterns. Few respondents had had any training about vestibular rehabilitation during their professional entry-level education. Most respondents learned about vestibular rehabilitation from continuing education courses, interactions with their colleagues, and reading. All of them endorsed the concept of developing standards and educating therapists about vestibular anatomy and physiology, vestibular diagnostic testing, vestibular disorders and current intervention strategies. Therefore, the Committee recommends the development of international standards for education and practice in vestibular rehabilitation therapy.

Current and Emerging Therapies for Lupus Nephritis

PubMed Central

Parikh, Samir V.

2016-01-01

The introduction of corticosteroids and later, cyclophosphamide dramatically improved survival in patients with proliferative lupus nephritis, and combined administration of these agents became the standard-of-care treatment for this disease. However, treatment failures were still common and the rate of progression to ESRD remained unacceptably high. Additionally, treatment was associated with significant morbidity. Therefore, as patient survival improved, the goals for advancing lupus nephritis treatment shifted to identifying therapies that could improve long-term renal outcomes and minimize treatment-related toxicity. Unfortunately, progress has been slow and the current approaches to the management of lupus nephritis continue to rely on high-dose corticosteroids plus a broad-spectrum immunosuppressive agent. Over the past decade, an improved understanding of lupus nephritis pathogenesis fueled several clinical trials of novel drugs, but none have been found to be superior to the combination of a cytotoxic agent and corticosteroids. Despite these trial failures, efforts to translate mechanistic advances into new treatment approaches continue. In this review, we discuss current therapeutic strategies for lupus nephritis, briefly review recent advances in understanding the pathogenesis of this disease, and describe emerging approaches developed on the basis of these advances that promise to improve upon the standard-of-care lupus nephritis treatments. PMID:27283496

A win for the patient: Direct patient notification improves treatment rates of active Helicobacter pylori infection.

PubMed

Selvaratnam, Sriharan; Yeoh, Joey; Hsiang, John; Patrick, Alasdair B

2014-01-01

Current international guidelines recommend the commencement of effective eradication therapy as soon as active Helicobacter pylori (H. pylori) infection is confirmed. At our institution, all positive Campylobacter-like Organism (CLO) test results were automatically communicated to general practitioners (GPs) via a standardised letter, which also advised the commencement of eradication therapy. Despite this endeavour, a clinical audit conducted in 2011 demonstrated that only 66 per cent of confirmed H. pylori-positive South Auckland patients received eradication treatment and only 83 per cent of these patients received treatment within one month. Improve the timely initiation of H. pylori eradication therapy through direct patient notification. A prospective clinical audit of 109 consecutive outpatients with a positive CLO test identified at gastroscopy. In addition to standard general practitioner notification, patients were also directly notified of their positive CLO test result via a standardised letter, which provided information about H. pylori and its disease associations as well as advising patients to seek consultation with their GP to commence eradication therapy. Dispensing data was examined using Test Safe electronic records to determine the total uptake and timing of treatment compared to data from a preliminary 2011 audit. Ninety-five per cent of H. pylori-positive patients received standard triple therapy; therefore, treatment of active H. pylori infection was significantly higher when patients were directly notified in addition to standard GP notification, when compared to GP notification alone (95 per cent vs 66 per cent, p<0.001). All patients who received eradication therapy did so within one month of notification, a significant improvement compared to data from the previous audit in 2011 (100 per cent vs. 83 per cent, p<0.001). Direct patient notification using a standardised letter is a simple and economical strategy that significantly improves the timely initiation of eradication therapy for active H. pylori infection. This has since been integrated into standard practice at our District Health Board (DHB).

The Sleep Or Mood Novel Adjunctive therapy (SOMNA) trial: a study protocol for a randomised controlled trial evaluating an internet-delivered cognitive behavioural therapy program for insomnia on outcomes of standard treatment for depression in men.

PubMed

Cockayne, Nicole L; Christensen, Helen M; Griffiths, Kathleen M; Naismith, Sharon L; Hickie, Ian B; Thorndike, Frances P; Ritterband, Lee M; Glozier, Nick S

2015-02-05

Insomnia is a significant risk factor for depression onset, can result in more disabling depressive illness, and is a common residual symptom following treatment cessation that can increase the risk of relapse. Internet-based cognitive behavioural therapy for insomnia has demonstrated efficacy and acceptability to men who are less likely than women to seek help in standard care. We aim to evaluate whether internet delivered cognitive behavioural therapy for insomnia as an adjunct to a standard depression therapeutic plan can lead to improved mood outcomes. Male participants aged 50 years or more, meeting Diagnostic and Statistical Manual of Mental Disorders criteria for current Major Depressive Episode and/or Dysthymia and self-reported insomnia symptoms, will be screened to participate in a single-centre double-blind randomised controlled trial with two parallel groups involving adjunctive internet-delivered cognitive behavioural therapy for insomnia and an internet-based control program. The trial will consist of a nine-week insomnia intervention period with a six-month follow-up period. During the insomnia intervention period participants will have their depression management coordinated by a psychiatrist using standard guideline-based depression treatments. The study will be conducted in urban New South Wales, Australia, where 80 participants from primary and secondary care and direct from the local community will be recruited. The primary outcome is change in the severity of depressive symptoms from baseline to week 12. This study will provide evidence on whether a widely accessible, evidence-based, internet-delivered cognitive behavioural therapy for insomnia intervention can lead to greater improvements than standard treatment for depression alone, in a group who traditionally do not readily access psychotherapy. The study is designed to establish effect size, feasibility and processes associated with implementing e-health solutions alongside standard clinical care, to warrant undertaking a larger more definitive clinical trial. Australian and New Zealand Clinical Trials Registry ACTRN12612000985886 .

The Irish Helicobacter pylori Working Group consensus for the diagnosis and treatment of H. pylori infection in adult patients in Ireland.

PubMed

Smith, Sinead; Boyle, Breida; Brennan, Denise; Buckley, Martin; Crotty, Paul; Doyle, Maeve; Farrell, Richard; Hussey, Mary; Kevans, David; Malfertheiner, Peter; Megraud, Francis; Nugent, Sean; O'Connor, Anthony; O'Morain, Colm; Weston, Shiobhan; McNamara, Deirdre

2017-05-01

Irish eradication rates for Helicobacter pylori are decreasing and there is an increase in the prevalence of antibiotic-resistant bacteria. These trends call into question current management strategies. To establish an Irish Helicobacter pylori Working Group (IHPWG) to assess, revise and tailor current available recommendations. Experts in the areas of gastroenterology and microbiology were invited to join the IHPWG. Questions of relevance to diagnosis, first-line and rescue therapy were developed using the PICO system. A literature search was performed. The 'Grading of Recommendations Assessment, Development and Evaluation' approach was then used to rate the quality of available evidence and grade the resulting recommendations. Key resultant IHPWG statements (S), the strength of recommendation and quality of evidence include S8: standard triple therapy for 7 days' duration can no longer be recommended (strong and moderate). S9: 14 days of clarithromycin-based triple therapy with a high-dose proton pump inhibitor (PPI) is recommended as first-line therapy. Bismuth quadruple therapy for 14 days is an alternative if available (strong and moderate). S12: second-line therapy depends on the first-line treatment and should not be the same treatment. The options are (a) 14 days of levofloxacin-based therapy with high-dose PPI, (b) 14 days of clarithromycin-based triple therapy with high-dose PPI or (c) bismuth quadruple therapy for 14 days (strong and moderate). S13: culture and antimicrobial susceptibility testing should be performed following two treatment failures (weak and low/very low). These recommendations are intended to provide the most relevant current best-practice guidelines for the management of H. pylori infection in adults in Ireland.

Bridge to Removal: A Paradigm Shift for Left Ventricular Assist Device Therapy

PubMed Central

Selzman, Craig H.; Madden, Jesse L.; Healy, Aaron H.; McKellar, Stephen H.; Koliopoulou, Antigone; Stehlik, Josef; Drakos, Stavros G.

2014-01-01

Ventricular assist devices have become standard therapy for patients with advanced heart failure either as a bridge to transplantation or destination therapy. Despite the functional and biologic evidence of reverse cardiac remodeling, few patients actually proceed to myocardial recovery, and even fewer to the point of having their device explanted. An enhanced understanding of the biology and care of the mechanically supported patient has redirected focus on the possibility of using ventricular assist devices as a bridge to myocardial recovery and removal. Herein, we review the current issues and approaches to transforming myocardial recovery to a practical reality. PMID:25442985

[Role of rifaximin in the treatment of hepatic encephalopathy].

PubMed

Sanchez-Delgado, Jordi; Miquel, Mireia

2016-04-01

Hepatic encephalopathy (HE) is a frequent and serious complication of liver cirrhosis. In addition to correction of the precipitating factors, the most commonly used treatments are non-absorbable disaccharides and rifaximin. Many of the recommendations are based on current clinical practice and there are few randomized controlled trials. Currently, rifaximin should be initiated during an episode of EH if, after 24-48 hours of non-absorbable disaccharide therapy, there is no clinical improvement. In recurrent EH, it is advisable to add rifaximin in patients under non-absorbable disaccharide therapy who develop a new episode. Currently, standard treatment with rifaximin for minimal EH is not recommended. Rifaximin is effective in the acute treatment of overt encephalopathy and in preventing recurrence. Copyright © 2015 Elsevier España, S.L.U. and AEEH y AEG. All rights reserved.

Emerging therapeutic options in GERD.

PubMed

Woodland, Philip; Amarasinghe, Gehanjali; Sifrim, Daniel

2013-06-01

Gastroesophageal reflux disease (GERD) is a prevalent problem resulting in a high level of healthcare consultation and expenditure in the Western World. Although standard medical therapy (in the form of proton pump inhibitor drugs) is effective in the majority of cases, there remains a significant proportion who are refractory to treatment. In addition, surgical therapy (in the form of laparoscopic fundoplication) is not always effective, and in some can be associated with significant side-effects, particularly gas-bloat, flatulence and dysphagia. As such there remains an unmet need in GERD to develop new therapies for refractory cases, and to develop alternatives to fundoplication with fewer side-effects. This article discusses the current state of pharmacological and non-pharmacological emerging therapies for GERD. Copyright © 2013 Elsevier Ltd. All rights reserved.

Image-Guided Ablation of Adrenal Lesions

PubMed Central

Yamakado, Koichiro

2014-01-01

Although laparoscopic adrenalectomy has remained the standard of care for the treatment for adrenal tumors, percutaneous image-guided ablation therapy, such as chemical ablation, radiofrequency ablation, cryoablation, and microwave ablation, has been shown to be clinically useful in many nonsurgical candidates. Ablation therapy has been used to treat both functioning adenomas and malignant tumors, including primary adrenal carcinoma and metastasis. For patients with functioning adenomas, biochemical and symptomatic improvement is achieved in 96 to 100% after ablation; for patients with malignant adrenal neoplasms, however, the survival benefit from ablation therapy remains unclear, though good initial results have been reported. This article outlines the current role of ablation therapy for adrenal lesions, as well as identifying some of the technical considerations for this procedure. PMID:25049444

Enhancing acute myeloid leukemia therapy - monitoring response using residual disease testing as a guide to therapeutic decision-making.

PubMed

Tomlinson, Benjamin; Lazarus, Hillard M

2017-06-01

Current standards for monitoring the response of acute myeloid leukemia (AML) are based on morphologic assessments of the bone marrow and recovery of peripheral blood counts. A growing experience is being developed to enhance the detection of small amounts of AML, or minimal residual disease (MRD). Areas covered: Available techniques include multi-color flow cytometry (MFC) of leukemia associated immunophenotypes (LAIP), quantitative reverse transcriptase polymerase chain reaction (QRT-PCR) for detecting fusion and mutated genes (RUNX1-RUNX1T1, CBFB-MYH11, and NPM1), overexpression of genes such as WT1, and next generation sequencing (NGS) for MRD. Expert commentary: While MRD monitoring is standard of care in some leukemia subsets such as acute promyelocytic leukemia, this approach for the broader AML population does not universally predict outcomes as some patients may experience relapse in the setting of undetectable leukemia while others show no obvious disease progression despite MRD positivity. However, there are instances where MRD can identify patients at increased risk for relapse that may change recommended therapy. Currently, prospective investigations to define clinically relevant MRD thresholds are ongoing. Risk-adapted trials are needed to best define the use of MRD in the follow up of AML patients after initial induction therapy.

3D mathematical modeling of glioblastoma suggests that transdifferentiated vascular endothelial cells mediate resistance to current standard-of-care therapy

PubMed Central

Yan, Huaming; Romero-López, Mónica; Benitez, Lesly I.; Di, Kaijun; Frieboes, Hermann B.; Hughes, Christopher C. W.; Bota, Daniela A.; Lowengrub, John S.

2017-01-01

Glioblastoma (GBM), the most aggressive brain tumor in human patients, is decidedly heterogeneous and highly vascularized. Glioma stem/initiating cells (GSC) are found to play a crucial role by increasing cancer aggressiveness and promoting resistance to therapy. Recently, crosstalk between GSC and vascular endothelial cells has been shown to significantly promote GSC self-renewal and tumor progression. Further, GSC also transdifferentiate into bona-fide vascular endothelial cells (GEC), which inherit mutations present in GSC and are resistant to traditional anti-angiogenic therapies. Here we use 3D mathematical modeling to investigate GBM progression and response to therapy. The model predicted that GSC drive invasive fingering and that GEC spontaneously form a network within the hypoxic core, consistent with published experimental findings. Standard-of-care treatments using DNA-targeted therapy (radiation/chemo) together with anti-angiogenic therapies, reduced GBM tumor size but increased invasiveness. Anti-GEC treatments blocked the GEC support of GSC and reduced tumor size but led to increased invasiveness. Anti-GSC therapies that promote differentiation or disturb the stem cell niche effectively reduced tumor invasiveness and size, but were ultimately limited in reducing tumor size because GEC maintain GSC. Our study suggests that a combinatorial regimen targeting the vasculature, GSC, and GEC, using drugs already approved by the FDA, can reduce both tumor size and invasiveness and could lead to tumor eradication. PMID:28536277

Systemic therapy in muscle-invasive and metastatic bladder cancer: current trends and future promises.

PubMed

Aragon-Ching, Jeanny B; Trump, Donald L

2016-09-01

Bladder urothelial cancers remain an important urologic cancer with limited treatment options in the locally advanced and metastatic setting. While neoadjuvant chemotherapy for locally advanced muscle-invasive cancers has shown overall survival benefit, clinical uptake in practice have lagged behind. Controversies surrounding adjuvant chemotherapy use are also ongoing. Systemic therapies for metastatic bladder cancer have largely used platinum-based therapies without effective standard second-line therapy options for those who fail, although vinflunine is approved in Europe as a second-line therapy based on a Phase III trial, and most recently, atezolizumab, a checkpoint inhibitor, was approved by the US FDA. Given increasing recognition of mutational signatures expressed in urothelial carcinomas, several promising agents with use of VEGF-targeted therapies, HER2-directed agents and immunotherapies with PD-1/PD-L1 antibodies in various settings are discussed herein.

Management strategies in pancreatic cancer.

PubMed

Campen, Christopher J; Dragovich, Tomislav; Baker, Amanda F

2011-04-01

Current first-line and adjuvant chemotherapeutic strategies for management of patients with pancreatic cancer are reviewed. Pancreatic adenocarcinoma is the 10th most prevalent cancer and the fourth most common cause of cancer deaths in the United States. More than 80% of patients with pancreatic cancer are diagnosed with locally advanced or metastatic disease and are not candidates for surgery; these patients often require multimodal treatment. The most widely used chemotherapy for such patients, as well as patients requiring adjuvant therapy after surgery, is gemcitabine or gemcitabine-based chemotherapy. All current chemotherapies for pancreatic cancer are associated with dose-limiting hematologic toxicity and other adverse effects that require ongoing monitoring and dosage adjustment to balance the benefits and risks of treatment. Pharmacists can play an important role in monitoring and providing drug information and guidance to patients and oncologists. Current investigational strategies include efforts to improve chemotherapy response rates and outcomes through modulation of cell signaling pathways and use of nanotechnology to improve drug delivery. Current management of pancreatic cancer is multifaceted, involving anticancer therapy, supportive care, and toxicity management. Standard systemic therapy with gemcitabine as a single agent or in combination with other cytotoxic agents provides modest benefits in terms of response and symptom control.

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).

Aquatic Therapy for People with Lymphedema: A Systematic Review and Meta-analysis.

PubMed

Yeung, Wai; Semciw, Adam I

2018-02-01

Aquatic therapy has several proposed benefits for people with lymphedema. A systematic review of the evidence for aquatic therapy in lymphedema management has not been conducted. Systematic review and meta-analysis were conducted. Five electronic databases were searched to identify randomized controlled trials (RCTs) of people with lymphedema, which compared aquatic therapy with other lymphedema interventions. Qualitative analysis was undertaken where quantitative analysis was not possible. Study quality was assessed using physiotherapy evidence database (PEDro) scores. The strength of evidence was evaluated using the Grades of Recommendations Assessment, Development and Evaluation (GRADE) approach. Four RCTs of moderate quality (average PEDro score 6.5/10) were included in the review. Two studies provided results for inclusion in meta-analysis. There was moderate-level evidence of no significant short-term differences in lymphedema status (as measured by lymphedema relative volume) between patients who completed aqua lymphatic therapy (ALT) compared to land-based standard care (standardized mean difference [SMD]: 0.14; 95% confidence interval [CI]: -0.37 to 0.64, I 2  = 0%, p = 0.59); and low-quality evidence of no significant difference between ALT and standard care for improving upper limb (UL) physical function (SMD -0.27, 95% CI: -0.78 to 0.23, I 2  = 0%, p = 0.29). No adverse events reported. Current evidence indicates no significant benefit of ALT over standard land-based care for improving lymphedema status or physical function in people with UL lymphedema. Patient preference should guide the choice of care to facilitate adherence. Further research is required to strengthen the evidence from four studies in people with UL lymphedema, and to establish the efficacy of this intervention in people with lower limb lymphedema. Review registration: PROSPERO (CRD42015019900).

Fast, low-dose patient localization on TomoTherapy via topogram registration.

PubMed

Moore, Kevin L; Palaniswaamy, Geethpriya; White, Benjamin; Goddu, S Murty; Low, Daniel A

2010-08-01

To investigate a protocol which efficiently localizes TomoTherapy patients with a scout imaging (topogram) mode that can be used with or instead of 3D megavoltage computed tomography (MVCT) imaging. The process presented here is twofold: (a) The acquisition of the topogram using the TomoTherapy MV imaging system and (b) the generation of a digitally reconstructed topogram (DRT) derived from a standard kV CT simulation data set. The unique geometric characteristics of the current TomoTherapy imaging system were explored both theoretically and by acquiring topograms of anthropomorphic phantoms and comparing these images to DRT images. The performance of the MV topogram imaging system in terms of image quality, dose incurred to the patient, and acquisition time was investigated using ionization chamber and radiographic film measurements. The time required to acquire a clinically usable topogram, limited by the maximum couch speed of 4.0 cm s(-1), was 12.5 s for a 50 cm long field. The patient dose was less than 1% of that delivered by a helical MVCT scan. Further refinements within the current TomoTherapy system, most notably decreasing the imaging beam repetition rate during MV topogram acquisition, would further reduce the topogram dose to less than 25 microGy per scan without compromising image quality. Topogram localization on TomoTherapy is a fast and low-dose alternative to 3D MVCT localization. A protocol designed that exclusively utilized MV topograms would result in a 30-fold reduction in imaging time and a 100-fold reduction in dose from localization scans using the current TomoTherapy workflow.

A Brief Report on the Ethical and Legal Guides For Technology Use in Marriage and Family Therapy.

PubMed

Pennington, Michael; Patton, Rikki; Ray, Amber; Katafiasz, Heather

2017-10-01

Marriage and family therapists (MFTs) use ethical codes and state licensure laws/rules as guidelines for best clinical practice. It is important that professional codes reflect the potential exponential use of technology in therapy. However, current standards regarding technology use lack clarity. To explore this gap, a summative content analysis was conducted on state licensure laws/rules and professional ethical codes to find themes and subthemes among the many aspects of therapy in which technology can be utilized. Findings from the content analysis indicated that while there have been efforts by both state and professional organizations to incorporate guidance for technology use in therapy, a clear and comprehensive "roadmap" is still missing. Future scholarship is needed that develops clearer guidelines for therapists. © 2017 American Association for Marriage and Family Therapy.

The impact of the immune system on the safety and efficiency of enzyme replacement therapy in lysosomal storage disorders.

PubMed

Broomfield, A; Jones, S A; Hughes, S M; Bigger, B W

2016-07-01

In the light of clinical experience in infantile onset Pompe patients, the immunological impact on the tolerability and long-term efficacy of enzyme replacement therapy (ERT) for lysosomal storage disorders has come under renewed scrutiny. This article details the currently proposed immunological mechanisms involved in the development of anti-drug antibodies and the current therapies used in their treatment. Given the current understanding of the adaptive immune response, it focuses particularly on T cell dependent mechanisms and the paradigm of using lymphocytic negative selection as a predictor of antibody formation. This concept originally postulated in the 1970s, stipulated that the genotypically determined lack of production or production of a variant protein determines an individual's lymphocytic repertoire. This in turn is the key factor in determining the potential severity of an individual's immunological response to ERT. It also highlights the need for immunological assay standardization particularly those looking at describing the degree of functional impact, robust biochemical or clinical endpoints and detailed patient subgroup identification if the true evaluations of impact are to be realised.

Chemotherapy and biological treatment options in breast cancer patients with brain metastasis: an update.

PubMed

Arslan, Cagatay; Dizdar, Omer; Altundag, Kadri

2014-08-01

Breast cancer (BC) is the second most common cause of CNS metastasis. Ten to 20% of all, and 38% of human epidermal growth factor-2(+), metastatic BC patients experience brain metastasis (BM). Prolonged survival with better control of systemic disease and limited penetration of drugs to CNS increased the probability of CNS metastasis as a sanctuary site of relapse. Treatment of CNS disease has become an important component of overall disease control and quality of life. Current standard therapy for BM is whole-brain radiotherapy, surgery, stereotactic body radiation therapy for selected cases, corticosteroids and systemic chemotherapy. Little progress has been made in chemotherapy for the treatment of BM in patients with BC. Nevertheless, new treatment choices have emerged. In this review, we aimed to update current and future treatment options in systemic treatment for BM of BC. Cornerstone local treatment options for BM of BC are radiotherapy and surgery in selected cases. Efficacy of cytotoxic chemotherapeutics is limited. Among targeted therapies, lapatinib has activity in systemic treatment of BM particularly when used in combination with capecitabine. Novel agents are currently investigated.

[Concomitant use of abiraterone acetate and triptorelin in patients with castration-resistant prostate cancer].

PubMed

Rapoport, L M; Bezrukov, E A; Kondrashina, A V

2016-02-01

The relevance of drug treatment for prostate cancer increases with the number of patients who develop castration resistance. Currently, no unified treatment regimen for castration-resistant prostate cancer exists, but the standard treatment for these patients is continuous androgen deprivation therapy. This paper presents the experience of concomitant use of abiraterone acetate and triptorelin in patients with castration-resistant prostate cancer. Ten patients with disease duration of 1.5 to 18 years and established castration resistance are currently being followed up. Nine of ten patients have long-term bone metastases, one patient has visceral metastases. The combination therapy produced a significant PSA decrease in nine patients and regression of bone lesions in two patients.

[Recent Advances in Immunotherapy for Non-Small Cell Lung Cancer].

PubMed

Muto, Satoshi; Suzuki, Hiroyuki

2018-02-01

Cancer immunotherapy for non-small cell lung cancer began around 1970 with nonspecific immunomodulators and cytokine therapies. This has since developed into cell therapy including lymphokine-activated killer cells(LAK)and tumor infiltrating lymphocytes(TIL), as well as cancer vaccine therapy. However, no clear indication of effectiveness has been reported. Despite the high expectation over the effectiveness of cancer vaccine therapy, the treatment strategy was deemed unsuccessful, and focus turned to the study of immune escape mechanism, which is now regarded as standard treatment for non-small cell lung cancer. With the advent of immune checkpoint inhibitors, cancer immunotherapy has finally become a standard treatment for non-small cell lung cancer. There are still several obstacles to overcome including the identification of a predictive biomarker for improved efficacy, as well as the establishment of multidrug or multimodality combination therapy. PD-L1 expression is currently used as a predictive biomarker for anti-PD-1 therapy, but does not meet the expectations of the aimed results. Although tumor mutation burden is considered another promising biomarker, there remain clinical problems, for example the need of next generation sequencer. It was reported that combination therapy of immune checkpoint inhibitor after chemoradiation therapy was also effective. However, it remains unclear of what is required to further improve the clinical effects. In this article, we will review the history of cancer immunotherapy for non-small cell lung cancer and discuss the future prospects.

Focal therapy in prostate cancer: the current situation

PubMed Central

Jácome-Pita, FX; Sánchez-Salas, R; Barret, E; Amaruch, N; Gonzalez-Enguita, C; Cathelineau, X

2014-01-01

Prostate cancer is one of the most significant pathologies in the field of urology. The adoption of screening strategies and improvements in biopsies have resulted in an increase in early-stage tumour detection. Radical global therapies provide very good oncological results in localised prostate cancer. However, excess treatment in low- and, in some cases, intermediate-risk groups affects the quality of life of these patients. In the case of localised prostate cancer, focal therapies offer a minimally invasive option with good results with respect to established treatments. Although this is currently not a standard treatment, it represents the therapeutic approach with the greatest potential. This literature review has the following objectives: to define selection criteria for patients who are candidates for focal therapy, to assess the current situation and results of the different therapeutic options, and to define procedures in cases of recurrence and for follow-ups. We concluded that focal therapy is a viable therapeutic alternative for localised prostate cancer, specifically cryosurgery and high-intensity targeted ultrasound, which have acceptable oncologic results and a lower comorbidity compared with global treatments. Studies with a high level of scientific evidence are still needed to validate these results. Acquisition of evidence A search was carried out on the Medline (PubMed), EMBASE, Web of Science and Cochrane databases of all papers published before 31 July 2013. We included clinical studies and literature reviews that evaluated primary focal therapy for prostate cancer confirmed by biopsy and excluded focal rescue therapy studies. The keywords used were focal therapy and prostate cancer. Initially, we found 42 articles; 15 studies were excluded because they did not meet the minimum criteria for inclusion. A total of 1350 cases were treated throughout 27 studies. PMID:24944577

Sarcoidosis: an update on current pharmacotherapy options and future directions.

PubMed

Brito-Zerón, Pilar; Pérez-Alvarez, Roberto; Pallarés, Lucio; Retamozo, Soledad; Baughman, Robert P; Ramos-Casals, Manuel

2016-12-01

Sarcoidosis is a systemic disease of unknown etiology characterized by the development of non-caseating epitheloid granulomas. The lungs are the most commonly involved organ (>90% of cases), followed by the lymph nodes, the skin, and the eyes. Areas covered: This review summarizes current pharmacotherapy options and future directions for the development of new therapies. Glucocorticoids are the first-line therapy for sarcoidosis. For patients with the most severe forms of sarcoidosis (who will need glucocorticoids for long periods) and for those intolerant or refractory, immunosuppressive drugs are used as sparing agents. The management of extrathoracic sarcoidosis must be tailored to the specific organ or organs involved; however, there is limited data from controlled trials to guide the treatment of these patients. The emergence of biological therapies has increased the therapeutic armamentarium available to treat sarcoidosis, with monoclonal anti-TNF agents being the most promising, but their use is still limited by a lack of licensing and costs. Expert commentary: The treatment of sarcoidosis is still not totally standardized. New effective therapies are urgently needed to enable the reduction or replacement of long-term therapy with glucocorticoids in patients with sarcoidosis.

The Selective Use of Radiation Therapy in Rectal Cancer Patients.

PubMed

Martella, Andrew; Willett, Christopher; Palta, Manisha; Czito, Brian

2018-04-11

Colorectal cancer has a high global incidence, and standard treatment employs a multimodality approach. In addition to cure, minimizing treatment-related toxicity and improving the therapeutic ratio is a common goal. The following article addresses the potential of omitting radiotherapy in select rectal cancer patients. Omission of radiotherapy in rectal cancer is analyzed in the context of historical findings, as well as more recent data describing risk stratification of stage II-III disease, surgical optimization, imaging limitations, improvement in systemic chemotherapeutic agents, and contemporary studies evaluating selective omission of radiotherapy. A subset of rectal cancer patients exists that may be considered low to intermediate risk for locoregional recurrence. With appropriate staging, surgical technique, and possibly improved systemic therapy, it may be feasible to selectively omit radiotherapy in these patients. Current imaging limitations as well as evidence of increased locoregional recurrence following radiotherapy omission lend us to continue supporting the standard treatment of approach of neoadjuvant chemoradiation therapy followed by surgical resection until additional improvements and prospective evidence can support otherwise.

State of the art: nursing knowledge and electroconvulsive therapy.

PubMed

Froimson, L; Creed, P; Mathew, L

1995-09-01

Nursing services attempting to develop standards for their own facilities will find limited literature specific to nursing and electroconvulsive therapy (ECT) in American publications. From 1966 to December 1994, there were only 19 publications in American nursing journals that provide a specific focus on nursing and ECT. Only one of these articles reported research findings. Twenty-seven citations in Convulsive Therapy included nurse contributors. While the APA Task Force on the Practice of ECT has addressed educational needs of nursing and technical elements of the procedure, there do not currently exist specific standards for nursing practice in ECT. Concerns salient to nursing that have generated articles by nurses include instruction of patients, support to patients and families, safety of patients, assessment of clinical status, informed consent, and nurses' and patients' attitudes about ECT. Nurses are encouraged to join their physician-colleagues in developing and disseminating the information needed for the field of nursing to contribute its own expertise to the care of patients receiving ECT.

CAR T-Cell Therapies in Glioblastoma: A First Look.

PubMed

Migliorini, Denis; Dietrich, Pierre-Yves; Stupp, Roger; Linette, Gerald P; Posey, Avery D; June, Carl H

2018-02-01

Glioblastoma is an aggressive malignancy with a poor prognosis. The current standard of care for newly diagnosed glioblastoma patients includes surgery to the extent, temozolomide combined with radiotherapy, and alternating electric fields therapy. After recurrence, there is no standard therapy and survival is less than 9 months. Recurrent glioblastoma offers a unique opportunity to investigate new treatment approaches in a malignancy known for remarkable genetic heterogeneity, an immunosuppressive microenvironment, and a partially permissive anatomic blood-brain barrier. Results from three first-in-man chimeric antigen receptor (CAR) T-cell trials targeting IL13Rα2, Her2/CMV, and EGFRvIII have recently been reported. Each one of these trials addresses important questions, such as T-cell trafficking to CNS, engraftment and persistence, tumor microenvironment remodeling, and monitoring of glioma response to CAR T cells. Objective radiologic responses have been reported. Here, we discuss and summarize the results of these trials and suggest opportunities for the field. Clin Cancer Res; 24(3); 535-40. ©2017 AACR . ©2017 American Association for Cancer Research.

Liquid biopsies in gastrointestinal malignancies: when is the big day?

PubMed

Lopez, Anthony; Harada, Kazuto; Mizrak Kaya, Dilsa; Dong, Xiaochuan; Song, Shumei; Ajani, Jaffer A

2018-01-01

Tumor tissue sample is currently the gold standard for diagnosing gastrointestinal cancers, but also for genomic/immune component analyses that can help in the selection of therapy. However, this approach of studying a 'representative' sample of the tumor does not address inherent heterogeneity. Liquid biopsies, mainly represented by circulating tumor cells, circulating tumor DNA, tumor exosomes, and microRNAs, have the potential to assess various biomarkers for early detection of cancer, carrying out genomic/immune profiling for not only selection of appropriate therapy but also to monitor effect of therapy. Areas covered: This review summarizes the current evidence in the literature on liquid biopsies in gastrointestinal cancers concerning diagnosis, prognosis, and response to therapy. The following terms were used in PubMed: 'esophageal', 'gastric', 'colorectal', 'cancer', 'circulating tumor cells', 'circulating tumor DNA', microRNA', 'diagnosis', 'prognosis', 'response', 'resistance'. Expert commentary: Data increasingly supports the potential of liquid biopsies for early detection, selection of therapy, and monitoring response to therapy. One major question is whether assaying various components of the blood would accommodate considerable context-dependent heterogeneity of gastrointestinal tumors. There are many potential strategies to exploit liquid biopsy use. To put them in to perspective, well-designed and meticulous prospective studies will be needed to prove their usefulness.

Neonatal and pediatric extracorporeal membrane oxygenation in developing Latin American countries.

PubMed

Kattan, Javier; González, Álvaro; Castillo, Andrés; Caneo, Luiz Fernando

To review the principles of neonatal-pediatric extracorporeal membrane oxygenation therapy, prognosis, and its establishment in limited resource-limited countries in Latino America. The PubMed database was explored from 1985 up to the present, selecting from highly-indexed and leading Latin American journals, and Extracorporeal Life Support Organization reports. Extracorporeal membrane oxygenation provides "time" for pulmonary and cardiac rest and for recovery. It is used in the neonatal-pediatric field as a rescue therapy for more than 1300 patients with respiratory failure and around 1000 patients with cardiac diseases per year. The best results in short- and long-term survival are among patients with isolated respiratory diseases, currently established as a standard therapy in referral centers for high-risk patients. The first neonatal/pediatric extracorporeal membrane oxygenation Program in Latin America was established in Chile in 2003, which was also the first program in Latin America to affiliate with the Extracorporeal Life Support Organization. New extracorporeal membrane oxygenation programs have been developed in recent years in referral centers in Argentina, Colombia, Brazil, Mexico, Perú, Costa Rica, and Chile, which are currently funding the Latin American Extracorporeal Life Support Organization chapter. The best results in short- and long-term survival are in patients with isolated respiratory diseases. Today extracorporeal membrane oxygenation therapy is a standard therapy in some Latin American referral centers. It is hoped that these new extracorporeal membrane oxygenation centers will have a positive impact on the survival of newborns and children with respiratory or cardiac failure, and that they will be available for an increasing number of patients from this region in the near future. Copyright © 2016 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

Advances and unmet needs in genetic, basic and clinical science in Alport syndrome: report from the 2015 International Workshop on Alport Syndrome

PubMed Central

Gross, Oliver; Kashtan, Clifford E.; Rheault, Michelle N.; Flinter, Frances; Savige, Judith; Miner, Jeffrey H.; Torra, Roser; Ars, Elisabet; Deltas, Constantinos; Savva, Isavella; Perin, Laura; Renieri, Alessandra; Ariani, Francesca; Mari, Francesca; Baigent, Colin; Judge, Parminder; Knebelman, Bertrand; Heidet, Laurence; Lagas, Sharon; Blatt, Dave; Ding, Jie; Zhang, Yanqin; Gale, Daniel P.; Prunotto, Marco; Xue, Yong; Schachter, Asher D.; Morton, Lori C.G.; Blem, Jacqui; Huang, Michael; Liu, Shiguang; Vallee, Sebastien; Renault, Daniel; Schifter, Julia; Skelding, Jules; Gear, Susie; Friede, Tim; Turner, A. Neil; Lennon, Rachel

2017-01-01

Abstract Alport syndrome (AS) is a genetic disease characterized by haematuric glomerulopathy variably associated with hearing loss and anterior lenticonus. It is caused by mutations in the COL4A3, COL4A4 or COL4A5 genes encoding the α3α4α5(IV) collagen heterotrimer. AS is rare, but it accounts for >1% of patients receiving renal replacement therapy. Angiotensin-converting enzyme inhibition slows, but does not stop, the progression to renal failure; therefore, there is an urgent requirement to expand and intensify research towards discovering new therapeutic targets and new therapies. The 2015 International Workshop on Alport Syndrome targeted unmet needs in basic science, genetics and diagnosis, clinical research and current clinical care. In three intensive days, more than 100 international experts including physicians, geneticists, researchers from academia and industry, and patient representatives from all over the world participated in panel discussions and breakout groups. This report summarizes the most important priority areas including (i) understanding the crucial role of podocyte protection and regeneration, (ii) targeting mutations by new molecular techniques for new animal models and potential gene therapy, (iii) creating optimal interaction between nephrologists and geneticists for early diagnosis, (iv) establishing standards for mutation screening and databases, (v) improving widespread accessibility to current standards of clinical care, (vi) improving collaboration with the pharmaceutical/biotech industry to investigate new therapies, (vii) research in hearing loss as a huge unmet need in Alport patients and (viii) the need to evaluate the risk and benefit of novel (including ‘repurposing’) therapies on an international basis. PMID:27190345

Advances and unmet needs in genetic, basic and clinical science in Alport syndrome: report from the 2015 International Workshop on Alport Syndrome.

PubMed

Gross, Oliver; Kashtan, Clifford E; Rheault, Michelle N; Flinter, Frances; Savige, Judith; Miner, Jeffrey H; Torra, Roser; Ars, Elisabet; Deltas, Constantinos; Savva, Isavella; Perin, Laura; Renieri, Alessandra; Ariani, Francesca; Mari, Francesca; Baigent, Colin; Judge, Parminder; Knebelman, Bertrand; Heidet, Laurence; Lagas, Sharon; Blatt, Dave; Ding, Jie; Zhang, Yanqin; Gale, Daniel P; Prunotto, Marco; Xue, Yong; Schachter, Asher D; Morton, Lori C G; Blem, Jacqui; Huang, Michael; Liu, Shiguang; Vallee, Sebastien; Renault, Daniel; Schifter, Julia; Skelding, Jules; Gear, Susie; Friede, Tim; Turner, A Neil; Lennon, Rachel

2017-06-01

Alport syndrome (AS) is a genetic disease characterized by haematuric glomerulopathy variably associated with hearing loss and anterior lenticonus. It is caused by mutations in the COL4A3, COL4A4 or COL4A5 genes encoding the α3α4α5(IV) collagen heterotrimer. AS is rare, but it accounts for >1% of patients receiving renal replacement therapy. Angiotensin-converting enzyme inhibition slows, but does not stop, the progression to renal failure; therefore, there is an urgent requirement to expand and intensify research towards discovering new therapeutic targets and new therapies. The 2015 International Workshop on Alport Syndrome targeted unmet needs in basic science, genetics and diagnosis, clinical research and current clinical care. In three intensive days, more than 100 international experts including physicians, geneticists, researchers from academia and industry, and patient representatives from all over the world participated in panel discussions and breakout groups. This report summarizes the most important priority areas including (i) understanding the crucial role of podocyte protection and regeneration, (ii) targeting mutations by new molecular techniques for new animal models and potential gene therapy, (iii) creating optimal interaction between nephrologists and geneticists for early diagnosis, (iv) establishing standards for mutation screening and databases, (v) improving widespread accessibility to current standards of clinical care, (vi) improving collaboration with the pharmaceutical/biotech industry to investigate new therapies, (vii) research in hearing loss as a huge unmet need in Alport patients and (viii) the need to evaluate the risk and benefit of novel (including 'repurposing') therapies on an international basis. © The Author 2016. Published by Oxford University Press on behalf of ERAEDTA.

Induction chemotherapy vs post-operative adjuvant therapy for malignant pleural mesothelioma.

PubMed

Marulli, Giuseppe; Faccioli, Eleonora; Bellini, Alice; Mammana, Marco; Rea, Federico

2017-08-01

Malignant pleural mesothelioma (MPM) is an aggressive neoplasia. Multidisciplinary treatments, including the association of induction and/or adjuvant therapeutic regimens with surgery, have been reported to give encouraging results. Current therapeutic options are not well standardized yet, especially regarding the best association between surgery and medical treatments. The present review aims to assess safety, efficacy and outcomes of different therapies for MPM. Areas covered: This article focuses on the multimodality treatment of mesothelioma. A systematic review was performed by using electronic databases to identify studies that considered induction and adjuvant approaches in MPM therapy in a multidisciplinary setting, including surgery. Endpoints included overall survival, disease free survival, disease recurrence, and complications. Expert commentary: This systematic review offers a comprehensive view of current multidisciplinary therapeutic strategies for MPM, suggesting that multimodality therapy offers acceptable outcomes with better results reported for trimodality approaches. Individualization of care for each patient is fundamental in choosing the most appropriate treatment. The growing complexity of treatment protocols mandates that MPM patients be referred to specialized Centers, in which every component of the interdisciplinary team can provide the necessary expertise and quality of care.

Triple therapy in chronic hepatitis C: initial series in a public health program in the South of Brazil.

PubMed

Almeida, Paulo R L; Fonseca, Carla Bortolin; Koch, Vivian W; Souza, Amanda M; Feltrin, Alberi A; Tovo, Cristiane Valle

2015-01-01

Chronic hepatitis C has great impact on world's health. Current therapy for genotype 1 hepatitis C virus includes protease inhibitors boceprevir and telaprevir, associated to standard therapy - peginterferon alfa + ribavirin. There are no published data in Brazil on the results of this new therapy, and it is interesting an evaluation of what was accomplished up to this moment. Objectives To evaluate virologic response to triple therapy, as well as the safety profile and tolerability. This study is a clinical series of patients receiving triple therapy for C hepatitis in a single center of a Public Health System of South Brasil. Out of the 121 patients that initiated the triple therapy, the first patients that finished the treatment and evaluated the sustained virological response (24 weeks after the end of treatment) were included. Twenty four genotype 1 chronic hepatitis C monoinfected patients were included. Nineteen (79.2%) patients had been previously treated. Thirteen (54.2%) patients were cirrhotic. Nineteen (79.2%) patients completed the planned therapy. By the end of the treatment, 14 (58.3%) out of 24 patients had undetectable viral load. Sustained virologic response occurred in 12 (50.0%) out of 24 patients, 07 (58.3%) in telaprevir group and 05 (41.7%) in boceprevir group. Out of 24 patients under triple therapy, 58% (n=14) presented anemia. In conclusion, despite the small number of patients treated with triple therapy evaluated in the current study, it possibly reflects the population under this therapy in real-life.

The role of targeted therapy in the management of patients with AML

PubMed Central

2017-01-01

Drug therapy for acute myeloid leukemia (AML) is finally undergoing major changes in 2017. This is due to the US Food and Drug Administration’s approval of several new, targeted agents (midostaurin, enasidenib, and gemtuzumab ozogamicin). Paired with the recent approval of a novel liposomal formulation of daunorubicin/cytarabine (CPX-351/Vyxeos), the standard of care is changing rapidly in AML for subgroups. This review will focus on currently approved agents and promising novel agents in development and will highlight controversial areas in targeted treatment. PMID:29296877

The role of targeted therapy in the management of patients with AML.

PubMed

Perl, Alexander E

2017-11-14

Drug therapy for acute myeloid leukemia (AML) is finally undergoing major changes in 2017. This is due to the US Food and Drug Administration's approval of several new, targeted agents (midostaurin, enasidenib, and gemtuzumab ozogamicin). Paired with the recent approval of a novel liposomal formulation of daunorubicin/cytarabine (CPX-351/Vyxeos), the standard of care is changing rapidly in AML for subgroups. This review will focus on currently approved agents and promising novel agents in development and will highlight controversial areas in targeted treatment.

Floating Gate sensor for in-vivo dosimetry in radiation therapies. Design and first characterization.

NASA Astrophysics Data System (ADS)

Faigon, A.; Martinez Vazquez, I.; Carbonetto, S.; García Inza, M.; G

2017-01-01

A floating gate dosimeter was designed and fabricated in a standard CMOS technology. The design guides and characterization are presented. The characterization included the controlled charging by tunneling of the floating gate, and its discharging under irradiation while measuring the transistor drain current whose change is the measure of the absorbed dose. The resolution of the obtained device is close to 1 cGy satisfying the requirements for most radiation therapies dosimetry. Pending statistical proofs, the dosimeter is a potential candidate for wide in-vivo control of radiotherapy treatments.

Prevention of bacterial infection in pediatric oncology: what do we know, what can we learn?

PubMed

Alexander, Sarah; Nieder, Michael; Zerr, Danielle M; Fisher, Brian T; Dvorak, Christopher C; Sung, Lillian

2012-07-15

Bacterial sepsis continues to be a leading cause of morbidity and toxic death in children receiving intensive therapy for cancer. Empiric therapy for suspected infections and treatment of documented infections are well-established standards of care. The routine use of prophylactic strategies is much less common in pediatric oncology. This paper will review the current literature on the use and risks of antimicrobial prophylaxis as well as non-pharmacological methods for infection prevention and will address areas in need of further research. Copyright © 2011 Wiley Periodicals, Inc.

[Progress of treatments in non-small cell lung cancer with brain metastases].

PubMed

Ma, Chunhua; Jiang, Rong

2012-05-01

Brain metastases is one of the most common complications of non-small cell lung cancer, whole brain radiotherapy (WBRT), stereotactic radiosurgery (SRS), surgery and chemotherapy are standard methods in the treatment of brain metastases. But the effect of those treatments are still sad. Comprehensive treatment can prolong the survival and improve the quality of life. Recently, the improvement of technology, targeted therapy, survival time and the quality of life are in increasingly concerned. The paper make a summary of current situation and progress for comprehensive therapy of brain metastases.

Management strategies for persistent epithelial defects of the cornea

PubMed Central

Katzman, Lee R.; Jeng, Bennie H.

2014-01-01

Management of patients with persistent epithelial defects of the cornea can be challenging to even the seasoned ophthalmologist. It is essential that one understands not only the pathophysiology of the failure of the epithelium to migrate and close a wound appropriately, but also the mechanism of action of the available treatment modalities at one’s disposal. This article serves as a review of current standard therapies, recently introduced alternative therapies gaining in popularity, and a look into the newest developments that may change the way we manage corneal surface disease. PMID:25278792

Current concepts of severe asthma

PubMed Central

Raundhal, Mahesh; Oriss, Timothy B.; Ray, Prabir; Wenzel, Sally E.

2016-01-01

The term asthma encompasses a disease spectrum with mild to very severe disease phenotypes whose traditional common characteristic is reversible airflow limitation. Unlike milder disease, severe asthma is poorly controlled by the current standard of care. Ongoing studies using advanced molecular and immunological tools along with improved clinical classification show that severe asthma does not identify a specific patient phenotype, but rather includes patients with constant medical needs, whose pathobiologic and clinical characteristics vary widely. Accordingly, in recent clinical trials, therapies guided by specific patient characteristics have had better outcomes than previous therapies directed to any subject with a diagnosis of severe asthma. However, there are still significant gaps in our understanding of the full scope of this disease that hinder the development of effective treatments for all severe asthmatics. In this Review, we discuss our current state of knowledge regarding severe asthma, highlighting different molecular and immunological pathways that can be targeted for future therapeutic development. PMID:27367183

Global risk management in type 2 diabetes: blood glucose, blood pressure, and lipids--update on the background of the current guidelines.

PubMed

Clemens, A; Siegel, E; Gallwitz, B

2004-10-01

Diabetes mellitus presents a significant public health burden based on its increased morbidity, mortality, and economic cost. The high comorbidity and prevalence of concomitant diseases like hypertension and dyslipidemia in diabetic patients cause the high risk in developing secondary, cost intensive, and for the patient often disastrous late complications (nephropathy, retinopathy, neuropathy, and cardiovascular disease). Therefore, patients with diabetes mellitus need a global risk management that takes the various individual clinical problems into account. The current global standards of therapy in patients with diabetes mellitus are focused on the control of glycemia, blood pressure, and lipid levels, as well as aspirin therapy and avoiding of smoking. There are a number of guidelines and recommendations to manage these global issues. Our review will summarize current recommendations and consolidate therapeutic goals and treatments that are of vital importance in the global risk management in diabetic patients.

The Quest for an Effective Treatment for an Intractable Cancer: Established and Novel Therapies for Pancreatic Adenocarcinoma.

PubMed

Quinn, Bridget A; Lee, Nathaniel A; Kegelman, Timothy P; Bhoopathi, Praveen; Emdad, Luni; Das, Swadesh K; Pellecchia, Maurizio; Sarkar, Devanand; Fisher, Paul B

2015-01-01

With therapies that date back to the 1950s, and few newly approved treatments in the last 20 years, pancreatic cancer remains a significant challenge for the development of novel therapeutics. Current regimens have successfully extended patient survival, although they still lead to prognoses measured in months rather than years. The genetic diversity inherent in pancreatic tumors forms the roadblocks that must be overcome in future therapeutics. Recent insight into the genetic patterns found in tumor cells may provide clues leading to better understanding of the challenges hindering the development of treatments. Here, we review currently used drugs and established combination therapies that comprise the standard of care for a highly recalcitrant disease. Novel approaches can improve upon current therapies in a variety of ways. Enhancing specificity, such that growth inhibition and cytotoxic effects act preferentially on tumor cells, is one approach to advance treatments. This can be accomplished through the targeting of extracellular markers specific to cancer cells. Additionally, enlisting natural defenses and overcoming tumor-driven immune suppression could prove to be a useful tactic. Recent studies utilizing these approaches have yielded promising results and could contribute to an ongoing effort battling a particularly difficult cancer. © 2015 Elsevier Inc. All rights reserved.

Recent advances in multidisciplinary management of hepatocellular carcinoma

PubMed Central

Gomaa, Asmaa I; Waked, Imam

2015-01-01

The incidence of hepatocellular carcinoma (HCC) is increasing, and it is currently the second leading cause of cancer-related death worldwide. Potentially curative treatment options for HCC include resection, transplantation, and percutaneous ablation, whereas palliative treatments include trans-arterial chemoembolization (TACE), radioembolization, and systemic treatments. Due to the diversity of available treatment options and patients’ presentations, a multidisciplinary team should decide clinical management of HCC, according to tumor characteristics and stage of liver disease. Potentially curative treatments are suitable for very-early- and early-stage HCC. However, the vast majority of HCC patients are diagnosed in later stages, where the tumor characteristics or progress of liver disease prevent curative interventions. For patients with intermediate-stage HCC, TACE and radioembolization improve survival and are being evaluated in addition to potentially curative therapies or with systemic targeted therapy. There is currently no effective systemic chemotherapy, immunologic, or hormonal therapy for HCC, and sorafenib is the only approved molecular-targeted treatment for advanced HCC. Other targeted agents are under investigation; trials comparing new agents in combination with sorafenib are ongoing. Combinations of systemic targeted therapies with local treatments are being evaluated for further improvements in HCC patient outcomes. This article provides an updated and comprehensive overview of the current standards and trends in the treatment of HCC. PMID:25866604

Dance/movement therapy for improving psychological and physical outcomes in cancer patients.

PubMed

Bradt, Joke; Shim, Minjung; Goodill, Sherry W

2015-01-07

Current cancer care increasingly incorporates psychosocial interventions. Cancer patients use dance/movement therapy to learn to accept and reconnect with their bodies, build new self-confidence, enhance self-expression, address feelings of isolation, depression, anger and fear and to strengthen personal resources. To update the previously published review that examined the effects of dance/movement therapy and standard care versus standard care alone or standard care and other interventions on psychological and physical outcomes in patients with cancer. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2014, Issue 6), MEDLINE (OvidSP, 1950 to June week 4, 2014), EMBASE (OvidSP, 1980 to 2014 week 26), CINAHL (EBSCOhost, 1982 to July 15 2014), PsycINFO (EBSCOhost, 1806 to July 15 2014), LILACS (Virual Health Library, 1982 to July 15 2014), Science Citation Index (ISI, 1974 to July 15 2014), CancerLit (1983 to 2003), International Bibliography of Theatre and Dance (1989 to July 15 2014), the National Research Register (2000 to September 2007), Proquest Digital Dissertations, ClinicalTrials.gov, and Current Controlled Trials (all to July 15 2014). We handsearched dance/movement therapy and related topics journals, reviewed reference lists and contacted experts. There was no language restriction. We included all randomized and quasi-randomized controlled trials of dance/movement therapy interventions for improving psychological and physical outcomes in patients with cancer. We considered studies only if dance/movement therapy was provided by a formally trained dance/movement therapist or by trainees in a formal dance/movement therapy program. Two review authors independently extracted the data and assessed the methodological quality, seeking additional information from the trial researchers when necessary. Results were presented using standardized mean differences. We identified one new trial for inclusion in this update. In total, the evidence for this review rests on three studies with a total of 207 participants.We found no evidence for an effect of dance/movement therapy on depression (standardized mean difference (SMD) = 0.02, 95% confidence interval (CI) -0.28 to 0.32, P = 0.89, I2 = 0%) (two studies, N = 170), stress (SMD = -0.18, 95% CI -0.48 to 0.12, P = 0.24, I2 = 0%) (two studies, N = 170), anxiety (SMD = 0.21, 95% CI -0.09 to 0.51 P = 0.18, I2 = 0%) (two studies, N = 170), fatigue (SMD = -0.36, 95% -1.26 to 0.55, P = 0.44, I² = 80%) (two studies, N = 170) and body image (SMD = -0.13, 95% CI -0.61 to 0.34, P = 0.58, I2 = 0%) (two studies, N = 68) in women with breast cancer. The data of one study with moderate risk of bias suggested that dance/movement therapy had a large beneficial effect on 37 participants' quality of life (QoL) (SMD = 0.89, 95% CI 0.21 to 1.57). One study with a high risk of bias reported greater improvements in vigor and greater reduction in somatization in the dance/movement therapy group compared to a standard care control group (N = 31). The individual studies did not find support for an effect of dance/movement therapy on mood, mental health, and pain. It is unclear whether this was due to ineffectiveness of the treatment, inappropriate outcome measures or limited power of the trials. Finally, the results of one study did not find evidence for an effect of dance/movement therapy on shoulder range of motion (ROM) or arm circumference in 37 women who underwent a lumpectomy or breast surgery. However, this was likely due to large within-group variability for shoulder ROM and a limited number of participants with lymphedema.Two studies presented moderate risk of bias and one study high risk of bias. Therefore, overall, the quality of the evidence is very low. We did not find support for an effect of dance/movement therapy on depression, stress, anxiety, fatigue and body image . The findings of individual studies suggest that dance/movement therapy may have a beneficial effect on QoL, somatization, and vigor. However, the limited number of studies prevents us from drawing conclusions concerning the effects of dance/movement therapy on psychological and physical outcomes in cancer patients.

Pragmatic Language Impairment: Case Studies of Social and Pragmatic Language Therapy

ERIC Educational Resources Information Center

Adams, Catherine; Baxendale, Janet; Lloyd, Julian; Aldred, Catherine

2005-01-01

The current position on speech and language intervention for children who have pragmatic language impairment (PLI) is limited by a lack of evidence to support practice. Two intervention outcome case studies of children with PLI, aimed at establishing efficacy, are presented in this paper. Standardized language tests and conversational sampling…

Chemotherapy and target therapy in the management of adult high- grade gliomas.

PubMed

Spinelli, Gian Paolo; Miele, Evelina; Lo Russo, Giuseppe; Miscusi, Massimo; Codacci-Pisanelli, Giovanni; Petrozza, Vincenzo; Papa, Anselmo; Frati, Luigi; Della Rocca, Carlo; Gulino, Alberto; Tomao, Silverio

2012-10-01

Adult high grade gliomas (HGG) are the most frequent and fatal primary central nervous system (CNS) tumors. Despite recent advances in the knowledge of the pathology and the molecular features of this neoplasm, its prognosis remains poor. In the last years temozolomide (TMZ) has dramatically changed the life expectancy of these patients: the association of this drug with radiotherapy (RT), followed by TMZ alone, is the current standard of care. However, malignant gliomas often remain resistant to chemotherapy (CHT). Therefore, preclinical and clinical research efforts have been directed on identifying and understanding the different mechanisms of chemo-resistance operating in this subset of tumors,in order to develop effective strategies to overcome resistance. Moreover, the evidence of alterations in signal transduction pathways underlying tumor progression, has increased the number of trials investigating molecular target agents, such as anti-epidermal growth factor receptor (EGFR) and anti- vascular endothelial growth factor (VEGF) signaling. The purpose of this review is to point out the current standard of treatment and to explore new available target therapies in HGG.

Plasma noncholesterol sterols: current uses, potential and need for standardization.

PubMed

Mackay, Dylan S; Jones, Peter J H

2012-06-01

Noncholesterol sterols (NCSs) in plasma encompass endogenous cholesterol precursors and exogenous phytosterols and cholesterol metabolites, which are used as surrogate measures of cholesterol synthesis and cholesterol absorption, respectively. The ratios of cholesterol synthesis to cholesterol absorption surrogates are also utilized to assess the overall balance of cholesterol metabolism, with higher values representing more synthesis and lower values more absorption. The objective of this review is to focus on recent findings using plasma NCSs and their potential in customizing dietary and pharmacological hypolipidemic therapies. NCSs are often used to assess the impact of pharmacological and dietary interventions on cholesterol metabolism. Various forms of dyslipidemia have been characterized using NCSs, and NCSs may be a valuable tool in selecting appropriate treatment therapies. NCSs levels are affected by genetic, dietary and physiological factors and have been related to cardiovascular disease risk. The expanded use of plasma NCSs is currently limited by the lack of standardized methodology. However, noncholesterol sterols are still a valuable research tool for the overall assessment of cholesterol metabolism and may have clinical potential in the personalization of diet and medicine.

Role of ivabradine and heart rate lowering in chronic heart failure: guideline update.

PubMed

Chow, Sheryl L; Page, Robert Lee; Depre, Christophe

2018-06-14

This review summarizes the current management of heart failure (HF) in patients with reduced ejection fraction and the potential role of heart rate lowering agents in select populations, as recommended in the updated guidelines. Areas covered: PubMed was searched for studies that evaluated the role of heart rate lowering or ivabradine in HF management. Expert commentary: Targeting heart rate may offer benefit when added to renin-angiotensin aldosterone antagonists, and beta-blockers. Ivabradine is a heart rate lowering agent that acts on the funny current (I f ) in the sinoatrial node, thereby reducing heart rate without directly affecting cardiac contraction and relaxation. Clinical data from a phase 3 trial demonstrated that ivabradine reduced the composite endpoint of cardiovascular death or hospital admission for worsening systolic HF, while maintaining an acceptable safety profile in patients receiving standard of care therapy. These data, in addition to more recently published guidelines, suggest ivabradine as a promising new treatment option for lowering heart rate after optimizing standard therapy in select patients with chronic HF.

Pain and pain management in dermatology.

PubMed

Beiteke, Ulrike; Bigge, Stefan; Reichenberger, Christina; Gralow, Ingrid

2015-10-01

It is estimated that 23 million Germans suffer from chronic pain. A recent survey has revealed that 30 % of chronic pain patients are dissatisfied with their pain management. Furthermore, five million Germans suffer from neuropathic pain, 20 % of whom are inadequately treated. Pain is also a symptom of many dermatologic diseases, which is mostly somatic and may be classified as mild in the majority of cases. Nevertheless, research on the quality of life (QoL) has increasingly shown a marked impairment of QoL by moderate pain such as in psoriatic arthritis. -Severe pain is associated with herpes zoster (shingles), leg ulcers, and pyoderma gangrenosum. This article addresses the basics of pain classification and, in a short excerpt, pain transduction/transmission and modulation. The use of standardized diagnostic -scales is recommended for the purpose of recording and monitoring pain intensity, which allows for the optimization of therapy and consistent interdisciplinary -communication. Any dermatology residency program includes the acquisition of knowledge and skills in pain management. This review therefore aims to present fundamental therapeutic concepts based on the expanded WHO analgesic ladder, and describes a step-wise therapeutic approach and combination therapies. The article focuses on the pain management of the above-mentioned severely painful, conservatively treated dermatoses. Besides well-established therapeutic agents and current -therapeutic standards, it discusses specific options based on guidelines (where available). Current knowledge on peri- and postoperative pain management is briefly outlined. This article addresses: ▸ The fundamentals of the classification and neurophysiology of pain; ▸ Standards for pain documentation in children and adults; ▸ General standards for pharmaceutical pain management; ▸ Current specific treatment options for postherpetic neuralgia, leg ulcers, and -pyoderma gangrenosum in conjunction with the expanded WHO analgesic -ladder. © 2015 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.

Human cord blood applications in cell therapy: looking back and look ahead.

PubMed

Zhou, Hongyan; Chang, Stephen; Rao, Mahendra

2012-08-01

Human umbilical cord blood (UCB) has been used as a reliable source of stem cells for blood-borne diseases and disorders. Recent advances in cell reprogramming technology to produce induced pluripotent stem (iPS) cells, which can be differentiated to multiple adult cell types, has further expanded the potential of cord blood cell therapy for treatment of non-blood-borne diseases. However, in order to harness this breakthrough technology and to provide clinical-grade cells for the patient, standardization of iPS production and differentiation, and good manufacturing practice (GMP) need to be employed. UCB is an ethical source of stem cells and has been used to treat diseases including leukemia, cancer and blood disorders. The development of iPS cell technology could potentially greatly increase the application of cord blood cells as a treatment for a broader range of diseases, UCB-iPS banks could, therefore, be a valuable complementary source of clinical-grade cells for cell therapy. The current applicability of GMP to UCB and UCB-iPS cell-based cell therapy will be discussed. Although cord blood stem cell therapies have been practiced for decades, UCB-iPS cell therapies are a new innovation currently in development. Successful clinical applications of such novel cell therapies will depend on the production of GMP-compliant cells and the establishment of cell banks.

CAMERA2 - combination antibiotic therapy for methicillin-resistant Staphylococcus aureus infection: study protocol for a randomised controlled trial.

PubMed

Tong, Steven Y C; Nelson, Jane; Paterson, David L; Fowler, Vance G; Howden, Benjamin P; Cheng, Allen C; Chatfield, Mark; Lipman, Jeffrey; Van Hal, Sebastian; O'Sullivan, Matthew; Robinson, James O; Yahav, Dafna; Lye, David; Davis, Joshua S

2016-03-31

Methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia is a serious infection resulting in 20-50 % 90-day mortality. The limitations of vancomycin, the current standard therapy for MRSA, make treatment difficult. The only other approved drug for treatment of MRSA bacteraemia, daptomycin, has not been shown to be superior to vancomycin. Surprisingly, there has been consistent in-vitro and in-vivo laboratory data demonstrating synergy between vancomycin or daptomycin and an anti-staphylococcal β-lactam antibiotic. There is also growing clinical data to support such combinations, including a recent pilot randomised controlled trial (RCT) that demonstrated a trend towards a reduction in the duration of bacteraemia in patients treated with vancomycin plus flucloxacillin compared to vancomycin alone. Our aim is to determine whether the addition of an anti-staphylococcal penicillin to standard therapy results in improved clinical outcomes in MRSA bacteraemia. We will perform an open-label, parallel-group, randomised (1:1) controlled trial at 29 sites in Australia, New Zealand, Singapore, and Israel. Adults (aged 18 years or older) with MRSA grown from at least one blood culture and able to be randomised within 72 hours of the index blood culture collection will be eligible for inclusion. Participants will be randomised to vancomycin or daptomycin (standard therapy) given intravenously or to standard therapy plus 7 days of an anti-staphylococcal β-lactam (flucloxacillin, cloxacillin, or cefazolin). The primary endpoint will be a composite outcome at 90 days of (1) all-cause mortality, (2) persistent bacteraemia at day 5 or beyond, (3) microbiological relapse, or (4) microbiological treatment failure. The recruitment target of 440 patients is based on an expected failure rate for the primary outcome of 30 % in the control arm and the ability to detect a clinically meaningful absolute decrease of 12.5 %, with a two-sided alpha of 0.05, a power of 80 %, and assuming 10 % of patients will not be evaluable for the primary endpoint. Key potential advantages of adding anti-staphylococcal β-lactams to standard therapy for MRSA bacteraemia include their safety profile, low cost, and wide availability. ClinicalTrials.gov Identifier: NCT02365493 . Registered 24 February 2015.

The role of metabolic therapy in treating glioblastoma multiforme

PubMed Central

Maroon, Joseph C.; Seyfried, Thomas N.; Donohue, Joseph P.; Bost, Jeffrey

2015-01-01

Glioblastoma multiforme (GBM) is an aggressive and nearly uniformly fatal malignancy of the central nervous system. Despite extensive research and clinical trials over the past 50 years, very little progress has been made to significantly alter its lethal prognosis. The current standard of care (SOC) includes maximal surgical resection, radiation therapy and chemotherapy and temozolomide (TMZ), including the selective use of glucocorticoids for symptom control. These same treatments, however, have the potential to create an environment that may actually facilitate tumor growth and survival. Research investigating the unique metabolic needs of tumor cells has led to the proposal of a new metabolic treatment for various cancers including GBMs that may enhance the effectiveness of the SOC. The goal of metabolic cancer therapy is to restrict GBM cells of glucose, their main energy substrate. By recognizing the underlying energy production requirements of cancer cells, newly proposed metabolic therapy is being used as an adjunct to standard GBM therapies. This review will discuss the calorie restricted ketogenic diet (CR-KD) as a promising potential adjunctive metabolic therapy for patients with GBMs. The effectiveness of the CR-KD is based on the “Warburg Effect” of cancer metabolism and the microenvironment of GBM tumors. We will review recent case reports, clinical studies, review articles, and animal model research using the CR-KD and explain the principles of the Warburg Effect as it relates to CR-KD and GBMs. PMID:25949849

MO-A-BRD-02: Physics Perspective

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

Kappadath, S.

2015-06-15

Yttrium-90 (Y90) microsphere therapy, a form of radiation therapy, is an increasingly popular option for care of patients with liver metastases or unresectable hepatocellular carcinoma. The therapy directly delivers Y90 microspheres via the hepatic artery to disease sites. Following delivery, a vast majority of microspheres preferentially lodge in the capillary vessels due to their embolic size and targeted trans-arterial delivery – depositing up to 90% of its energy in the first 5 mm of tissue. There have been a number of advances in tomographic imaging within both interventional radiology and nuclear medicine that has advanced therapy planning techniques. Quantitative imagingmore » of Y90 microsphere distribution post-therapy has also seen innovations that have led to improvements in tumor dosimetry and characterization of tumor response. A review of current trends and recent innovation in Y90 microsphere therapies will be presented. Learning Objectives: To present the imaging requirements for Y90 microsphere therapy planning To explain the standard dosimetry models used in Y90 microsphere therapy planning To report on advances in imaging for therapy planning and posttherapy assessment of tumor dosimetry and response.« less

MO-A-BRD-01: Clinical Perspective

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

Mahvash, A.

2015-06-15

Yttrium-90 (Y90) microsphere therapy, a form of radiation therapy, is an increasingly popular option for care of patients with liver metastases or unresectable hepatocellular carcinoma. The therapy directly delivers Y90 microspheres via the hepatic artery to disease sites. Following delivery, a vast majority of microspheres preferentially lodge in the capillary vessels due to their embolic size and targeted trans-arterial delivery – depositing up to 90% of its energy in the first 5 mm of tissue. There have been a number of advances in tomographic imaging within both interventional radiology and nuclear medicine that has advanced therapy planning techniques. Quantitative imagingmore » of Y90 microsphere distribution post-therapy has also seen innovations that have led to improvements in tumor dosimetry and characterization of tumor response. A review of current trends and recent innovation in Y90 microsphere therapies will be presented. Learning Objectives: To present the imaging requirements for Y90 microsphere therapy planning To explain the standard dosimetry models used in Y90 microsphere therapy planning To report on advances in imaging for therapy planning and posttherapy assessment of tumor dosimetry and response.« less

Interferon-based anti-viral therapy for hepatitis C virus infection after renal transplantation: an updated meta-analysis.

PubMed

Wei, Fang; Liu, Junying; Liu, Fen; Hu, Huaidong; Ren, Hong; Hu, Peng

2014-01-01

Hepatitis C virus (HCV) infection is highly prevalent in renal transplant (RT) recipients. Currently, interferon-based (IFN-based) antiviral therapies are the standard approach to control HCV infection. In a post-transplantation setting, however, IFN-based therapies appear to have limited efficacy and their use remains controversial. The present study aimed to evaluate the efficacy and safety of IFN-based therapies for HCV infection post RT. We searched Pubmed, Embase, Web of Knowledge, and The Cochrane Library (1997-2013) for clinical trials in which transplant patients were given Interferon (IFN), pegylated interferon (PEG), interferon plus ribavirin (IFN-RIB), or pegylated interferon plus ribavirin (PEG-RIB). The Sustained Virological Response (SVR) and/or drop-out rates were the primary outcomes. Summary estimates were calculated using the random-effects model of DerSimonian and Laird, with heterogeneity and sensitivity analysis. We identified 12 clinical trials (140 patients in total). The summary estimate for SVR rate, drop-out rate and graft rejection rate was 26.6% (95%CI, 15.0-38.1%), 21.1% (95% CI, 10.9-31.2%) and 4% (95%CI: 0.8%-7.1%), respectively. The overall SVR rate in PEG-based and standard IFN-based therapy was 40.6% (24/59) and 20.9% (17/81), respectively. The most frequent side-effect requiring discontinuation of treatment was graft dysfunction (14 cases, 45.1%). Meta-regression analysis showed the covariates included contribute to the heterogeneity in the SVR logit rate, but not in the drop-out logit rate. The sensitivity analyses by the random model yielded very similar results to the fixed-effects model. IFN-based therapy for HCV infection post RT has poor efficacy and limited safety. PEG-based therapy is a more effective approach for treating HCV infection post-RT than standard IFN-based therapy. Future research is required to develop novel strategies to improve therapeutic efficacy and tolerability, and reduce the liver-related morbidity and mortality in this important patient population.

The Residual Risk Reduction Initiative: a call to action to reduce residual vascular risk in patients with dyslipidemia.

PubMed

Fruchart, Jean-Charles; Sacks, Frank; Hermans, Michel P; Assmann, Gerd; Brown, W Virgil; Ceska, Richard; Chapman, M John; Dodson, Paul M; Fioretto, Paola; Ginsberg, Henry N; Kadowaki, Takashi; Lablanche, Jean-Marc; Marx, Nikolaus; Plutzky, Jorge; Reiner, Zeljko; Rosenson, Robert S; Staels, Bart; Stock, Jane K; Sy, Rody; Wanner, Christoph; Zambon, Alberto; Zimmet, Paul

2008-11-17

Despite achieving targets for low-density lipoprotein (LDL) cholesterol, blood pressure, and glycemia in accordance with current standards of care, patients with dyslipidemia remain at high residual risk of vascular events. Atherogenic dyslipidemia, characterized by elevated triglycerides and low levels of high-density lipoprotein (HDL) cholesterol, often with elevated apolipoprotein B and non-HDL cholesterol, is common in patients with established cardiovascular disease (CVD), type 2 diabetes mellitus, or metabolic syndrome and contributes to both macrovascular and microvascular residual risk. However, atherogenic dyslipidemia is largely underdiagnosed and undertreated in clinical practice. The Residual Risk Reduction Initiative (R3i) was established to address this highly relevant clinical issue. The aims of this position paper are (1) to highlight evidence that atherogenic dyslipidemia is associated with residual macrovascular and microvascular risk in patients at high risk for CVD, despite current standards of care for dyslipidemia and diabetes; and (2) to recommend therapeutic intervention for reducing this residual vascular risk supported by evidence and expert consensus. Lifestyle modification with nutrition and exercise is an important, effective, and underutilized first step in reducing residual vascular risk. Therapeutic intervention aimed at achievement of all lipid targets is also often required. Combination lipid-modifying therapy, with the addition of niacin, a fibrate, or omega-3 fatty acids to statin therapy, increases the probability of achieving all lipid goals. Outcomes studies are in progress to evaluate whether these combination treatment strategies translate to a clinical benefit greater than that achieved with statins alone. The R3i highlights the need to address with lifestyle and/or pharmacotherapy the high level of residual risk of CVD events and microvascular complications among patients with dyslipidemia receiving therapy for high levels of LDL cholesterol and for diabetes in accordance with current standards of care.

Molecular Biology in Pediatric High-Grade Glioma: Impact on Prognosis and Treatment.

PubMed

Rizzo, Daniela; Ruggiero, Antonio; Martini, Maurizio; Rizzo, Valentina; Maurizi, Palma; Riccardi, Riccardo

2015-01-01

High-grade gliomas are the main cause of death in children with brain tumours. Despite recent advances in cancer therapy, their prognosis remains poor and the treatment is still challenging. To date, surgery followed by radiotherapy and temozolomide is the standard therapy. However, increasing knowledge of glioma biology is starting to impact drug development towards targeted therapies. The identification of agents directed against molecular targets aims at going beyond the traditional therapeutic approach in order to develop a personalized therapy and improve the outcome of pediatric high-grade gliomas. In this paper, we critically review the literature regarding the genetic abnormalities implicated in the pathogenesis of pediatric malignant gliomas and the current development of molecularly targeted therapies. In particular, we analyse the impact of molecular biology on the prognosis and treatment of pediatric high-grade glioma, comparing it to that of adult gliomas.

Molecular Biology in Pediatric High-Grade Glioma: Impact on Prognosis and Treatment

PubMed Central

Rizzo, Daniela; Ruggiero, Antonio; Martini, Maurizio; Rizzo, Valentina; Maurizi, Palma; Riccardi, Riccardo

2015-01-01

High-grade gliomas are the main cause of death in children with brain tumours. Despite recent advances in cancer therapy, their prognosis remains poor and the treatment is still challenging. To date, surgery followed by radiotherapy and temozolomide is the standard therapy. However, increasing knowledge of glioma biology is starting to impact drug development towards targeted therapies. The identification of agents directed against molecular targets aims at going beyond the traditional therapeutic approach in order to develop a personalized therapy and improve the outcome of pediatric high-grade gliomas. In this paper, we critically review the literature regarding the genetic abnormalities implicated in the pathogenesis of pediatric malignant gliomas and the current development of molecularly targeted therapies. In particular, we analyse the impact of molecular biology on the prognosis and treatment of pediatric high-grade glioma, comparing it to that of adult gliomas. PMID:26448930

Molecular techniques for the personalised management of patients with chronic myeloid leukaemia.

PubMed

Alikian, Mary; Gale, Robert Peter; Apperley, Jane F; Foroni, Letizia

2017-03-01

Chronic myeloid leukemia (CML) is the paradigm for targeted cancer therapy. RT-qPCR is the gold standard for monitoring response to tyrosine kinase-inhibitor (TKI) therapy based on the reduction of blood or bone marrow BCR-ABL1 . Some patients with CML and very low or undetectable levels of BCR-ABL1 transcripts can stop TKI-therapy without CML recurrence. However, about 60 percent of patients discontinuing TKI-therapy have rapid leukaemia recurrence. This has increased the need for more sensitive and specific techniques to measure residual CML cells. The clinical challenge is to determine when it is safe to stop TKI-therapy. In this review we describe and critically evaluate the current state of CML clinical management, different technologies used to monitor measurable residual disease (MRD) focus on comparingRT-qPCR and new methods entering clinical practice. We discuss advantages and disadvantages of new methods.

[Modern therapy of chronic myeloid leukemia: an example for paradigma shift in hemato-oncology].

PubMed

Leitner, A A; Hehlmann, R

2011-02-01

Chronic myeloid leukemia (CML) is exceptional amongst neoplasias since its underlying pathomechanism has been elucidated, and potent well tolerated targeted drugs, the tyrosine kinase inhibitors (TKI), are available for treatment. They convincingly improve prognosis while retaining good quality of life. Aims of therapy are complete remissions as well as prolongation of life and cure. Imatinib 400 mg per day is current standard therapy. There are hints for a better outcome with a higher initial imatinib dose or with combination therapy. Even after achievement of complete molecular response continuous therapy might be necessary in most cases. In case of imatinib intolerance or failure, the second generation TKI dasatinib and nilotinib and allogeneic stem cell transplantation are available. The use of second generation TKI as first line treatment might further improve prognosis. The therapeutic response should be regularly monitored according to international recommendations.

Horticultural therapy for schizophrenia.

PubMed

Liu, Yan; Bo, Li; Sampson, Stephanie; Roberts, Samantha; Zhang, Guoyou; Wu, Weiping

2014-05-19

Horticultural therapy is defined as the process of utilising fruits, vegetables, flowers and plants facilitated by a trained therapist or healthcare provider, to achieve specific treatment goals or to simply improve a person's well-being. It can be used for therapy or rehabilitation programs for cognitive, physical, social, emotional, and recreational benefits, thus improving the person's body, mind and spirit. Between 5% to 15% of people with schizophrenia continue to experience symptoms in spite of medication, and may also develop undesirable adverse effects, horticultural therapy may be of value for these people. To evaluate the effects of horticultural therapy for people with schizophrenia or schizophrenia-like illnesses compared with standard care or other additional psychosocial interventions. We searched the Cochrane Schizophrenia Group Trials Register (Janurary 2013) and supplemented this by contacting relevant study authors, and manually searching reference lists. We included one randomised controlled trial (RCT) comparing horticultural therapy plus standard care with standard care alone for people with schizophrenia. We reliably selected, quality assessed and extracted data. For continuous outcomes, we calculated a mean difference (MD) and for binary outcomes we calculated risk ratio (RR), both with 95% confidence intervals (CI). We assessed risk of bias and created a 'Summary of findings' table using the GRADE (Grades of Recommendation, Assessment, Development and Evaluation) approach. We included one single blind study (total n = 24). The overall risk of bias in the study was considered to be unclear although the randomisation was adequate. It compared a package of horticultural therapy which consisted of one hour per day of horticultural activity plus standard care with standard care alone over two weeks (10 consecutive days) with no long-term follow-up. Only two people were lost to follow-up in the study, both in the horticultural therapy group (1 RCT n = 24,RR 5.00 95% CI 0.27 to 94.34, very low quality evidence). There was no clear evidence of a difference in Personal Wellbeing Index (PWI-C) change scores between groups, however confidence intervals were wide (1 RCT n = 22, MD -0.90 95% CI -10.35 to 8.55, very low quality evidence). At the end of treatment, the Depression Anxiety Stress Scale (DASS21) change scores in horticultural therapy group were greater than that in the control group (1 RCT n = 22, MD -23.70 CI -35.37 to - 12.03, very low quality evidence). The only included study did not report on adverse effects of interventions. Based on the current very low quality data, there is insufficient evidence to draw any conclusions on benefits or harms of horticultural therapy for people with schizophrenia. This therapy remains unproven and more and larger randomised trials are needed to increase high quality evidence in this area.

Handwriting and Common Core State Standards: Teacher, Occupational Therapist, and Administrator Perceptions From New York State Public Schools.

PubMed

Collette, Debra; Anson, Kylie; Halabi, Nora; Schlierman, April; Suriner, Allison

Handwriting is the cornerstone of written performance and communication for school-age children. This mixed-methods study explored the impact of Common Core State Standards on handwriting instruction and its effects on perceptions regarding children's written responses in elementary school. Using surveys and interviews of elementary teachers, occupational therapists, and administrators in New York State public schools, we sought to understand current trends in handwriting instruction, changes in time spent on handwriting instruction in the classroom, supports offered to students who did not meet expectations for handwriting, and the impact of Common Core on children's written expression. Themes emerged revealing decreased handwriting instruction time and inconsistent use of handwriting instructional programs in the classroom after implementation of Common Core. Handwriting should be considered as a greater component in the foundational standards in Common Core. Occupational therapy services can support handwriting instruction implementation. Copyright © 2017 by the American Occupational Therapy Association, Inc.

Lenalidomide in multiple myeloma: an evidence-based review of its role in therapy

PubMed Central

Richardson, Paul; Mitsiades, Constantine; Laubach, Jacob; Schlossman, Robert; Ghobrial, Irene; Hideshima, Teru; Munshi, Nikhil; Anderson, Kenneth

2010-01-01

Introduction: Multiple myeloma (MM) is a relatively common and incurable hematological malignancy. Currently, there is no single standard therapy, with choice of treatment dependent on individual patient factors. Lenalidomide is an immunomodulatory drug with potent antitumor, antiangiogenic, immunomodulatory, and proapoptotic activity in MM. Aims: To evaluate the evidence for the use of lenalidomide in its current indication in relapsed or refractory MM, and additionally its investigational use for the treatment of newly diagnosed MM. Evidence review: In patients with relapsed and refractory MM, adding lenalidomide to high-dose dexamethasone significantly improves response rates and time-to-progression, relative to high-dose dexamethasone alone. This translates into a significant extension of overall survival (with a median extension of 9.1 months in a pivotal phase III study). Outcome is independent of patient age, number of previous therapies, type of previous therapy (including thalidomide or autologous stem cell transplantation), renal impairment, and β2-microglobulin level. Evidence suggests that combining lenalidomide with low-dose dexamethasone improves outcomes in patients with newly diagnosed disease and is superior to lenalidomide combined with high-dose dexamethasone. Myelosuppression is the predominant toxicity observed, although some studies have shown high incidences of venous thromboembolism in the absence of prophylactic antithrombotic anticoagulation therapy. There is currently only limited evidence regarding the health economics of lenalidomide. Role in therapy: The encouraging results obtained with lenalidomide alone and in combination with dexamethasone in patients with relapsed or refractory MM have led to its adoption as a recommended therapy in patients who have received at least one prior treatment. Emerging evidence supports the ongoing investigation of lenalidomide in combination with low-dose dexamethasone, and in other combinations including bortezomib, for use both in relapsed, refractory, and newly diagnosed MM. PMID:20694078

[Current views of nutritional therapy].

PubMed

Pogozheva, A V; Kaganov, B S

2009-01-01

Epidemiologic studies in the Research Institute of Nutrition showed that dietary patterns of the Russian population are on the whole at variance with the balanced feeding formula largely due to excessive consumption of animal fat, insufficient consumption of proteins, vitamins, micro- and macroelements, polyunsaturated fatty acids, and dietary fibers. It is estimated that over 70% of total lethality in this country is due to diseases directly related to improper feeding (the so-called alimentary-dependent diseases), cardiovascular disorders, some neoplasms, diabetes mellitus, etc. Dietary therapy adjusted to specific pathogenetic features, clinical picture, stage of the disease, character of metabolic disorders in individual patients is an important factor having versatile beneficial effects on the patient's health, correcting metabolic problems, and improving quality of life. Decree No 330 of August 5, 2003 "On measures to improve nutritional therapy in medical institutions of the Russian Federation" introduced a new nomenclature of standard diets based on chemical composition of separate foods and the previously used system of numbered diets. Modern dietary therapy includes not only standard and special diets but also specific products to be used in concrete clinical conditions, enteral and parenteral nutrition, biologically active food additives, etc.

An Analysis of Laser Therapy for the Treatment of Nonmelanoma Skin Cancer.

PubMed

Soleymani, Teo; Abrouk, Michael; Kelly, Kristen M

2017-05-01

Skin cancer remains the most prevalent type of cancer in the United States, and its burden on the health care system remains substantial. Standard treatments such as cryosurgery, electrodessication and curettage, topical and photodynamic therapies, and surgical excision including Mohs micrographic surgery are not without inherent morbidity, including risk of bleeding, infection, and scar. Lasers may be an alternative for treatment of nonmelanoma skin cancer, and this paper reviews this therapeutic option. A comprehensive search in the Cochrane Library, MEDLINE, and PUBMED databases was performed to identify relevant literature investigating the role of laser therapy in the treatment of nonmelanoma skin cancer. New literature regarding laser treatment of nonmelanoma skin cancer is emerging, demonstrating promising clinical outcomes. The greatest efficacy has been seen with vascular-selective and ablative lasers in the treatment of basal cell carcinomas. Some success has been reported for laser treatment of squamous cell carcinoma, but data are less convincing. In summary, laser therapy offers an alternative treatment option for nonmelanoma skin cancer; however, its clinical efficacy is variable and, at this time, remains less than currently accepted standards of care. Further studies are needed to optimize parameters, determine maximum efficacy, and provide long-term follow-up.

Cost-effectiveness of supervised exercise therapy in heart failure patients.

PubMed

Kühr, Eduardo M; Ribeiro, Rodrigo A; Rohde, Luis Eduardo P; Polanczyk, Carisi A

2011-01-01

Exercise therapy in heart failure (HF) patients is considered safe and has demonstrated modest reduction in hospitalization rates and death in recent trials. Previous cost-effectiveness analysis described favorable results considering long-term supervised exercise intervention and significant effectiveness of exercise therapy; however, these evidences are now no longer supported. To evaluate the cost-effectiveness of supervised exercise therapy in HF patients under the perspective of the Brazilian Public Healthcare System. We developed a Markov model to evaluate the incremental cost-effectiveness ratio of supervised exercise therapy compared to standard treatment in patients with New York Heart Association HF class II and III. Effectiveness was evaluated in quality-adjusted life years in a 10-year time horizon. We searched PUBMED for published clinical trials to estimate effectiveness, mortality, hospitalization, and utilities data. Treatment costs were obtained from published cohort updated to 2008 values. Exercise therapy intervention costs were obtained from a rehabilitation center. Model robustness was assessed through Monte Carlo simulation and sensitivity analysis. Cost were expressed as international dollars, applying the purchasing-power-parity conversion rate. Exercise therapy showed small reduction in hospitalization and mortality at a low cost, an incremental cost-effectiveness ratio of Int$26,462/quality-adjusted life year. Results were more sensitive to exercise therapy costs, standard treatment total costs, exercise therapy effectiveness, and medications costs. Considering a willingness-to-pay of Int$27,500, 55% of the trials fell below this value in the Monte Carlo simulation. In a Brazilian scenario, exercise therapy shows reasonable cost-effectiveness ratio, despite current evidence of limited benefit of this intervention. Copyright © 2011 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

Interferential and horizontal therapies in chronic low back pain due to multiple vertebral fractures: a randomized, double blind, clinical study.

PubMed

Zambito, A; Bianchini, D; Gatti, D; Rossini, M; Adami, S; Viapiana, O

2007-11-01

Chronic low back pain due to multiple vertebral fractures is of difficult management. Electrical nerve stimulation is frequently used, but its efficacy has never been properly evaluated. In a randomized placebo-controlled clinical trial, we have shown that both interferential currents and horizontal therapy are more effective than placebo for functional. Multiple vertebral fractures almost invariably ensue in chronic low back pain that remains of difficult management. Electrical nerve stimulation is frequently used but its efficacy has never been properly evaluated. One hundred and fifteen women with chronic back pain due to previous multiple vertebral osteoporotic fractures (CBPMF) were randomly assigned to either interferential currents (IFT), horizontal therapy (HT) or sham HT administered for 30 minutes daily for 5 days per week for two weeks together with a standard exercise program. Efficacy assessment was obtained at baseline and at week 2, 6 and 14 and included a functional questionnaire (Backill), the standard visual analog scale (VAS) and the mean analgesic consumption. At week 2 a significant and similar improvement in both the VAS and Backill score was observed in the three groups. The two scores continued to improve in the two active groups with changes significantly (p < 0.001) greater than those observed in control patients at week 6 and 14. The use of analgesic medications improved only in the HT group. This randomized double-blind controlled study provides the first evidence that IFT and HT therapy are significantly effective in alleviating both pain and disability in patients with CBPMF.

Stem-Cell Therapy Advances in China.

PubMed

Hu, Lei; Zhao, Bin; Wang, Songlin

2018-02-01

Stem-cell therapy is a promising method for treating patients with a wide range of diseases and injuries. Increasing government funding of scientific research has promoted rapid developments in stem-cell research in China, as evidenced by the substantial increase in the number and quality of publications in the past 5 years. Multiple high-quality studies have been performed in China that concern cell reprogramming, stem-cell homeostasis, gene modifications, and immunomodulation. The number of translation studies, including basic and preclinical investigations, has also increased. Around 100 stem-cell banks have been established in China, 10 stem-cell drugs are currently in the approval process, and >400 stem cell-based clinical trials are currently registered in China. With continued state funding, advanced biotechnical support, and the development of regulatory standards for the clinical application of stem cells, further innovations are expected that will lead to a boom in stem-cell therapies. This review highlights recent achievements in stem-cell research in China and discusses future prospects.

Targets for Current Pharmacological Therapy in Cholesterol Gallstone Disease

PubMed Central

Di Ciaula, Agostino; Wang, David Q.-H.; Wang, Helen H.; Bonfrate, Leonilde; Portincasa, Piero

2010-01-01

Summary Gallstone disease is a frequent condition throughout the world and cholesterol stones are the most frequent form in western countries. Current standard treatment of symptomatic gallstone subjects remains laparoscopic cholecystectomy. The selection of patients amenable for non-surgical, medical therapy is of key importance: a careful analysis should consider the natural history of the disease and the overall costs of therapy. Only patients with mild symptoms and small, uncalcified cholesterol gallstones in a functioning gallbladder with a patent cystic duct will be considered for oral litholysis by the hydrophilic ursodeoxycholic acid (UDCA) hopefully leading to cholesterol desaturation of bile and progressive stone dissolution. Recent studies have raised the possibility that cholesterol-lowering agents which inhibit hepatic cholesterol synthesis (statins) or intestinal cholesterol absorption (ezetimibe), or drugs acting on specific nuclear receptors involved in cholesterol and bile acid homeostasis may offer, alone or in combination, additional medical therapeutic tools for treating cholesterol gallstones. Recent perspectives on medical treatment of cholesterol gallstone disease will be discussed in this chapter. PMID:20478485

Bioengineered Tooth Buds Exhibit Features of Natural Tooth Buds.

PubMed

Smith, E E; Angstadt, S; Monteiro, N; Zhang, W; Khademhosseini, A; Yelick, P C

2018-06-01

Tooth loss is a significant health issue currently affecting millions of people worldwide. Artificial dental implants, the current gold standard tooth replacement therapy, do not exhibit many properties of natural teeth and can be associated with complications leading to implant failure. Here we propose bioengineered tooth buds as a superior alternative tooth replacement therapy. We describe improved methods to create highly cellularized bioengineered tooth bud constructs that formed hallmark features that resemble natural tooth buds such as the dental epithelial stem cell niche, enamel knot signaling centers, transient amplifying cells, and mineralized dental tissue formation. These constructs were composed of postnatal dental cells encapsulated within a hydrogel material that were implanted subcutaneously into immunocompromised rats. To our knowledge, this is the first report describing the use of postnatal dental cells to create bioengineered tooth buds that exhibit evidence of these features of natural tooth development. We propose future bioengineered tooth buds as a promising, clinically relevant tooth replacement therapy.

Current issues with blood transfusions in sickle cell disease.

PubMed

Vichinsky, E P

2001-01-01

With increased recognition of the profound morbidity of sickle cell disease and with growing evidence of the efficacy of transfusion therapy in prevention and treatment of sickle cell complications, most patients now receive intermittent transfusion therapy. The purpose of this report is to review blood component therapy and Its risks for sickle cell patients. Packed red cells are the preferred blood component. Leukocyte-reduced units should be standard because of their beneficial effects in reducing alloimmunization, transfusion reactions, platelet refractoriness, and infection transmission. The use of washed, frozen, or Irradiated units is limited to specific problems. Sickle trait-positive units function normally, but because of difficulties with calculating hemoglobin S percentages and leukocyte filters, they are not routinely used. Transfusion-acquired infections have shown a marked decrease but still present a major risk. Viral hepatitis transmission is currently low, but at least 10% of adult sickle cell patients are hepatitis C positive, and they often have liver damage. Although bacterial infections are rare, they account for 16% of transfusion-related fatalities. Patients who are iron overloaded are particularly vulnerable to Yersina enterocolitica. Red cell alloimmunization is a serious problem that could potentially affect 50% of transfused patients. However, preventive phenotypic matching for common antigens can minimize alloimmunization; limited matching for at least E, C, and K has become the standard of care. Recently, more patients are being identified who have developed red cell autoantibodies, which can mask alloantibodies and occasionally are hemolytic. Careful laboratory evaluation of all cases is essential. Transfusions also may trigger sickle cell events, including pain crises, stroke, and acute pulmonary deterioration. In part, these are induced by blood viscosity and increased blood pressure. Diuretic therapy and close monitoring of transfusion volume and vital signs can minimize these events. In summary, transfusion therapy carries risks, but the routine use of leukocyte-reduced, phenotypically matched units in conjunction with close monitoring of patients can make transfusion therapy safer.

Development of job standards for clinical nutrition therapy for dyslipidemia patients.

PubMed

Kang, Min-Jae; Seo, Jung-Sook; Kim, Eun-Mi; Park, Mi-Sun; Woo, Mi-Hye; Ju, Dal-Lae; Wie, Gyung-Ah; Lee, Song-Mi; Cha, Jin-A; Sohn, Cheong-Min

2015-04-01

Dyslipidemia has significantly contributed to the increase of death and morbidity rates related to cardiovascular diseases. Clinical nutrition service provided by dietitians has been reported to have a positive effect on relief of medical symptoms or reducing the further medical costs. However, there is a lack of researches to identify key competencies and job standard for clinical dietitians to care patients with dyslipidemia. Therefore, the purpose of this study was to analyze the job components of clinical dietitian and develop the standard for professional practice to provide effective nutrition management for dyslipidemia patients. The current status of clinical nutrition therapy for dyslipidemia patients in hospitals with 300 or more beds was studied. After duty tasks and task elements of nutrition care process for dyslipidemia clinical dietitians were developed by developing a curriculum (DACUM) analysis method. The developed job standards were pretested in order to evaluate job performance, difficulty, and job standards. As a result, the job standard included four jobs, 18 tasks, and 53 task elements, and specific job description includes 73 basic services and 26 recommended services. When clinical dietitians managing dyslipidemia patients performed their practice according to this job standard for 30 patients the job performance rate was 68.3%. Therefore, the job standards of clinical dietitians for clinical nutrition service for dyslipidemia patients proposed in this study can be effectively used by hospitals.

Islet cell transplant: Update on current clinical trials

PubMed Central

Schuetz, Christian; Markmann, James F.

2016-01-01

In the last 15 years clinical islet transplantation has made the leap from experimental procedure to standard of care for a highly selective group of patients. Due to a risk-benefit calculation involving the required systemic immunosuppression the procedure is only considered in patients with type 1 diabetes, complicated by severe hypoglycemia or end stage renal disease. In this review we summarize current outcomes of the procedure and take a look at ongoing and future improvements and refinements of beta cell therapy. PMID:28451515

Targeted therapy for non-small cell lung cancer: current standards and the promise of the future

PubMed Central

Chan, Bryan A.

2015-01-01

In recent years, there has been a major paradigm shift in the management of non-small cell lung cancer (NSCLC). NSCLC should now be further sub-classified by histology and driver mutation if one is known or present. Translational research advances now allow such mutations to be inhibited by either receptor monoclonal antibodies (mAb) or small molecule tyrosine kinase inhibitors (TKI). Whilst empirical chemotherapy with a platinum-doublet remains the gold standard for advanced NSCLC without a known driver mutation, targeted therapy is pushing the boundary to significantly improve patient outcomes and quality of life. In this review, we will examine the major subtypes of oncogenic drivers behind NSCLC as well as the development of targeted agents available to treat them both now and in the foreseeable future. PMID:25806345

Relapse following antithyroid drug therapy for Graves' hyperthyroidism.

PubMed

Laurberg, Peter; Krejbjerg, Anne; Andersen, Stine Linding

2014-10-01

In most patients with hyperthyroidism caused by Graves' disease, antithyroid drug (ATD) therapy is followed by a gradual amelioration of the autoimmune abnormality, but about half of the patients will experience relapse of hyperthyroidism when the ATDs are withdrawn after a standard 1 to 2 years of therapy. This is a major drawback of ATD therapy, and a major concern to patients. We review current knowledge on how to predict and possibly reduce the risk of such relapse. Several patient and disease characteristics, as well as environmental factors and duration of ATD therapy, may influence the risk of relapse after ATD withdrawal. Depending on the presence of such factors, the risk of relapse after ATD withdrawal may vary from around 10 to 90%. Risk factors for relapse should be taken into account when choosing between therapeutic modalities in a patient with newly diagnosed disease, and also when discussing duration of ATD therapy. Prolonged low-dose ATD therapy may be feasible in patients with high risk of relapse, such as children and patients with active Graves' orbitopathy, and in patients with previous relapse who prefer such therapy rather than surgery or radioiodine.

Status of and candidates for cell therapy in liver cirrhosis: overcoming the "point of no return" in advanced liver cirrhosis.

PubMed

Terai, Shuji; Tsuchiya, Atsunori

2017-02-01

The treatment of liver cirrhosis is currently being standardized and developed specifically to reduce activation of hepatic stellate cells (HSCs), inhibit fibrosis, increase degradation of matrix components, and reduce activated myofibroblasts. Cell therapy can be applied in the treatment of liver cirrhosis; however, the characteristic features of this therapy differ from those of other treatments because of the involvement of a living body origin and production of multiple cytokines, chemokines, matrix metalloproteinases (MMPs), and growth factors. Thus, cell therapies can potentially have multiple effects on the damaged liver, including alleviating liver cirrhosis and stimulating liver regeneration with affecting the host cells. Cell therapies initially involved autologous bone marrow cell infusion, and have recently developed to include the use of specific cells such as mesenchymal stem cells and macrophages. The associated molecular mechanisms, routes of administration, possibility of allogeneic cell therapy, and host conditions appropriate for cell therapies are now being extensively analyzed. In this review, we summarize the status and future prospects of cell therapy for liver cirrhosis.

Music as a therapy: role in psychiatry.

PubMed

Solanki, Madhusudan Singh; Zafar, Mehnaz; Rastogi, Rajesh

2013-06-01

Music is popularly believed to usher in bliss and serenity, and healing is considered its natural quality. It has an emotionally charging charisma of its own, that we all as listeners might have experienced at times. Music has been there with mankind since the beginning of history, but where does it stand as a therapy? Is there any evidence base? How this therapy came into being and how it has evolved, and what the old and current research says about its role in psychiatric disorders. This review tries to explore these questions and arrives at a conclusion that music certainly promises more than just entertainment, and evidence so far suggests music therapy can be beneficial in the treatment of psychiatric disorders, as a cost effective noninvasive adjunct to standard therapy in a variety of settings and patient groups, yet more validated scientific research is still required to establish it as a sole quantified therapy. Copyright © 2012 Elsevier B.V. All rights reserved.

Monitoring of anticoagulant therapy in heart disease: considerations for the current assays.

PubMed

Boroumand, Mohammadali; Goodarzynejad, Hamidreza

2010-01-01

Clinicians should be aware of new developments to familiarize themselves with pharmacokinetic and pharmacodynamic characteristics of new anticoagulant agents to appropriately and safely use them. For the moment, cardiologists and other clinicians also require to master currently available drugs, realizing the mechanism of action, side effects, and laboratory monitoring to measure their anticoagulant effects. Warfarin and heparin have narrow therapeutic window with high inter- and intra-patient variability, thereby the use of either drug needs careful laboratory monitoring and dose adjustment to ensure proper antithrombotic protection while minimizing the bleeding risk. The prothrombin time (PT) and the activated partial thromboplastin time (aPTT) are laboratory tests commonly used to monitor warfarin and heparin, respectively. These two tests depend highly on the combination of reagent and instrument utilized. Results for a single specimen tested in different laboratories are variable; this is mostly attributable to the specific reagents and to a much lesser degree to the instrument used. The PT stands alone as the single coagulation test that has undergone the most extensive attempt at assay standardization. The international normalized ratio (INR) was introduced to "normalize" all PT reagents to a World Health Organization (WHO) reference thromboplastin preparation standard, such that a PT measured anywhere in the world would result in an INR value similar to that which would have been achieved had the WHO reference thromboplastin been utilized. However, INRs are reproducible between laboratories for only those patients who are stably anticoagulated with vitamin K antagonists (VKAs) (i.e., at least 6 weeks of VKA therapy), and are not reliable or reproducible between laboratories for patients for whom VKA therapy has recently been started or any other clinical conditions associated with a prolonged PT such as liver disease, disseminated intravascular coagulation, and congenital factor deficiencies. In contrast to marked progress in the standardization of PT reagents for INR reporting, no standardization system has been globally adopted for standardization of PTT reagents. Recently College of American Pathologists recommend that individual laboratories establish their own therapeutic range by using aPTT values calibrated against accepted therapeutic unfractionated heparin (UFH) levels calibrated against accepted therapeutic UFH levels performing anti-Xa test (which is the most accurate assay for monitoring UFH therapy).Herein, we review recent data on the monitoring of conventional anticoagulant agents. Marked interlaboratory variability still exists for PT, INR, and PTT tests. Further research should be focused on improving the standardization and calibration of these assays.

Correction of anemia in a transfusion-dependent patient with primary myelofibrosis receiving iron chelation therapy with deferasirox (Exjade®, ICL670)

PubMed Central

Di Tucci, Anna Angela; Murru, Roberta; Alberti, Daniele; Rabault, Bertrand; Deplano, Simona; Angelucci, Emanuele

2007-01-01

Transfusional iron overload in patients with chronic anemias can result in multiple organ failure. Experience in the management of iron overload in patients with myelodysplastic syndromes is limited, as many do not receive chelation therapy due to short-life expectancy and the difficulties associated with the administration of the current reference standard chelator, deferoxamine. There have, however, been some reports of reduced transfusion requirement associated with chelation therapy in patients with myelodysplastic syndromes and myelofibrosis. Here, we discuss a patient with primary myelofibrosis and related transfusion-dependent anemia who received chelation therapy with the once-daily oral iron chelator, deferasirox. In addition to the reduced iron levels, the patient demonstrated an unexpected reduction in blood transfusion requirement, ultimately resulting in long-lasting transfusion-free survival. PMID:17391307

Radiation shielding design of a new tomotherapy facility.

PubMed

Zacarias, Albert; Balog, John; Mills, Michael

2006-10-01

It is expected that intensity modulated radiation therapy (IMRT) and image guided radiation therapy (IGRT) will replace a large portion of radiation therapy treatments currently performed with conventional MLC-based 3D conformal techniques. IGRT may become the standard of treatment in the future for prostate and head and neck cancer. Many established facilities may convert existing vaults to perform this treatment method using new or upgraded equipment. In the future, more facilities undoubtedly will be considering de novo designs for their treatment vaults. A reevaluation of the design principles used in conventional vault design is of benefit to those considering this approach with a new tomotherapy facility. This is made more imperative as the design of the TomoTherapy system is unique in several aspects and does not fit well into the formalism of NCRP 49 for a conventional linear accelerator.

Drugs for asthma

PubMed Central

Barnes, Peter J

2006-01-01

Current drug therapy for asthma is highly effective and has evolved from naturally occurring substances through logical pharmaceutical developments. Pharmacology has played a critical role in asthma drug development and several key experimental observations have been published in this journal. Understanding the pharmacology of effective drug therapies has also taught us much about the underlying mechanisms of asthma. β2-Adrenoceptor agonists are the most effective bronchodilators and evolved from catecholamines from the adrenal medulla, whereas corticosteroids, from the adrenal cortex, are by far the most effective controllers of the underlying inflammatory process in the airways. The current ‘gold standard' of asthma therapy is a combination inhaler containing a long-acting β2-agonist with a corticosteroid – an improved form of adrenal gland extract. Cromoglycate, derived from a plant product and theophylline, a dietary methyl xanthine, have also been extensively used in the therapy of asthma, but we still do not understand their molecular mechanisms. Pharmacology has played an important role in improving natural products to make effective long lasting and safe asthma therapies, but has so far been challenged to produce new classes of antiasthma therapy. The only novel class of antiasthma therapy introduced in the last 30 years are leukotriene antagonists, which are less effective than existing treatments. New, more specific, therapies targeted at specific cytokines are less effective than corticosteroids, whereas more effective therapies carry a risk of side effects that may not be acceptable. It seems likely that pharmacology, rather than molecular genetics, will remain the main approach to the further improvement of treatment for asthma. PMID:16402117

Regulation of stem cell-based therapies in Canada: current issues and concerns.

PubMed

von Tigerstrom, Barbara; Nguyen, Thu Minh; Knoppers, Bartha Maria

2012-09-01

Stem cell therapies offer enormous potential for the treatment of a wide range of diseases and conditions. Despite the excitement over such advances, regulators are faced with the challenge of determining criteria to ensure stem cells and their products are safe and effective for human use. However, stem cell-based products and therapies present unique regulatory challenges because standard drug development models do not wholly apply given the complexity and diversity of these products and therapies. As a result, regulatory requirements are often unclear and ambiguous creating unnecessary barriers for research. In order to better understand the barriers that might affect Canadian stem cell researchers, we sought feedback from stakeholders regarding areas of uncertainty or concern about existing regulatory oversight of cell therapies. A selection of Canadian researchers and clinicians working in the area of stem cell research were interviewed to assess certain key questions: 1) whether current regulatory requirements are easily accessible and well understood; 2) whether regulatory requirements create important challenges or barriers; and 3) whether there is a need for further guidance on the issue. The results of this survey are summarized and compared to issues and concerns experienced in other countries, as reported in the literature, to identify challenges which may be on the horizon and to provide possible solutions for regulatory reform.

Lung cancer: biology and treatment options

PubMed Central

Hassan, Omer; Yang, Yi-Wei; Buchanan, Petra

2015-01-01

Lung cancer remains the leading cause of cancer mortality in men and women in the U.S. and worldwide. About 90% of lung cancer cases are caused by smoking and the use of tobacco products. However, other factors such as radon gas, asbestos, air pollution exposures, and chronic infections can contribute to lung carcinogenesis. In addition, multiple inherited and acquired mechanisms of susceptibility to lung cancer have been proposed. Lung cancer is divided into two broad histologic classes, which grow and spread differently: small-cell lung carcinomas (SCLC) and non-small cell lung carcinomas (NSCLC). Treatment options for lung cancer include surgery, radiation therapy, chemotherapy, and targeted therapy. Therapeutic-modalities recommendations depend on several factors, including the type and stage of cancer. Despite the improvements in diagnosis and therapy made during the past 25 years, the prognosis for patients with lung cancer is still unsatisfactory. The responses to current standard therapies are poor except for the most localized cancers. However, a better understanding of the biology pertinent to these challenging malignancies, might lead to the development of more efficacious and perhaps more specific drugs. The purpose of this review is to summarize the recent developments in lung cancer biology and its therapeutic strategies, and discuss the latest treatment advances including therapies currently under clinical investigation. PMID:26297204

[Clinical and health economic challenges of personalized medicine].

PubMed

Brüggenjürgen, B; Kornbluth, L; Ferrara, J V; Willich, S N

2012-05-01

Healthcare systems across the globe are currently challenged by aging populations, increases in chronic diseases and the difficult task of managing a healthcare budget. In this health economic climate, personalized medicine promises not only an improvement in healthcare delivery but also the possibility of more cost-effective therapies. It is important to remember, however, that personalized medicine has the potential to both increase and decrease costs. Each targeted therapy must be evaluated individually. However, standard clinical trial design is not suitable for personalized therapies. Therefore, both scientists and regulatory authorities will need to accept innovative study designs in order to validate personalized therapies. Hence correct economic evaluations are difficult to carry out due to lack of clear clinical evidence, longitudinal accounting and experience with patient/clinician behavior in the context of personalized medicine. In terms of reimbursement, payers, pharmaceutical companies and companion diagnostic manufacturers will also need to explore creative risk-sharing concepts. Germany is no exception to the challenges that face personalized medicine and for personalized medicine to really become the future of medicine many health economic challenges first need to be overcome. The health economic implications of personalized medicine remain unclear but it is certain that the expansion of targeted therapies in current healthcare systems will create a host of challenges.

[Hypoglossal nerve stimulation in patients with CPAP failure : Evolution of an alternative treatment for patients with obstructive sleep apnea].

PubMed

Heiser, C; Hofauer, B

2017-02-01

Obstructive sleep apnea (OSA) is a common disease in western industrialized countries with increasing prevalence. Gold standard of therapy is nocturnal positive pressure ventilation by continuous positive airway pressure (CPAP). Due to complications and side effects of ventilation, therapy adherence is limited. Recently an alternative surgical treatment has become available for these patients, which uses established techniques to stimulate the hypoglossus nerve to open the upper airway during sleep. The aim of this work is to provide an overview of the history and current state of scientific knowledge of this therapy in the treatment of OSA. Currently, two systems are available on the market: respiratory-driven hypoglossal nerve stimulation (Inspire Medical Systems) and continuous hypoglossal nerve stimulation (ImThera Medical). For respiratory-driven hypoglossal nerve stimulation, a solid body of evidence is available and the therapy has been investigated in numerous multicenter clinical studies with regard to safety and efficacy. Only a small number of publications is available for continuous hypoglossal nerve stimulation. At the end of the last century, promising clinical results were shown in the first patients treated with hypoglossal nerve stimulation. Consequent technological and scientific development of respiratory-driven hypoglossal nerve stimulation in recent years led to its implementation in today's clinical routine. This therapy significantly broadens the spectrum of therapies in the treatment of OSA, especially for patients with CPAP intolerance.

Next-generation prognostic assessment for diffuse large B-cell lymphoma

PubMed Central

Staton, Ashley D; Kof, Jean L; Chen, Qiushi; Ayer, Turgay; Flowers, Christopher R

2015-01-01

Current standard of care therapy for diffuse large B-cell lymphoma (DLBCL) cures a majority of patients with additional benefit in salvage therapy and autologous stem cell transplant for patients who relapse. The next generation of prognostic models for DLBCL aims to more accurately stratify patients for novel therapies and risk-adapted treatment strategies. This review discusses the significance of host genetic and tumor genomic alterations seen in DLBCL, clinical and epidemiologic factors, and how each can be integrated into risk stratification algorithms. In the future, treatment prediction and prognostic model development and subsequent validation will require data from a large number of DLBCL patients to establish sufficient statistical power to correctly predict outcome. Novel modeling approaches can augment these efforts. PMID:26289217

Next-generation prognostic assessment for diffuse large B-cell lymphoma.

PubMed

Staton, Ashley D; Koff, Jean L; Chen, Qiushi; Ayer, Turgay; Flowers, Christopher R

2015-01-01

Current standard of care therapy for diffuse large B-cell lymphoma (DLBCL) cures a majority of patients with additional benefit in salvage therapy and autologous stem cell transplant for patients who relapse. The next generation of prognostic models for DLBCL aims to more accurately stratify patients for novel therapies and risk-adapted treatment strategies. This review discusses the significance of host genetic and tumor genomic alterations seen in DLBCL, clinical and epidemiologic factors, and how each can be integrated into risk stratification algorithms. In the future, treatment prediction and prognostic model development and subsequent validation will require data from a large number of DLBCL patients to establish sufficient statistical power to correctly predict outcome. Novel modeling approaches can augment these efforts.

Challenges and opportunities in the management of Clostridium difficile infection.

PubMed

DuPont, Herbert L

2014-11-01

Clostridium difficile infection (CDI) is increasing in all regions of the world where sought. There is no gold standard for diagnosis of CDI, with available tests having limitations. Prevention of CDI will be seen with antibiotic stewardship, improved disinfection of hospitals and nursing homes, chemo- and immuno-prophylaxis and next generation probiotics. The important therapeutic agents are oral vancomycin and fidaxomicin with metronidazole being used only in mild cases or when oral therapy cannot be given. Current therapy of CDI for 10 days is associated with high rate of recurrence that may be prevented by prolonging initial therapy. Future treatment strategies will focus on drugs that inhibit C. difficile, reduce toxin activity and inflammation in the gut, and improve colonic flora diversity.

Radiation Therapy and Hearing Loss

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

Bhandare, Niranjan; Jackson, Andrew; Eisbruch, Avraham

2010-03-01

A review of literature on the development of sensorineural hearing loss after high-dose radiation therapy for head-and-neck tumors and stereotactic radiosurgery or fractionated stereotactic radiotherapy for the treatment of vestibular schwannoma is presented. Because of the small volume of the cochlea a dose-volume analysis is not feasible. Instead, the current literature on the effect of the mean dose received by the cochlea and other treatment- and patient-related factors on outcome are evaluated. Based on the data, a specific threshold dose to cochlea for sensorineural hearing loss cannot be determined; therefore, dose-prescription limits are suggested. A standard for evaluating radiation therapy-associatedmore » ototoxicity as well as a detailed approach for scoring toxicity is presented.« less

Management of Lung Cancer Invading the Superior Sulcus.

PubMed

Kratz, Johannes R; Woodard, Gavitt; Jablons, David M

2017-05-01

Superior sulcus tumors have posed a formidable therapeutic challenge since their original description by Pancoast and Tobias in the early twentieth century. Initial therapeutic efforts with radiotherapy were associated with high rates of relapse and mortality. Bimodality therapy with complete surgical resection in the 1960s paved the way for trimodality therapy as the current standard of care in the treatment of superior sulcus tumors. The evolution of treatment approaches over time has provided outcomes that come increasingly closer to rivaling those of similarly staged nonapical lung cancer. Copyright © 2017 Elsevier Inc. All rights reserved.

The role of targeted therapy in the management of patients with AML.

PubMed

Perl, Alexander E

2017-12-08

Drug therapy for acute myeloid leukemia (AML) is finally undergoing major changes in 2017. This is due to the US Food and Drug Administration's approval of several new, targeted agents (midostaurin, enasidenib, and gemtuzumab ozogamicin). Paired with the recent approval of a novel liposomal formulation of daunorubicin/cytarabine (CPX-351/Vyxeos), the standard of care is changing rapidly in AML for subgroups. This review will focus on currently approved agents and promising novel agents in development and will highlight controversial areas in targeted treatment. © 2016 by The American Society of Hematology. All rights reserved.

The MATISSE study: a randomised trial of group art therapy for people with schizophrenia

PubMed Central

2010-01-01

Background Art Therapy has been promoted as a means of helping people who may find it difficult to express themselves verbally engage in psychological treatment. Group Art Therapy has been widely used as an adjunctive treatment for people with schizophrenia but there have been few attempts to examine its effects and cost effectiveness has not been examined. The MATISSE study aims to evaluate the clinical and cost effectiveness of group Art Therapy for people with schizophrenia. Method/Design The MATISSE study is a three-arm, parallel group, pragmatic, randomised, controlled trial of referral to group Art Therapy plus standard care, referral to an attention control 'activity' group plus standard care, or standard care alone. Study participants were recruited from inpatient and community-based mental health and social care services at four centres in England and Northern Ireland. Participants were aged over 18 years with a clinical diagnosis of schizophrenia, confirmed by an examination of case notes using operationalised criteria. Participants were then randomised via an independent and remote telephone randomisation service using permuted stacked blocks, stratified by site. Art Therapy and activity groups were made available to participants once a week for up to 12 months. Outcome measures were assessed by researchers masked to allocation status at 12 and 24 months after randomisation. Participants and care givers were aware which arm of the trial participants were allocated to. The primary outcomes for the study are global functioning (measured using the Global Assessment of Functioning scale) and mental health symptoms (measured using the Positive and Negative Syndrome Scale) assessed at 24 months. Secondary outcomes were assessed at 12 and 24 months and comprise levels of group attendance, social function, satisfaction with care, mental wellbeing, and costs. Discussion We believe that this is the first large scale pragmatic trial of Art Therapy for people with schizophrenia. Trial registration Current Controlled Trials ISRCTN46150447 PMID:20799930

The Emergence of Precision Urologic Oncology: A Collaborative Review on Biomarker-driven Therapeutics.

PubMed

Barbieri, Christopher E; Chinnaiyan, Arul M; Lerner, Seth P; Swanton, Charles; Rubin, Mark A

2017-02-01

Biomarker-driven cancer therapy, also referred to as precision oncology, has received increasing attention for its promise of improving patient outcomes by defining subsets of patients more likely to respond to various therapies. In this collaborative review article, we examine recent literature regarding biomarker-driven therapeutics in urologic oncology, to better define the state of the field, explore the current evidence supporting utility of this approach, and gauge potential for the future. We reviewed relevant literature, with a particular focus on recent studies about targeted therapy, predictors of response, and biomarker development. The recent advances in molecular profiling have led to a rapid expansion of potential biomarkers and predictive information for patients with urologic malignancies. Across disease states, distinct molecular subtypes of cancers have been identified, with the potential to inform choices of management strategy. Biomarkers predicting response to standard therapies (such as platinum-based chemotherapy) are emerging. In several malignancies (particularly renal cell carcinoma and castration-resistant prostate cancer), targeted therapy against commonly altered signaling pathways has emerged as standard of care. Finally, targeted therapy against alterations present in rare patients (less than 2%) across diseases has the potential to drastically alter patterns of care and choices of therapeutic options. Precision medicine has the highest potential to impact the care of patients. Prospective studies in the setting of clinical trials and standard of care therapy will help define reliable predictive biomarkers and new therapeutic targets leading to real improvement in patient outcomes. Precision oncology uses molecular information (DNA and RNA) from the individual and the tumor to match the right patient with the right treatment. Tremendous strides have been made in defining the molecular underpinnings of urologic malignancies and understanding how these predict response to treatment-this represents the future of urologic oncology. Copyright © 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.

The Emergence of Precision Urologic Oncology: A Collaborative Review on Biomarker-driven Therapeutics

PubMed Central

Barbieri, Christopher E.; Chinnaiyan, Arul M.; Lerner, Seth P.; Swanton, Charles; Rubin, Mark A.

2016-01-01

Context Biomarker-driven cancer therapy, also referred to as precision oncology, has received increasing attention for its promise of improving patient outcomes by defining subsets of patients more likely to respond to various therapies. Objective In this collaborative review article, we examine recent literature regarding biomarker-driven therapeutics in urologic oncology, to better define the state of the field, explore the current evidence supporting utility of this approach, and gauge potential for the future. Evidence acquisition We reviewed relevant literature, with a particular focus on recent studies about targeted therapy, predictors of response, and biomarker development. Evidence synthesis The recent advances in molecular profiling have led to a rapid expansion of potential biomarkers and predictive information for patients with urologic malignancies. Across disease states, distinct molecular subtypes of cancers have been identified, with the potential to inform choices of management strategy. Biomarkers predicting response to standard therapies (such as platinum-based chemotherapy) are emerging. In several malignancies (particularly renal cell carcinoma and castration-resistant prostate cancer), targeted therapy against commonly altered signaling pathways has emerged as standard of care. Finally, targeted therapy against alterations present in rare patients (less than 2%) across diseases has the potential to drastically alter patterns of care and choices of therapeutic options. Conclusions Precision medicine has the highest potential to impact the care of patients. Prospective studies in the setting of clinical trials and standard of care therapy will help define reliable predictive biomarkers and new therapeutic targets leading to real improvement in patient outcomes. Patient summary Precision oncology uses molecular information (DNA and RNA) from the individual and the tumor to match the right patient with the right treatment. Tremendous strides have been made in defining the molecular underpinnings of urologic malignancies and understanding how these predict response to treatment—this represents the future of urologic oncology. PMID:27567210

Dawn of Aurora kinase inhibitors as anticancer drugs.

PubMed

Doggrell, Sheila A

2004-09-01

With the current standard chemotherapy regimens only approximately 25% of acute myelogenous leukaemia (AML) patients survive > 5 years. Aurora kinases are overexpressed in many human cancers. VX-680 inhibited Aurora-A, -B, -C and the FMS-like tyrosine kinase-3 with apparent inhibitory constants of 0.6, 18, 4.6 and 30 nM, respectively. In primary leukaemia cells from patients with AML, which were refractory to standard therapies, VX-680 inhibited colony formation. In nude mice, VX-680 markedly reduced human AML tumours. The development of VX-680 for use in AML should continue.

Emerging Therapies for Stage III Non-Small Cell Lung Cancer: Stereotactic Body Radiation Therapy and Immunotherapy.

PubMed

Kumar, Sameera S; Higgins, Kristin A; McGarry, Ronald C

2017-01-01

The current standard of care for locally advanced non-small cell lung cancer (NSCLC) includes radiation, chemotherapy, and surgery in certain individualized cases. In unresectable NSCLC, chemoradiation has been the standard of care for the past three decades. Local and distant failure remains high in this group of patients, so dose escalation has been studied in both single institution and national clinical trials. Though initial studies showed a benefit to dose escalation, phase III studies examining dose escalation using standard fractionation or hyperfractionation have failed to show a benefit. Over the last 17 years, stereotactic body radiation therapy (SBRT) has shown a high degree of safety and local control for stage I lung cancers and other localized malignancies. More recently, phase I/II studies using SBRT for dose escalation after conventional chemoradiation in locally advanced NSCLC have been promising with good apparent safety. Immunotherapy also offers opportunities to address distant disease and preclinical data suggest immunotherapy in tandem with SBRT may be a rational way to induce an "abscopal effect" although there are little clinical data as yet. By building on the proven concept of conventional chemoradiation for patients with locally advanced NSCLC with a subsequent radiation dose intensification to residual disease with SBRT concurrent with immunotherapy, we hope address the issues of metastatic and local failures. This "quadmodality" approach is still in its infancy but appears to be a safe and rational approach to the improving the outcome of NSCLC therapy.

The effect of cone beam CT (CBCT) on therapeutic decision-making in endodontics.

PubMed

Mota de Almeida, F J; Knutsson, K; Flygare, L

2014-01-01

The aim was to assess to what extent cone beam CT (CBCT) used in accordance with current European Commission guidelines in a normal clinical setting has an impact on therapeutic decisions in a population referred for endodontic problems. The study includes data of consecutively examined patients collected from October 2011 to December 2012. From 2 different endodontic specialist clinics, 57 patients were referred for a CBCT examination using criteria in accordance with current European guidelines. The CBCT examinations were performed using similar equipment and standardized among clinics. After a thorough clinical examination, but before CBCT, the examiner made a preliminary therapy plan which was recorded. After the CBCT examination, the same examiner made a new therapy plan. Therapy plans both before and after the CBCT examination were plotted for 53 patients and 81 teeth. As four patients had incomplete protocols, they were not included in the final analysis. 4% of the patients referred to endodontic clinics during the study period were examined with CBCT. The most frequent reason for referral to CBCT examination was to differentiate pathology from normal anatomy, this was the case in 24 patients (45% of the cases). The primary outcome was therapy plan changes that could be attributed to CBCT examination. There were changes in 28 patients (53%). CBCT has a significant impact on therapeutic decision efficacy in endodontics when used in concordance with the current European Commission guidelines.

Controversies in breast cancer: adjuvant and neoadjuvant therapy.

PubMed

Montemurro, Filippo; Redana, Stefania; Valabrega, Giorgio; Aglietta, Massimo

2005-06-01

Initial randomised studies of chemotherapy and endocrine therapy showed that systemic treatments had a substantial impact on the survival of women with early breast cancer. The original assumption was that the efficacy of these treatments was limited to those patients presenting with more adverse prognostic features. Subsequently, meta-analyses of randomised trials revealed that the benefits of chemotherapy and endocrine therapy are not mutually exclusive and extend to all the prognostic subgroups. However, the absolute benefit varies according to baseline characteristics such as tumour stage and other biological factors. Over the last 10 years, considerable progress has been made with the introduction of new drugs into the adjuvant and neoadjuvant treatment of women with breast cancer. Taxanes and third-generation aromatase inhibitors are providing proof of additional benefits compared with standard reference treatments. In parallel, research on the biology of breast cancer is establishing novel prognostic and predictive factors, which may allow better treatment tailoring. Currently, however, women with early breast cancer and their doctors face the difficult task of making therapeutic decisions often based on early results from positive studies. In a disease where follow up is crucial to fully assess the benefit and long-term toxicities of an intervention, current knowledge leaves unanswered questions that generate debate and controversy. This review will summarise recent results from randomised trials of adjuvant and neoadjuvant therapy in women with early breast cancer and focus on the current controversies.

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

Revision of the Competency Standards for Occupational Therapy Driver Assessors: An overview of the evidence for the inclusion of cognitive and perceptual assessments within fitness-to-drive evaluations.

PubMed

Fields, Sally M; Unsworth, Carolyn A

2017-08-01

Determination of fitness-to-drive after illness or injury is a complex process typically requiring a comprehensive driving assessment, including off-road and on-road assessment components. The competency standards for occupational therapy driver assessors (Victoria, Australia) define the requirements for performance of a comprehensive driving assessment, and we are currently revising these. Assessment of cognitive and perceptual skills forms an important part of the off-road assessment. The aim of this systematic review of systematic reviews (known as an overview) is to identify what evidence exists for including assessment of cognitive and perceptual skills within fitness-to-drive evaluations to inform revision of the competency standards. Five electronic databases (MEDLINE, CINAHL, PsycINFO, The Cochrane Library, OT Seeker) were systematically searched. Systematic review articles were appraised by two authors for eligibility. Methodological quality was independently assessed using the AMSTAR tool. Narrative analysis was conducted to summarise the content of eligible reviews. A total of 1228 results were retrieved. Fourteen reviews met the inclusion criteria. Reviews indicated that the components of cognition and perception most frequently identified as being predictive of fitness-to-drive were executive function (n = 13), processing speed (n = 12), visuospatial skills, attention, memory and mental flexibility (n = 11). Components less indicative were perception, concentration (n = 10), praxis (n = 9), language (n = 7) and neglect (n = 6). This overview of systematic reviews supports the inclusion of assessment of a range of cognitive and perceptual skills as key elements in a comprehensive driver assessment and therefore should be included in the revised competency standards for occupational therapy driver assessors. © 2017 Occupational Therapy Australia.

Management of Primary Adrenal Insufficiency: Review of Current Clinical Practice in a Developed and a Developing Country.

PubMed

Khan, Uzma; Lakhani, Om J

2017-01-01

Treatment of primary adrenal insufficiency (PAI) requires lifelong hormone replacement with glucocorticoids (GCs) and mineralocorticoids. Impaired quality of life and increased standardized mortality ratio in these patients emphasize the importance of tailoring therapy to individual needs. Role of education is paramount in improving patient compliance and in anticipating and preventing adrenal crises. Although discovery of synthetic GCs was a major breakthrough in treatment of patients with this life-threatening condition, management of PAI continues to be challenging. The obstacles for clinicians appear to vary widely across the globe. While optimization and individualization of therapy after diagnosis of PAI remain the main challenges for clinicians in the developed world, doctors in a developing country face problems at almost every stage from the diagnosis to the treatment and follow-up of these patients; cost of therapy, lack of resources, and funding are the main hindrances. Adherence to therapy and patient education are found to be common issues in most parts of the world. This commentary highlights the challenges from both developed and developing country's perspective in treating PAI; it also provides an update on current management scenario and future treatment options.

Current Approaches and Challenges for Monitoring Treatment Response in Colon and Rectal Cancer

PubMed Central

McKeown, Elizabeth; Nelson, Daniel W.; Johnson, Eric K.; Maykel, Justin A.; Stojadinovic, Alexander; Nissan, Aviram; Avital, Itzhak; Brücher, Björn LDM; Steele, Scott R.

2014-01-01

Introduction: With the advent of multidisciplinary and multimodality approaches to the management of colorectal cancer patients, there is an increasing need to define how we monitor response to novel therapies in these patients. Several factors ranging from the type of therapy used to the intrinsic biology of the tumor play a role in tumor response. All of these can aid in determining the ideal course of treatment, and may fluctuate over time, pending down-staging or progression of disease. Therefore, monitoring how disease responds to therapy requires standardization in order to ultimately optimize patient outcomes. Unfortunately, how best to do this remains a topic of debate among oncologists, pathologists, and colorectal surgeons. There may not be one single best approach. The goal of the present article is to shed some light on current approaches and challenges to monitoring treatment response for colorectal cancer. Methods: A literature search was conducted utilizing PubMed and the OVID library. Key-word combinations included colorectal cancer metastases, neoadjuvant therapy, rectal cancer, imaging modalities, CEA, down-staging, tumor response, and biomarkers. Directed searches of the embedded references from the primary articles were also performed in selected circumstances. Results: Pathologic examination of the post-treatment surgical specimen is the gold standard for monitoring response to therapy. Endoscopy is useful for evaluating local recurrence, but not in assessing tumor response outside of the limited information gained by direct examination of intra-lumenal lesions. Imaging is used to monitor tumors throughout the body for response, with CT, PET, and MRI employed in different circumstances. Overall, each has been validated in the monitoring of patients with colorectal cancer and residual tumors. Conclusion: Although there is no imaging or serum test to precisely correlate with a tumor's response to chemo- or radiation therapy, these modalities, when used in combination, can aid in allowing clinicians to adjust medical therapy, pursue operative intervention, or (in select cases) identify complete responders. Improvements are needed, however, as advances across multiple modalities could allow appropriate selection of patients for a close surveillance regimen in the absence of operative intervention. PMID:24396496

Recent controversies on comparative effectiveness research investigations: Challenges, opportunities, and pitfalls.

PubMed

Kirpalani, Haresh; Truog, William E; D'Angio, Carl T; Cotten, Michael

2016-10-01

The purpose of comparative effectiveness research (CER) is to improve health outcomes by developing and disseminating evidence-based information about which currently available interventions and practices are most effective for patients. Randomized Controlled Trials (RCT) are the hallmark of scientific proof, and have been used to compare interventions used in variable ways by different clinicians (comparative effectiveness RCTs, CER-RCTs). But such CER-RCTs have at times generated controversy. Usually the background for the CER-RCT is a range of "standard therapy" or "standard of care." This may have been adopted on observational data alone, or pilot data. At times, such prior data may derive from populations that differ from the population in which the widely variable standard approach is being applied. We believe that controversies related to these CER-RCTs result from confusing "accepted" therapies and "rigorously evaluated therapies." We first define evidence-based medicine and consider how well neonatology conforms to that definition. We then contrast the approach of testing new therapies and those already existing and widely adopted, as in CER-RCTs. We next examine a central challenge in incorporating the control arm within CER-RCTs and aspects of the "titrated" trial. We finally briefly consider some ethical issues that have arisen, and discuss the wide range of neonatology practices that could be tested by CER-RCTs or alternative CER-based strategies that might inform practice. Throughout, we emphasize the lack of awareness of the lay community, and indeed many researchers or commentators, in appreciating the wide variation of standard of care. There is a corresponding need to identify the best uses of available resources that will lead to the best outcomes for our patients. We conclude that CER-RCTs are an essential methodology in modern neonatology to address many unanswered questions and test unproven therapies in newborn care. Copyright © 2016 Elsevier Inc. All rights reserved.

Zinc as an adjunct treatment for reducing case fatality due to clinical severe infection in young infants: study protocol for a randomized controlled trial.

PubMed

Wadhwa, Nitya; Basnet, Sudha; Natchu, Uma Chandra Mouli; Shrestha, Laxman P; Bhatnagar, Shinjini; Sommerfelt, Halvor; Strand, Tor A; Ramji, Siddarth; Aggarwal, K C; Chellani, Harish; Govil, Anuradha; Jajoo, Mamta; Mathur, N B; Bhatt, Meenakshi; Mohta, Anup; Ansari, Imran; Basnet, Srijana; Chapagain, Ram H; Shah, Ganesh P; Shrestha, Binod M

2017-07-10

An estimated 2.7 of the 5.9 million deaths in children under 5 years of age occur in the neonatal period. Severe infections contribute to almost a quarter of these deaths. Mortality due to severe infections in developing country settings is substantial despite antibiotic therapy. Effective interventions that can be added to standard therapy for severe infections are required to reduce case fatality. This is a double-blind randomized placebo-controlled parallel group superiority trial to investigate the effect of zinc administered orally as an adjunct to standard therapy to infants aged 3 days up to 2 months (59 days) hospitalized with clinical severe infection, that will be undertaken in seven hospitals in Delhi, India and Kathmandu, Nepal. In a 1:1 ratio, we will randomly assign young infants to receive 10 mg of elemental zinc or placebo orally in addition to the standard therapy for a total of 14 days. The primary outcomes hospital case fatality, which is death due to any cause and at any time after enrolment while hospitalized for the illness episode, and extended case fatality, which encompasses the period until 12 weeks after enrolment. A previous study showed a beneficial effect of zinc in reducing the risk of treatment failure, as well as a non-significant effect on case fatality. This study was not powered to detect an effect on case fatality, which this current study is. If the results are consistent with this earlier trial, we would have provided strong evidence for recommending zinc as an adjunct to standard therapy for clinical severe infection in young infants. Universal Trial Number: U1111-1187-6479, Clinical Trials Registry - India: CTRI/2017/02/007966 : Registered on February 27, 2017.

Ilaj bil hijamah (cupping therapy) in the Unani system of medicine: anecdotal practice to evidence based therapy.

PubMed

Abbas Zaidi, S M; Jameel, S S; Jafri, Kehkashan; Khan, Shariq A; Ahmad, Ehsan

2016-08-01

Cupping (Hijamah) therapy is very well documented as a result of several thousand years of clinical experiences in Unani medicine. In this procedure, suction is created by various means either with or without bloodletting. Though this therapy is being widely practiced across the globe for treating many chronic and intractable ailments but many reports reveal its unscientific and improper practices which results in many complications. Therefore to develop standard operative procedures and to propose protocols of cupping therapy in various diseases is the need of hour. A thorough literature review of relevant journals and textbooks was performed to gather the maximum available data on cupping therapy. This paper seeks to introduce the general concepts of cupping therapy in Unani medicine and other traditional systems of medicine, shortcomings and limitations of the currently published studies and suggest ways to improve these technical/methodological flaws. In addition, the authors have also attempted to provide the cupping related materials, hypotheses, observations which will provide the researchers the base for evaluating their usefulness in future clinical trials.

Reducing rectal injury in men receiving prostate cancer radiation therapy: current perspectives

PubMed Central

Serrano, Nicholas A; Kalman, Noah S; Anscher, Mitchell S

2017-01-01

Dose escalation is now the standard of care for the treatment of prostate cancer with radiation therapy. However, the rectum tends to be the dose-limiting structure when treating prostate cancer, given its close proximity. Early and late toxicities can occur when the rectum receives large doses of radiation therapy. New technologies allow for prevention of these toxicities. In this review, we examine the evidence that supports various dose constraints employed to prevent these rectal injuries from occurring. We also examine the use of intensity-modulated radiation therapy and how this compares to older radiation therapy techniques that allow for further sparing of the rectum during a radiation therapy course. We then review the literature on endorectal balloons and the effects of their daily use throughout a radiation therapy course. Tissue spacers are now being investigated in greater detail; these devices are injected into the rectoprostatic fascia to physically increase the distance between the prostate and the anterior rectal wall. Last, we review the use of systemic drugs, specifically statin medications and antihypertensives, as well as their impact on rectal toxicity. PMID:28814898

Emerging therapies for Clostridium difficile infections.

PubMed

McFarland, Lynne V

2011-09-01

Clostridium difficile infection (CDI) is the leading identifiable gastrointestinal disease in healthcare institutions, but the response rates to the two standard therapies for CDI are declining and so innovative therapies are being developed for CDI. The purpose of this paper is to review the data on the efficacy and safety of emerging therapies for CDI and assess their potential for effectiveness based on the clinical phase of development and marketing challenges. Emerging therapies for CDI are reviewed including new antibiotics, peptides, immune regulators, probiotics and toxin binders. PubMed, Medline and Google Scholar and online clinical trial registers are searched from 1976 to 2010 for articles unrestricted by language. Secondary searches by author, manufacturing companies and FDA websites are also performed. Of the emerging therapies for CDI, several may ultimately reduce the incidence of CDI and the economic burden of this disease on the healthcare system. Several emerging treatments (fidaxomicin, rifaximin and mAbs) show the most promise, although only one is currently being actively developed. Use of other clostridial strains, probiotic strains and immune enhancers have great potential as therapies, but require further development.

Apixaban Versus Warfarin for Mechanical Heart Valve Thromboprophylaxis in a Swine Aortic Heterotopic Valve Model.

PubMed

Lester, Patrick A; Coleman, Dawn M; Diaz, Jose A; Jackson, Tatum O; Hawley, Angela E; Mathues, Angela R; Grant, Brandon T; Knabb, Robert M; Ramacciotti, Eduardo; Frost, Charles E; Song, Yan; Wakefield, Thomas W; Myers, Daniel D

2017-05-01

Warfarin is the current standard for oral anticoagulation therapy in patients with mechanical heart valves, yet optimal therapy to maximize anticoagulation and minimize bleeding complications requires routine coagulation monitoring, possible dietary restrictions, and drug interaction monitoring. As alternatives to warfarin, oral direct acting factor Xa inhibitors are currently approved for the prophylaxis and treatment of venous thromboembolism and reduction of stroke and systemic embolization. However, no in vivo preclinical or clinical studies have been performed directly comparing oral factor Xa inhibitors such as apixaban to warfarin, the current standard of therapy. A well-documented heterotopic aortic valve porcine model was used to test the hypothesis that apixaban has comparable efficacy to warfarin for thromboprophylaxis of mechanical heart valves. Sixteen swine were implanted with a bileaflet mechanical aortic valve that bypassed the ligated descending thoracic aorta. Animals were randomized to 4 groups: control (no anticoagulation; n=4), apixaban oral 1 mg/kg twice a day (n=5), warfarin oral 0.04 to 0.08 mg/kg daily (international normalized ratio 2-3; n=3), and apixaban infusion (n=4). Postmortem valve thrombus was measured 30 days post-surgery for control-oral groups and 14 days post-surgery for the apixaban infusion group. Control thrombus weight (mean) was significantly different (1422.9 mg) compared with apixaban oral (357.5 mg), warfarin (247.1 mg), and apixiban 14-day infusion (61.1 mg; P <0.05). Apixaban is a promising candidate and may be a useful alternative to warfarin for thromboprophylaxis of mechanical heart valves. Unlike warfarin, no adverse bleeding events were observed in any apixaban groups. © 2017 American Heart Association, Inc.

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

PubMed

Hamilton, Gregory S

2015-09-01

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

Mesenchymal stromal cell-based therapy: Regulatory and translational aspects in gastroenterology.

PubMed

Dothel, Giovanni; Raschi, Emanuel; Rimondini, Roberto; De Ponti, Fabrizio

2016-11-07

The past decade has witnessed an outstanding scientific production focused towards the possible clinical applications of mesenchymal stromal cells (MSCs) in autoimmune and chronic inflammatory diseases. This raised the need of novel standards to adequately address quality, efficacy and safety issues of this advanced therapy. The development of a streamlined regulation is currently hampered by the complexity of analyzing dynamic biological entities rather than chemicals. Although numerous pieces of evidence show efficacy in reducing intestinal inflammation, some inconsistencies between the mechanisms of action of rodent vs human MSCs suggest caution before assigning translational value to preclinical studies. Preliminary evidence from clinical trials showed efficacy of MSCs in the treatment of fistulizing Crohn's disease (CD), and preparations of heterologous MSCs for CD treatment are currently tested in ongoing clinical trials. However, safety issues, especially in long-term treatment, still require solid clinical data. In this regard, standardized guidelines for appropriate dosing and methods of infusion could enhance the likelihood to predict more accurately the number of responders and the duration of remission periods. In addition, elucidating MSC mechanisms of action could lead to novel and more reliable formulations such as those derived from the MSCs themselves ( e.g ., supernatants).

Diagnostics and Treatment of Hepatocellular Carcinoma in 2016: Standards and Developments.

PubMed

Trojan, Jörg; Zangos, Stephan; Schnitzbauer, Andreas A

2016-04-01

Hepatocellular carcinoma (HCC) is a frequent complication of liver cirrhosis. Worldwide, HCC is one of the most common cancers, with a rising incidence. A selective literature search was conducted, taking into account current studies, reviews, meta-analyses, and guidelines. The diagnosis is established either non-invasively by dynamic imaging, showing a typical contrast enhancement and wash-out, or histopathologically. Pathological diagnosis of HCC is recommended for all atypical nodules in patients with cirrhosis and for those in non-cirrhotic patients. Tumor therapy as well as treatment of the underlying chronic liver disease and/or preservation of liver function are important for the management of patients with HCC. Standard stage-adapted treatments are based on the widely applied Barcelona Clinic Liver Cancer staging system including liver resection and transplantation, interventional treatments such as thermal ablation and transarterial therapies, and systemic treatment with the tyrosine kinase inhibitor sorafenib. After failure of sorafenib, anti-angiogenic drugs, MET inhibitors, and immunotherapeutics are currently under advanced clinical investigation. Treatment of HCC is multidisciplinary and therefore requires a close cooperation between various disciplines such as hepatology, visceral surgery, radiology, and oncology to achieve the best outcome depending on the tumor stage and degree of liver function impairment.

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

Sarkaria, Jann N., E-mail: sarkaria.jann@mayo.edu; Galanis, Evanthia; Wu Wenting

Background: The mammalian target of rapamycin (mTOR) functions within the PI3K/Akt signaling pathway as a critical modulator of cell survival. On the basis of promising preclinical data, the safety and tolerability of therapy with the mTOR inhibitor RAD001 in combination with radiation (RT) and temozolomide (TMZ) was evaluated in this Phase I study. Methods and Materials: All patients received weekly oral RAD001 in combination with standard chemoradiotherapy, followed by RAD001 in combination with standard adjuvant temozolomide. RAD001 was dose escalated in cohorts of 6 patients. Dose-limiting toxicities were defined during RAD001 combination therapy with TMZ/RT. Results: Eighteen patients were enrolled,more » with a median follow-up of 8.4 months. Combined therapy was well tolerated at all dose levels, with 1 patient on each dose level experiencing a dose-limiting toxicity: Grade 3 fatigue, Grade 4 hematologic toxicity, and Grade 4 liver dysfunction. Throughout therapy, there were no Grade 5 events, 3 patients experienced Grade 4 toxicities, and 6 patients had Grade 3 toxicities attributable to treatment. On the basis of these results, the recommended Phase II dosage currently being tested is RAD001 70 mg/week in combination with standard chemoradiotherapy. Fluorodeoxyglucose (FDG) positron emission tomography scans also were obtained at baseline and after the second RAD001 dose before the initiation of TMZ/RT; the change in FDG uptake between scans was calculated for each patient. Fourteen patients had stable metabolic disease, and 4 patients had a partial metabolic response. Conclusions: RAD001 in combination with RT/TMZ and adjuvant TMZ was reasonably well tolerated. Changes in tumor metabolism can be detected by FDG positron emission tomography in a subset of patients within days of initiating RAD001 therapy.« less

Home noninvasive ventilation: what does the anesthesiologist need to know?

PubMed

Brown, Karen A; Bertolizio, Gianluca; Leone, Marisa; Dain, Steven L

2012-09-01

Treatment of chronic respiratory failure with noninvasive ventilation (NIV) is standard pediatric practice, and NIV systems are commonly used in the home setting. Although practice guidelines on the perioperative management of children supported with home NIV systems have yet to be published, increasingly these patients are referred for consultation regarding perioperative management. Just as knowledge of pharmacology underlies the safe prescription of medication, so too knowledge of biomedical design is necessary for the safe prescription of NIV therapy. The medical device design requirements developed by the Organization for International Standardization provide a framework to rationalize the safe prescription of NIV for hospitalized patients supported at home with NIV systems. This review article provides an overview of the indications for home NIV therapy, an overview of the medical devices currently available to deliver it, and a specific discussion of the management conundrums confronting anesthesiologists.

Misophonia: current perspectives

PubMed Central

Cavanna, Andrea E; Seri, Stefano

2015-01-01

Misophonia is characterized by a negative reaction to a sound with a specific pattern and meaning to a given individual. In this paper, we review the clinical features of this relatively common yet underinvestigated condition, with focus on co-occurring neurodevelopmental disorders. Currently available data on the putative pathophysiology of the condition can inform our understanding and guide the diagnostic process and treatment approach. Tinnitus retraining therapy and cognitive behavior therapy have been proposed as the most effective treatment strategies for reducing symptoms; however, current treatment algorithms should be validated in large population studies. At the present stage, competing paradigms see misophonia as a physiological state potentially inducible in any subject, an idiopathic condition (which can present with comorbid psychiatric disorders), or a symptomatic manifestation of an underlying psychiatric disorder. Agreement on the use of standardized diagnostic criteria would be an important step forward in terms of both clinical practice and scientific inquiry. Areas for future research include phenomenology, epidemiology, modulating factors, neurophysiological underpinnings, and treatment trials. PMID:26316758

Misophonia: current perspectives.

PubMed

Cavanna, Andrea E; Seri, Stefano

2015-01-01

Misophonia is characterized by a negative reaction to a sound with a specific pattern and meaning to a given individual. In this paper, we review the clinical features of this relatively common yet underinvestigated condition, with focus on co-occurring neurodevelopmental disorders. Currently available data on the putative pathophysiology of the condition can inform our understanding and guide the diagnostic process and treatment approach. Tinnitus retraining therapy and cognitive behavior therapy have been proposed as the most effective treatment strategies for reducing symptoms; however, current treatment algorithms should be validated in large population studies. At the present stage, competing paradigms see misophonia as a physiological state potentially inducible in any subject, an idiopathic condition (which can present with comorbid psychiatric disorders), or a symptomatic manifestation of an underlying psychiatric disorder. Agreement on the use of standardized diagnostic criteria would be an important step forward in terms of both clinical practice and scientific inquiry. Areas for future research include phenomenology, epidemiology, modulating factors, neurophysiological underpinnings, and treatment trials.

Music therapy as an adjunct to standard treatment for obsessive compulsive disorder and co-morbid anxiety and depression: A randomized clinical trial.

PubMed

Shiranibidabadi, Shahrzad; Mehryar, Amirhooshang

2015-09-15

Previous studies have highlighted the potential therapeutic benefits of music therapy as an adjunct to standard care, in a variety of psychiatric ailments including mood and anxiety disorders. However, the role of music in the treatment of obsessive-compulsive disorder (OCD) have not been investigated to date. In a single-center, parallel-group, randomized clinical trial (NCT02314195) 30 patients with OCD were randomly assigned to standard treatment (pharmacotherapy and cognitive-behavior therapy) plus 12 sessions of individual music therapy (n = 15) or standard treatment only (n = 15) for one month. Maudsley Obsessive-Compulsive Inventory, Beck Anxiety Inventory, and Beck Depression Inventory-Short Form were administered baseline and after one month. Thirty patients completed the study. Music therapy resulted in a greater decrease in total obsessive score (post-intervention score: music therapy+standard treatment: 12.4 ± 1.9 vs standard treatment only: 15.1 ± 1.7, p < 0.001, effect size = 56.7%). For subtypes, significant between-group differences were identified for checking (p = 0.004), and slowness (p = 0.019), but not for washing or responsibility. Music therapy was significantly more effective in reducing anxiety (post-intervention score: music therapy + standard treatment: 16.9 ± 7.4 vs standard treatment only: 22.9 ± 4.6, p < 0.001, effect size = 47.0%), and depressive symptoms (post-intervention score: music therapy + standard treatment: 10.8 ± 3.8 vs standard treatment: 17.1 ± 3.7, p < 0.001, effect size = 47.0%). Inclusion of a small sample size, lack of blinding due to the nature of the intervention, short duration of follow-up. In patients with OCD, music therapy, as an adjunct to standard care, seems to be effective in reducing obsessions, as well as co-morbid anxiety and depressive symptoms. Copyright © 2015. Published by Elsevier B.V.

Microfluidic Transduction Harnesses Mass Transport Principles to Enhance Gene Transfer Efficiency.

PubMed

Tran, Reginald; Myers, David R; Denning, Gabriela; Shields, Jordan E; Lytle, Allison M; Alrowais, Hommood; Qiu, Yongzhi; Sakurai, Yumiko; Li, William C; Brand, Oliver; Le Doux, Joseph M; Spencer, H Trent; Doering, Christopher B; Lam, Wilbur A

2017-10-04

Ex vivo gene therapy using lentiviral vectors (LVs) is a proven approach to treat and potentially cure many hematologic disorders and malignancies but remains stymied by cumbersome, cost-prohibitive, and scale-limited production processes that cannot meet the demands of current clinical protocols for widespread clinical utilization. However, limitations in LV manufacture coupled with inefficient transduction protocols requiring significant excess amounts of vector currently limit widespread implementation. Herein, we describe a microfluidic, mass transport-based approach that overcomes the diffusion limitations of current transduction platforms to enhance LV gene transfer kinetics and efficiency. This novel ex vivo LV transduction platform is flexible in design, easy to use, scalable, and compatible with standard cell transduction reagents and LV preparations. Using hematopoietic cell lines, primary human T cells, primary hematopoietic stem and progenitor cells (HSPCs) of both murine (Sca-1 + ) and human (CD34 + ) origin, microfluidic transduction using clinically processed LVs occurs up to 5-fold faster and requires as little as one-twentieth of LV. As an in vivo validation of the microfluidic-based transduction technology, HSPC gene therapy was performed in hemophilia A mice using limiting amounts of LV. Compared to the standard static well-based transduction protocols, only animals transplanted with microfluidic-transduced cells displayed clotting levels restored to normal. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Adoptive Cell Therapies for Glioblastoma

PubMed Central

Bielamowicz, Kevin; Khawja, Shumaila; Ahmed, Nabil

2013-01-01

Glioblastoma (GBM) is the most common and most aggressive primary brain malignancy and, as it stands, is virtually incurable. With the current standard of care, maximum feasible surgical resection followed by radical radiotherapy and adjuvant temozolomide, survival rates are at a median of 14.6 months from diagnosis in molecularly unselected patients (1). Collectively, the current knowledge suggests that the continued tumor growth and survival is in part due to failure to mount an effective immune response. While this tolerance is subtended by the tumor being utterly “self,” it is to a great extent due to local and systemic immune compromise mediated by the tumor. Different cell modalities including lymphokine-activated killer cells, natural killer cells, cytotoxic T lymphocytes, and transgenic chimeric antigen receptor or αβ T cell receptor grafted T cells are being explored to recover and or redirect the specificity of the cellular arm of the immune system toward the tumor complex. Promising phase I/II trials of such modalities have shown early indications of potential efficacy while maintaining a favorable toxicity profile. Efficacy will need to be formally tested in phase II/III clinical trials. Given the high morbidity and mortality of GBM, it is imperative to further investigate and possibly integrate such novel cell-based therapies into the current standards-of-care and herein we collectively assess and critique the state-of-the-knowledge pertaining to these efforts. PMID:24273748

Adoptive cell therapies for glioblastoma.

PubMed

Bielamowicz, Kevin; Khawja, Shumaila; Ahmed, Nabil

2013-01-01

Glioblastoma (GBM) is the most common and most aggressive primary brain malignancy and, as it stands, is virtually incurable. With the current standard of care, maximum feasible surgical resection followed by radical radiotherapy and adjuvant temozolomide, survival rates are at a median of 14.6 months from diagnosis in molecularly unselected patients (1). Collectively, the current knowledge suggests that the continued tumor growth and survival is in part due to failure to mount an effective immune response. While this tolerance is subtended by the tumor being utterly "self," it is to a great extent due to local and systemic immune compromise mediated by the tumor. Different cell modalities including lymphokine-activated killer cells, natural killer cells, cytotoxic T lymphocytes, and transgenic chimeric antigen receptor or αβ T cell receptor grafted T cells are being explored to recover and or redirect the specificity of the cellular arm of the immune system toward the tumor complex. Promising phase I/II trials of such modalities have shown early indications of potential efficacy while maintaining a favorable toxicity profile. Efficacy will need to be formally tested in phase II/III clinical trials. Given the high morbidity and mortality of GBM, it is imperative to further investigate and possibly integrate such novel cell-based therapies into the current standards-of-care and herein we collectively assess and critique the state-of-the-knowledge pertaining to these efforts.

Workshop to address gaps in regulation of minimally manipulated autologous cell therapies for homologous use in Canada.

PubMed

Chisholm, Jolene; von Tigerstrom, Barbara; Bedford, Patrick; Fradette, Julie; Viswanathan, Sowmya

2017-12-01

In Canada, minimally manipulated autologous cell therapies for homologous use (MMAC-H) are either regulated under the practice of medicine, or as drugs or devices under the Food and Drugs Act, Food and Drug Regulations (F&DR) or Medical Device Regulations (MDR). Cells, Tissues and Organs (CTO) Regulations in Canada are restricted to minimally manipulated allogeneic products for homologous use. This leaves an important gap in the interpretation of existing regulations. The purposes of this workshop co-organized by the Stem Cell Network and the Centre for Commercialization of Regenerative Medicine (CCRM) were to discuss the current state of regulation of MMAC-H therapies in Canada and compare it with other regulatory jurisdictions, with the intent of providing specific policy recommendations to Health Canada. Participants came to a consensus on the need for well-defined common terminology between regulators and stakeholders, a common source of confusion and misinformation. A need for a harmonized national approach to oversight of facilities providing MMAC-H therapies based on existing standards, such as Canadian Standards Association (CSA), was also voiced. Facilities providing MMAC-H therapies should also participate in collection of long-term data to ensure patient safety and efficacy of therapies. Harmonization across provinces of the procedures and practices involving administration of MMAC-H would be preferred. Participants felt that devices used to process MMAC-H are adequately regulated under existing MDR. Overly prescriptive regulation will stifle innovation, whereas insufficient regulation might allow unsafe or ineffective therapies to be offered. Until a clear, balanced and explicit approach is articulated, regulatory uncertainty remains a barrier. Copyright © 2017 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Deconstructing hierarchies: Service users as co-teachers in occupational therapy education.

PubMed

Yalon-Chamovitz, Shira; Kraiem, Yoav; Gutman, Carolyn

2017-01-01

While occupational therapy currently tends to view itself as operating based on a client-centered, collaborative approach, studies often reflect a gap between rhetoric and practice. This work presents a new pedagogic standard which moves away from the medical model and toward a collaborative, client-centred approach. It functions to support a practice which embraces the respect for, and partnership with, people receiving services and replaces historic patterns which may strengthen the legitimacy of the professional and sustain clients' dependence. This pedagogy develops a therapeutic dialogue which draws from partnerships created in the classroom, where occupational therapy students engage in courses with a co-teacher service user, and examines how the collaboration with service users contributes to the training of occupational therapy students. Students and co-teachers can participate in the challenging experience of integrating theoretical knowledge with lived experience, thereby augmenting the development of a new and inclusive knowledge base.

Recent Advances in Targeted Therapy for Glioma.

PubMed

Lin, Lin; Cai, Jinquan; Jiang, Chuanlu

2017-01-01

Gliomas are the most common primary malignant brain tumors, which have a universally fatal outcome. Current standard treatment for glioma patients is surgical removal followed by radiotherapy and adjuvant chemotherapy. Due to therapeutic resistance and tumor recurrence, efforts are ongoing to identify the molecules that are fundamental to regulate the tumor progression and provide additional methods for individual treatment of glioma patients. By studying the initiation and maintenance of glioma, studies focused on the targets of tyrosine kinase receptors including EGFR, PDGFR and other crucial signal pathways such as PI3K/AKT and RAS/RAF/MAPK pathway. Furthermore, recent advances in targeting immunotherapy and stem cell therapy also brought numerous strategies to glioma treatment. This article reviewed the researches focused on the advanced strategies of various target therapies for improving the glioma treatment efficacy, and discussed the challenges and future directions for glioma therapy. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Music therapy research in the NICU: an updated meta-analysis.

PubMed

Standley, Jayne

2012-01-01

To provide an overview of developmental and medical benefits of music therapy for preterm infants. Meta-analysis. Empirical music studies with preterm infants in the neonatal intensive care unit (NICU). Evidence-based NICU music therapy (NICU -MT ) was highly beneficial with an overall large significant effect size (Cohen's d = 0.82). Effects because of music were consistently in a positive direction. Results of the current analysis replicated findings of a prior meta-analysis and included extended use of music.(1) Benefits were greatest for live music therapy (MT ) and for use early in the infant's NICU stay (birth weight <1,000 g, birth postmenstrual age <28 weeks). Results justify strong consideration for the inclusion of the following evidence-based NICU -MT protocols in best practice standards for NICU treatment of preterm infants: music listening for pacification, music reinforcement of sucking, and music pacification as the basis for multilayered, multimodal stimulation.

Monitoring therapeutic anticoagulation with low molecular weight heparins: is it useful or misleading?

PubMed

Hammerstingl, C

2008-10-01

Weight adapted low molecular weight heparin (LMWH) treatment is recommended as initial anticoagulant therapy of deep vein thrombosis, pulmonary embolism, in patients with myocardial ischemia or when oral anticoagulation (OAC) must be interrupted peri- operatively. Traditionally unfractioned heparin (UFH) was used as standard short acting anticoagulant, with the therapy monitored by frequent laboratory testing. Currently LMWH have broadly replaced UFH as first- choice anticoagulant due to more preferable pharmacokinetics and a better safety profile. Therapeutic anticoagulation with LMWH can be achieved by subcutaneous weight adapted application and measurement of anti-factor Xa- activity (anti-Xa) has been established as gold standard for LMWH- monitoring. However, since almost all LMWH dosing regimens have been developed empirically without laboratory monitoring, there is still a debate ongoing about the usefulness and impact of anti-Xa-testing. Data are lacking that prove a clear correlation between obtained levels of anti-Xa and the patients' clinical outcome. Newer methods have been developed aiming to determine a broader spectrum of LMWH depending anticoagulant activity. Even though there are some promising preliminary results, these alternative methods are not ready for routine clinical use yet. Nevertheless, current guidelines advise determination of anti-Xa in special patient populations with markedly altered LMWH metabolism or to exclude residual LMWH- activity before surgery at very high risk of bleeding. The aim of this article is to review critically the usefulness of anti- Xa guidance of LMWH- therapy and to give new perspectives on upcoming methods of LMWH- monitoring.

Oxidative stress in organophosphate poisoning: role of standard antidotal therapy.

PubMed

Vanova, Nela; Pejchal, Jaroslav; Herman, David; Dlabkova, Alzbeta; Jun, Daniel

2018-08-01

Despite the main mechanism of organophosphate (OP) toxicity through inhibition of acetylcholinesterase (AChE) being well known over the years, some chronic adverse health effects indicate the involvement of additional pathways. Oxidative stress is among the most intensively studied. Overstimulation of cholinergic and glutamatergic nervous system is followed by intensified generation of reactive species and oxidative damage in many tissues. In this review, the role of oxidative stress in pathophysiology of OP poisoning and the influence of commonly used medical interventions on its levels are discussed. Current standardized therapy of OP intoxications comprises live-saving administration of the anticholinergic drug atropine accompanied by oxime AChE reactivator and diazepam. The capability of these antidotes to ameliorate OP-induced oxidative stress varies between both therapeutic groups and individual medications within the drug class. Regarding oxidative stress, atropine does not seem to have a significant effect on oxidative stress parameters in OP poisoning. In a case of AChE reactivators, pro-oxidative and antioxidative properties could be found. It is assumed that the ability of oximes to trigger oxidative stress is rather associated with their chemical structure than reactivation efficacy. The data indicating the potency of diazepam in preventing OP-induced oxidative stress are not available. Based on current knowledge on the mechanism of OP-mediated oxidative stress, alternative approaches (including antioxidants or multifunctional drugs) in therapy of OP poisoning are under consideration. Copyright © 2018 John Wiley & Sons, Ltd.

Laser CO2 treatment for vulvar lymphedema secondary to gynecological cancer therapy: A report of two cases and review of the literature.

PubMed

Sopracordevole, Francesco; Mancioli, Francesca; Canzonieri, Vincenzo; Buttignol, Monica; Giorda, Giorgio; Ciavattini, Andrea

2015-04-01

Vulvar lymphedema is an uncommon and disabling side-effect of pelvic lymphadenectomy and pelvic radiotherapeutic treatment for invasive genital cancer. Lymphorrhea, a complication of lymphedema, may be extremely distressing for patients due to the requirement to wear sanitary towels and as the pain and loss of elasticity of the vulvar skin and mucosa can cause discomfort during coitus. Surgical treatments of lymphorrhea and vulvar lymphedema secondary to gynecological cancer treatments remain controversial and are not currently considered to be the standard therapy. The present study reports two cases of vulvar lymphedema complicated by vulvar lymphorrhea in females who had undergone treatment for cervical and endometrial cancer, respectively; a review of the literature is also included. In the two present cases, vulvar lymphedemas were refractory to standard treatments, including decongestive therapy, manual lymph drainage, elastic bandaging, low-stretch bandaging, exercises and skin care. Laser CO 2 excision and vaporization of the whole skin and mucosal tissue of the vulva was successfully performed to treat the lymphorrhea and improve quality of life. Thus, the present two cases indicated that laser CO 2 surgery may present an additional therapy for the treatment of genital lymphedema that is refractory to other treatments.

[Biologic therapy in idiopathic inflammatory myopathy].

PubMed

Selva-O'Callaghan, Albert; Ramos Casals, Manel; Grau Junyent, Josep M

2014-09-15

The aim of this article is to study the evidence-based knowledge related to the use of biological therapies in patients diagnosed with idiopathic inflammatory myopathy (dermatomyositis, polymyositis and inclusion body myositis). In this review the leading published studies related to the use of biological therapy in patients with myositis are analysed; mainly those with high methodological standards, that means randomized and controlled studies. Methodological drawbacks due to the rarity and heterogeneity of these complex diseases are also addressed. Up to now is not possible to ascertain the biologics as a recommended therapy in patients with myositis, at least based in the current evidence-based knowledge, although it can not be neglected as a therapeutic option in some clinical situations, taking into account the scarce of effective treatments in those patients, especially in refractory myositis. Future studies probably will help to better define the role of biological therapies in patients with idiopathic inflammatory myopathy. Copyright © 2013 Elsevier España, S.L.U. All rights reserved.

Nutraceuticals in Prostate Disease: The Urologist’s Role

PubMed Central

Curtis Nickel, J; Shoskes, Daniel; Roehrborn, Claus G; Moyad, Mark

2008-01-01

Interest in and use of complementary and alternative therapies, especially nutraceuticals, is high in prostate disease. These therapies have shown potential in benign prostatic hyperplasia (BPH), prostatitis, and prostate cancer. Some have produced results equal to or better than pharmaceuticals currently prescribed for BPH. In category III prostatitis, some nutraceuticals may offer relief to patients who get little from standard therapy. Because it is becoming apparent that inflammation may play a role in the progression of BPH and development of prostate cancer, nutraceuticals, which commonly have anti-inflammatory properties, may play a role. These therapies have also shown potential in prostate cancer treatment and prevention, especially those that also reduce cardiovascular events or risk. Nevertheless, uses of some nutraceuticals in prostate disease have had less desirable consequences, showing lack of efficacy, adulteration, and/or severe side effects or drug interactions. By ensuring that these therapies undergo careful study for effectiveness, quality, and safety, urologists can look forward to adding them to their evidence-based armamentarium for prostate disease. PMID:18836556

Passive antibody-mediated immunotherapy for the treatment of malignant gliomas.

PubMed

Mitra, Siddhartha; Li, Gordon; Harsh, Griffith R

2010-01-01

Despite advances in understanding the molecular mechanisms of brain cancer, the outcome of patients with malignant gliomas treated according to the current standard of care remains poor. Novel therapies are needed, and immunotherapy has emerged with great promise. The diffuse infiltration of malignant gliomas is a major challenge to effective treatment; immunotherapy has the advantage of accessing the entire brain with specificity for tumor cells. Therapeutic immune approaches include cytokine therapy, passive immunotherapy, and active immunotherapy. Cytokine therapy involves the administration of immunomodulatory cytokines to activate the immune system. Active immunotherapy is the generation or augmentation of an immune response, typically by vaccination against tumor antigens. Passive immunotherapy connotes either adoptive therapy, in which tumor-specific immune cells are expanded ex vivo and reintroduced into the patient, or passive antibody-mediated therapy. In this article, the authors discuss the preclinical and clinical studies that have used passive antibody-mediated immunotherapy, otherwise known as serotherapy, for the treatment of malignant gliomas.

Individual music therapy for depression: randomised controlled trial.

PubMed

Erkkilä, Jaakko; Punkanen, Marko; Fachner, Jörg; Ala-Ruona, Esa; Pöntiö, Inga; Tervaniemi, Mari; Vanhala, Mauno; Gold, Christian

2011-08-01

Music therapy has previously been found to be effective in the treatment of depression but the studies have been methodologically insufficient and lacking in clarity about the clinical model employed. Aims To determine the efficacy of music therapy added to standard care compared with standard care only in the treatment of depression among working-age people. Participants (n = 79) with an ICD-10 diagnosis of depression were randomised to receive individual music therapy plus standard care (20 bi-weekly sessions) or standard care only, and followed up at baseline, at 3 months (after intervention) and at 6 months. Clinical measures included depression, anxiety, general functioning, quality of life and alexithymia. ISRCTN84185937. Participants receiving music therapy plus standard care showed greater improvement than those receiving standard care only in depression symptoms (mean difference 4.65, 95% CI 0.59 to 8.70), anxiety symptoms (1.82, 95% CI 0.09 to 3.55) and general functioning (-4.58, 95% CI -8.93 to -0.24) at 3-month follow-up. The response rate was significantly higher for the music therapy plus standard care group than for the standard care only group (odds ratio 2.96, 95% CI 1.01 to 9.02). Individual music therapy combined with standard care is effective for depression among working-age people with depression. The results of this study along with the previous research indicate that music therapy with its specific qualities is a valuable enhancement to established treatment practices.

[The significance of fenofibrate in the therapy of atherogenic dyslipoproteinaemia].

PubMed

Kucera, M; Oravec, S; Ocadlík, I

2010-08-01

There are accepted the lipid levels goals in all world, which are needed to achievement in primary and secondary prevention. Despite efficacy of current standards of care (including achievement of LDL-C, blood pressure and blood sugar goals), patients with atherogenic dyslipidemia (DLP) (high TG levels, low HDL-C, high apolipoprotein B and small dense LDL-particles), which is common in patients with diabetes melitus (DM), metabolic syndrome or cardiovascular diseases (KVD), remain exposed to a high residual risk of major cardiovascular events and microvascular complications. Statin therapy does not adequately address vascular risk asociated with elevated triglycerides (TG) and low HDL-C levels. As ACCORD lipid trial last time shows, the addition of lipid-modifying activity of fenofibrate to statin therapy benefited only certain subgroups of patients at increased cardiometabolic risk.

Safety of the Combined Use of Praziquantel and Albendazole in the Treatment of Human Hydatid Disease

PubMed Central

Alvela-Suárez, Lucía; Velasco-Tirado, Virginia; Belhassen-Garcia, Moncef; Novo-Veleiro, Ignacio; Pardo-Lledías, Javier; Romero-Alegría, Angela; Pérez del Villar, Luis; Valverde-Merino, María Paz; Cordero-Sánchez, Miguel

2014-01-01

There is still no well-established consensus about the clinical management of hydatidosis. Currently, surgery continues to be the first therapeutic option, although treatment with anti-parasitic drugs is indicated as an adjuvant to surgery to decrease the number of relapses and hydatid cyst size. When surgery is not possible, medical treatment is indicated. Traditionally, albendazole was used in monotherapy as the standard treatment. However, combined therapy with albendazole plus praziquantel appears to improve anti-parasitic effectiveness. To date, no safety studies focusing on such combined therapy have been published for the treatment of hydatidosis. In this work, we analyze the adverse effects seen in 57 patients diagnosed with hydatidosis who were treated with praziquantel plus albendazole combined therapy between 2006 and 2010. PMID:24615131

Engineering Therapeutic T Cells: From Synthetic Biology to Clinical Trials.

PubMed

Esensten, Jonathan H; Bluestone, Jeffrey A; Lim, Wendell A

2017-01-24

Engineered T cells are currently in clinical trials to treat patients with cancer, solid organ transplants, and autoimmune diseases. However, the field is still in its infancy. The design, and manufacturing, of T cell therapies is not standardized and is performed mostly in academic settings by competing groups. Reliable methods to define dose and pharmacokinetics of T cell therapies need to be developed. As of mid-2016, there are no US Food and Drug Administration (FDA)-approved T cell therapeutics on the market, and FDA regulations are only slowly adapting to the new technologies. Further development of engineered T cell therapies requires advances in immunology, synthetic biology, manufacturing processes, and government regulation. In this review, we outline some of these challenges and discuss the contributions that pathologists can make to this emerging field.

The current status of neoadjuvant therapy for esophageal cancer.

PubMed

Lin, Daniel; Leichman, Lawrence

2014-01-01

Through the contribution of a very large number of single-arm phase II trials and many less randomized phase III trials, the standard of care for locally advanced esophageal cancer has evolved to either combination chemotherapy plus radiation or combination chemotherapy. In this review, we focus on the key findings of these studies and selected meta-analyses that have led to this evolution. We note differences in outcomes for adenocarcinomas of the esophagus when compared to squamous cell esophageal cancers. Despite progress in developing a consensus for therapy, the outcome for patients with locally advanced remains poor. We complete the review by noting newer areas of investigation seeking to provide targeted and more personalized therapy to patients with esophageal cancer. Copyright © 2014 Elsevier Inc. All rights reserved.

A Randomized Controlled Trial of 7-Day Intensive and Standard Weekly Cognitive Therapy for PTSD and Emotion-Focused Supportive Therapy

PubMed Central

Ehlers, Anke; Hackmann, Ann; Grey, Nick; Wild, Jennifer; Liness, Sheena; Albert, Idit; Deale, Alicia; Stott, Richard; Clark, David M.

2014-01-01

Objective Psychological treatments for posttraumatic stress disorder (PTSD) are usually delivered once or twice weekly over several months. It is unclear whether they can be successfully delivered over a shorter period of time. This clinical trial had two goals, (1) to investigate the acceptability and efficacy of a 7-day intensive version of cognitive therapy for PTSD, and (2) to investigate whether cognitive therapy has specific treatment effects by comparing intensive and standard weekly cognitive therapy with an equally credible alternative treatment. Method Patients with chronic PTSD (N=121) were randomly allocated to 7-day intensive or standard 3-month weekly cognitive therapy for PTSD, 3-month weekly emotion-focused supportive therapy, or a 14-week waitlist condition. Primary outcomes were PTSD symptoms and diagnosis as assessed by independent assessors and self-report. Secondary outcomes were disability, anxiety, depression, and quality of life. Measures were taken at initial assessment, 6 weeks and 14 weeks (post-treatment/wait). For groups receiving treatment, measures were also taken at 3 weeks, and follow-ups at 27 and 40 weeks after randomization. All analyses were intent-to-treat. Results At post-treatment/wait assessment, 73%, 77%, 43%, 7% of the intensive cognitive therapy, standard cognitive therapy, supportive therapy, and waitlist groups, respectively, had recovered from PTSD. All treatments were well tolerated and were superior to waitlist on all outcome measures, with the exception of no difference between supportive therapy and waitlist on quality of life. For primary outcomes, disability and general anxiety, intensive and standard cognitive therapy were superior to supportive therapy. Intensive cognitive therapy achieved faster symptom reduction and comparable overall outcomes to standard cognitive therapy. Conclusions Cognitive therapy for PTSD delivered intensively over little more than a week is as effective as cognitive therapy delivered over 3 months. Both had specific effects and were superior to supportive therapy. Intensive cognitive therapy for PTSD is a feasible and promising alternative to traditional weekly treatment. PMID:24480899

Standardizing of Pathology in Patients Receiving Neoadjuvant Chemotherapy.

PubMed

Bossuyt, Veerle; Symmans, W Fraser

2016-10-01

The use of neoadjuvant systemic therapy for the treatment of breast cancer patients is increasing. Pathologic response in the form of pathologic complete response (pCR) and grading systems of partial response, such as the residual cancer burden (RCB) system, gives valuable prognostic information for patients and is used as a primary endpoint in clinical trials. The breast cancer and pathology communities are responding with efforts to standardize pathology in patients receiving neoadjuvant chemotherapy. In this review, we summarize the challenges that postneoadjuvant systemic therapy surgical specimens pose and how pathologists and the multidisciplinary team can work together to optimize handling of these specimens. Multidisciplinary communication is essential. A single, standardized approach to macroscopic and microscopic pathologic examination makes it possible to provide reliable response information. This approach employs a map of tissue sections to correlate clinical, gross, microscopic, and imaging findings in order to report the presence of pCR (ypT0 ypN0 and ypT0/is ypN0) versus residual disease, the ypT and ypN stage using the current AJCC/UICC staging system, and the RCB.

Pharmacotherapy of Scleritis: Current Paradigms and Future Directions

PubMed Central

Beardsley, Robert M.; Suhler, Eric B.; Rosenbaum, James T.; Lin, Phoebe

2013-01-01

Introduction Scleritis is an inflammatory condition affecting the eye wall that may be associated with a number of systemic inflammatory diseases. Because scleritis can be refractory to standard treatment, knowledge of the body of available and emerging therapies is paramount and is reviewed here. Areas Covered This review focuses on both traditional and emerging therapies for non-infectious scleritis. We will cover the mechanisms of action and potential adverse effects of each of the treatment modalities. Additionally, a summary of the significant MEDLINE indexed literature under the subject heading “scleritis,” “treatment,” “immunomodulator” will be provided on each therapy, including commentary on appropriate use and relative contraindications. Lastly, novel treatments and potential drug candidates that are currently being evaluated in clinical trials with therapeutic potential will also be reviewed. Expert Opinion While oral non-steroidal anti-inflammatory drugs (NSAIDs) and oral corticosteroids are widely used, effective, first-line agents for inflammatory scleritis, refractory cases require anti-metabolites, T cell inhibitors, or biologic response modifiers. In particular, there is emerging evidence for the use of targeted biologic response modifiers, and potentially, for local drug delivery. PMID:23425055

Empiric therapy directed against MRSA in patients admitted to the intensive care unit does not improve outcomes in community-acquired pneumonia.

PubMed

Griffin, A T; Peyrani, P; Wiemken, T L; Ramirez, J A; Arnold, F W

2013-04-01

The Infectious Diseases Society of America has recommended empiric therapy active against methicillin-resistant Staphylococcus aureus (MRSA) for all community-acquired pneumonia (CAP) patients admitted to the intensive care unit (ICU). However, there is sparse data to support this recommendation. The objective of our study was to ascertain if such a practice improves outcomes. This study was a secondary, retrospective analysis of the Community-Acquired Pneumonia Organization (CAPO) international database on CAP. Outcomes in patients admitted to the ICU were compared according to empiric initiation of anti-MRSA therapy (vancomycin or linezolid) with standard ICU CAP therapy (MRSA therapy group) or standard therapy alone for ICU CAP (standard therapy group). A total of 621 patients were identified with ICU pneumonia, of whom 57 patients had been initiated empirically on vancomycin or linezolid (MRSA therapy group). Patients of the MRSA therapy group had more comorbidities and were more severely ill than those of the standard therapy group. However, there were no statistical differences between the MRSA therapy group and standard therapy group for the primary outcomes of in-hospital and 28-day mortality, length of stay and time to clinical stability. These findings suggest that empiric MRSA therapy in all ICU CAP patients may not improve outcomes and argue for clinician review of local epidemiologic trends on MRSA prevalence to ascertain the need for empiric MRSA coverage.

Cost-effectiveness evaluation of voriconazole versus liposomal amphotericin B as empirical therapy for febrile neutropenia in Australia.

PubMed

Al-Badriyeh, Daoud; Liew, Danny; Stewart, Kay; Kong, David C M

2009-01-01

A major randomized clinical trial, evaluating voriconazole versus liposomal amphotericin B (LAMB) as empirical therapy in febrile neutropenia, recommended voriconazole as a suitable alternative to LAMB. The current study sought to investigate the health economic impact of using voriconazole and LAMB for febrile neutropenia in Australia. A decision analytic model was constructed to capture downstream consequences of empirical antifungal therapy with each agent. The main outcomes were: success, breakthrough fungal infection, persistent baseline fungal infection, persistent fever, premature discontinuation and death. Underlying transition probabilities and treatment patterns were derived directly from trial data. Resource use was estimated using an expert panel. Cost inputs were obtained from the latest Australian representative published sources. The perspective adopted was that of the Australian hospital. Uncertainty and sensitivity analyses were undertaken via the Monte Carlo simulation. Compared with voriconazole, LAMB was associated with a net cost saving of AU$1422 (2.9%) per patient. A similar trend was observed with the cost per death prevented and successful treatment. LAMB dominated voriconazole as it resulted in higher efficacy and lower costs when compared with voriconazole. The results were most sensitive to the duration of therapy and the alternative therapy used post discontinuations. In uncertainty analysis, LAMB had 99.8% chance of costing less than voriconazole. In this study, which used the current standard five component endpoint to assess the impact of empirical antifungal therapy, LAMB was associated with cost savings relative to voriconazole.

Influence of gut microbiota and intestinal barrier on enterogenic infection after liver transplantation.

PubMed

Mu, Jingzhou; Chen, Qiuyu; Zhu, Liang; Wu, Yunhong; Liu, Suping; Zhao, Yufei; Ma, Tonghui

2018-04-27

Liver transplantation is currently a standard therapy for patients with end-stage liver diseases and hepatocellular carcinoma. Given that liver transplantation has undergone a thriving development in these decades, the survival rates after liver transplantation have markedly improved as a result of the critical advancement in surgical techniques, immunosuppressive therapies, and postoperative care. However, infection remains a fatal complication after liver transplantation surgery. In particular, enterogenic infection represents a major complication in liver transplant recipients. This article gives an overview of infection cases after liver transplantation and focuses on the discussion of enterogenic infection in terms of its pathophysiology, risk factor, outcome, and treatment.

Management of a new isolated metastasis during sunitinib treatment in renal cell carcinoma patients: a lesson from two cases.

PubMed

Shablak, Alaaeldin; O'Dwyer, Jackie; Hawkins, Robert; Board, Ruth

2011-01-01

Metastatic renal cell carcinoma (mRCC) is a difficult to treat malignancy and currently Sunitinib is a standard of care first-line therapy. A new metastasis during the treatment is considered a sign of drug failure and alternative therapeutic methods should be tried. Here, we report 2 cases of newly diagnosed isolated metastasis during Sunitinib treatment of mRCC patients. Our management plan included local palliative therapy to the lesion followed by recommencing of Sunitinib. This resulted in a good symptomatic relief locally as well as good overall control of the disease. Copyright © 2010 S. Karger AG, Basel.

Diverticular disease: A therapeutic overview

PubMed Central

Tursi, Antonio

2010-01-01

Formation of colonic diverticula, via herniation of the colonic wall, is responsible for the development of diverticulosis. When diverticulosis becomes symptomatic, it becomes diverticular disease. Diverticular disease is common in Western and industrialized countries, and it is associated with numerous abdominal symptoms (including pain, bloating, nausea, diarrhea, and constipation). Standard medical therapies with antibiotics are currently recommended for patients affected by diverticular disease. However, changing concepts on the pathophysiology of the disease suggest that diverticular disease may share many of the hallmarks of inflammatory bowel diseases. On this basis, the addition of therapies using mesalazine and probiotics may enhance treatment efficacy by shortening the course of the disease and preventing recurrences. PMID:21577292

[Evidence-based therapy for tendinopathy of the knee joint : Which forms of therapy are scientifically proven?

PubMed

Horstmann, H; Clausen, J D; Krettek, C; Weber-Spickschen, T S

2017-03-01

Tendinopathy in the region of the knee joint is a common pathological disorder. People active in sports, in particular, have a high probability of suffering from tendinopathy. Despite its high clinical relevance, the level of evidence of therapy options for tendinopathy in the knee region differs greatly. This review gives an overview of current evidence levels for therapy options in tendinopathy of the quadriceps, patellar and pes anserinus insertion tendons as well as of the distal iliotibial tract tendon. The treatment with platelet-rich plasma showed a significantly better outcome when used correctly and treatment with shock waves, operative treatment and sclerotherapy have also shown positive effects. Treatment with corticosteroid injections and with oral non-steroidal anti-inflammatory drugs (NSAID) showed positive short-term effects (follow-up ±4 weeks). No reasonable data are available for the treatment of tendinopathy in the knee region by acupuncture, fascial therapy or cryotherapy. The use of kinesio taping showed no significant relief from complaints compared with standard conservative treatment. The use of multimodal therapy without evidence is, therefore, particularly common in elite athletes.

Sequential therapy versus standard triple-drug therapy for Helicobacter pylori eradication: a randomized study.

PubMed

Nasa, Mukesh; Choksey, Ajay; Phadke, Aniruddha; Sawant, Prabha

2013-11-01

Antimicrobial resistance has decreased eradication rates for Helicobacter pylori infection worldwide. A sequential treatment schedule has been reported to be effective, but studies published to date were performed in Italy. We undertook this study to determine whether these results could be replicated in India. A randomized, open-labeled, prospective controlled trial comparing sequential vs. standard triple-drug therapy was carried out at Lokmanya Tilak Municipal General Hospital, Mumbai. Two hundred and thirty-one patients with dyspepsia were randomized to a 10-day sequential regimen (40 mg of pantoprazole, 1 g of amoxicillin, each administered twice daily for the first 5 days, followed by 40 mg of pantoprazole, 500 mg of clarithromycin, and 500 mg of tinidazole, each administered twice daily for the remaining 5 days) or to standard 14-day therapy (40 mg of pantoprazole, 500 mg of clarithromycin, and 1 g of amoxicillin, each administered twice daily). The eradication rate achieved with the sequential regimen was significantly greater than that obtained with the triple therapy. Per-protocol eradication rate of sequential therapy was 92.4% (95% CI 85.8-96.1%) vs. 81.8% (95% CI 73.9-87.8%) (p = 0.027) for standard drug therapy. Intention-to-treat eradication rates were 88.2% (95% CI 80.9-93.0%) vs. 79.1% (95% CI 71.1-85.4%), p = 0.029, respectively. The incidence of major and minor side effects between therapy groups was not significantly different (14.6% in the triple therapy group vs. 23.5% in sequential group, p = 0.12). Follow up was incomplete in 3.3% and 4.7% patients in standard and sequential therapy groups, respectively. Sequential therapy includes one additional antibiotic (tinidazole) that is not contained in standard therapy. Sequential therapy was significantly better than standard therapy for eradicating H. pylori infection.

Potential role for mammalian target of rapamycin inhibitors as first-line therapy in hormone receptor–positive advanced breast cancer

PubMed Central

Beck, J Thaddeus

2015-01-01

Despite advances in cytotoxic chemotherapy and targeted therapies, 5-year survival rates remain low for patients with advanced breast cancer at diagnosis. This highlights the limited effectiveness of current treatment options. An improved understanding of cellular functions associated with the development and progression of breast cancer has resulted in the creation of a number of novel targeted molecular therapies. However, more work is needed to improve outcomes, particularly in the first-line recurrent or metastatic hormone receptor–positive breast cancer setting. The phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (mTOR) pathway is a major intracellular signaling pathway that is often upregulated in breast cancer, and overactivation of this pathway has been associated with primary or developed resistance to endocrine treatment. Clinical data from the Phase III Breast Cancer Trials of Oral Everolimus-2 (BOLERO-2) study of the mTOR inhibitor everolimus combined with exemestane in hormone receptor–positive advanced breast cancer were very promising, highlighting the potential role of mTOR inhibitors in combination with endocrine therapies as a first-line treatment option for these patients. It is hoped that the use of mTOR inhibitors combined with current standard-of-care endocrine therapies, such as aromatase inhibitors, in the first-line advanced breast cancer setting may result in greater antitumor effects and also delay or reverse treatment resistance. PMID:26675495

Precision Oncology and Genomically Guided Radiation Therapy: A Report From the American Society for Radiation Oncology/American Association of Physicists in Medicine/National Cancer Institute Precision Medicine Conference.

PubMed

Hall, William A; Bergom, Carmen; Thompson, Reid F; Baschnagel, Andrew M; Vijayakumar, Srinivasan; Willers, Henning; Li, X Allen; Schultz, Christopher J; Wilson, George D; West, Catharine M L; Capala, Jacek; Coleman, C Norman; Torres-Roca, Javier F; Weidhaas, Joanne; Feng, Felix Y

2018-06-01

To summarize important talking points from a 2016 symposium focusing on real-world challenges to advancing precision medicine in radiation oncology, and to help radiation oncologists navigate the practical challenges of precision, radiation oncology. The American Society for Radiation Oncology, American Association of Physicists in Medicine, and National Cancer Institute cosponsored a meeting on precision medicine in radiation oncology. In June 2016 numerous scientists, clinicians, and physicists convened at the National Institutes of Health to discuss challenges and future directions toward personalized radiation therapy. Various breakout sessions were held to discuss particular components and approaches to the implementation of personalized radiation oncology. This article summarizes the genomically guided radiation therapy breakout session. A summary of existing genomic data enabling personalized radiation therapy, ongoing clinical trials, current challenges, and future directions was collected. The group attempted to provide both a current overview of data that radiation oncologists could use to personalize therapy, along with data that are anticipated in the coming years. It seems apparent from the provided review that a considerable opportunity exists to truly bring genomically guided radiation therapy into clinical reality. Genomically guided radiation therapy is a necessity that must be embraced in the coming years. Incorporating these data into treatment recommendations will provide radiation oncologists with a substantial opportunity to improve outcomes for numerous cancer patients. More research focused on this topic is needed to bring genomic signatures into routine standard of care. Published by Elsevier Inc.

Music therapy services for individuals with autism spectrum disorder: a survey of clinical practices and training needs.

PubMed

Kern, Petra; Rivera, Nicole R; Chandler, Alie; Humpal, Marcia

2013-01-01

Over the past decade, the definitions, diagnoses, prevalence rates, theories about the causes, evidence-based treatment options, and practice guidelines pertaining to Autism Spectrum Disorder (ASD) have undergone numerous changes. While several recent studies evaluate the effects of music therapy interventions for individuals with ASD, no current review reflects the latest music therapy practices and trends. The purpose of this study was to evaluate the status of music therapy practices for serving clients with ASD, the implementation of national ASD standards and guidelines, the awareness of recent developments, and training needs of music therapists. Professional members of the American Music Therapy Association who are working with individuals with ASD served as the sample for this national cross-sectional survey study (N = 328). A 45-item online questionnaire was designed and distributed through email and social media. Participants accessed the online survey through SurveyMonkey®. Findings suggest music therapy practices and services for individuals with ASD have shifted and now reflect a slightly higher percentage of caseload, a broader age range of clients, and a trend to serve clients in home and community settings. Most therapeutic processes align with recommended practices for ASD and incorporate several of the recognized evidence-based practices. Less understood or recognized are inclusion practices and latest developments in the field of ASD. Music therapists have a solid understanding of providing services for individuals with ASD, but would benefit from advanced online training and improved information dissemination to stay current with the rapidly changing aspects pertinent to this population. © 2013 by the American Music Therapy Association.

THE DEVELOPMENT OF BEHAVIOR DIMENSIONS FOR EMOTIONALLY DISTURBED CHILDREN--A STUDY OF RELEVANT INDICATORS FOR CLASSROOM TECHNIQUES, THERAPIES METHODS, AND PROGNOSIS. INTERIM REPORT.

ERIC Educational Resources Information Center

CROMWELL, RUE L.

FOUR INSTRUMENTS WERE DEVELOPED AND STANDARDIZED TO MEASURE EARLY EXPERIENCE, CURRENT BEHAVIOR, TREATMENT APPROACHES, AND PROGNOSIS OF EMOTIONALLY DISTURBED CHILDREN--THE RATING/RANKING SCALE OF CHILD BEHAVIOR (R/R SCALE), THE PARENT PRACTICES INVENTORY (PPI), THE SCALE ON PROCEDURES IN DEALING WITH CHILDREN (PDC), AND THE CHILD HISTORY CODE…

Current management of penetrating torso trauma: nontherapeutic is not good enough anymore.

PubMed

Ball, Chad G

2014-04-01

A highly organized approach to the evaluation and treatment of penetrating torso injuries based on regional anatomy provides rapid diagnostic and therapeutic consistency. It also minimizes delays in diagnosis, missed injuries and nontherapeutic laparotomies. This review discusses an optimal sequence of structured rapid assessments that allow the clinician to rapidly proceed to gold standard therapies with a minimal risk of associated morbidity.

The effect of cone beam CT (CBCT) on therapeutic decision-making in endodontics

PubMed Central

Knutsson, K; Flygare, L

2014-01-01

Objectives: The aim was to assess to what extent cone beam CT (CBCT) used in accordance with current European Commission guidelines in a normal clinical setting has an impact on therapeutic decisions in a population referred for endodontic problems. Methods: The study includes data of consecutively examined patients collected from October 2011 to December 2012. From 2 different endodontic specialist clinics, 57 patients were referred for a CBCT examination using criteria in accordance with current European guidelines. The CBCT examinations were performed using similar equipment and standardized among clinics. After a thorough clinical examination, but before CBCT, the examiner made a preliminary therapy plan which was recorded. After the CBCT examination, the same examiner made a new therapy plan. Therapy plans both before and after the CBCT examination were plotted for 53 patients and 81 teeth. As four patients had incomplete protocols, they were not included in the final analysis. Results: 4% of the patients referred to endodontic clinics during the study period were examined with CBCT. The most frequent reason for referral to CBCT examination was to differentiate pathology from normal anatomy, this was the case in 24 patients (45% of the cases). The primary outcome was therapy plan changes that could be attributed to CBCT examination. There were changes in 28 patients (53%). Conclusions: CBCT has a significant impact on therapeutic decision efficacy in endodontics when used in concordance with the current European Commission guidelines. PMID:24766060

Current role of hyperthermic intraperitoneal chemotherapy in the treatment of peritoneal carcinomatosis from colorectal cancer

PubMed Central

Rampone, Bernardino; Schiavone, Beniamino; Martino, Antonio; Confuorto, Giuseppe

2010-01-01

Peritoneal carcinomatosis is one of the most common routes of dissemination of colorectal cancer (CRC). It is encountered in 7% of patients at primary surgery, while it develops in about 4% to 19% of patients after curative surgery and in up to 44% of patients with recurrent CRC. Peritoneal involvement from colorectal malignancies has been considered traditionally as a manifestation of terminal disease, due to limited response to conventional surgical and chemotherapeutic treatments. In the past few years the introduction of cytoreductive surgery combined with hyperthermic intraperitoneal chemoperfusion has shown promising results in selected patients. Currently, the surgical management of peritoneal surface malignancies of colonic origin with this combined locoregional therapy has resulted in a significant improvement in survival of these patients. However, further controlled studies will help to standardize indications and the technique of this locoregional therapy in order to achieve an improvement of morbidity and mortality rates. PMID:20238394

[Precision Oncology and "Molecular Tumor Boards" - Concepts, Chances and Challenges].

PubMed

Holch, Julian Walter; Westphalen, Christoph Benedikt; Hiddemann, Wolfgang; Heinemann, Volker; Jung, Andreas; Metzeler, Klaus Hans

2017-11-01

Recent developments in genomics allow a more and more comprehensive genetic analysis of human malignancies, and have sparked hopes that this will contribute to the development of novel targeted, effective and well-tolerated therapies.While targeted therapies have improved the prognosis of many cancer patients with certain tumor types, "precision oncology" also brings along new challenges. Highly personalized treatment strategies require new strategies for clinical trials and translation into routine clinical practice. We review the current technical approaches for "universal genetic testing" in cancer, and potential pitfalls in the interpretation of such data. We then provide an overview of the available evidence supporting treatment strategies based on extended genetic analysis. Based on the available data, we conclude that "precision oncology" approaches that go beyond the current standard of care should be pursued within the framework of an interdisciplinary "molecular tumor board", and preferably within clinical trials. © Georg Thieme Verlag KG Stuttgart · New York.

Advances in the management of follicular lymphoma.

PubMed

Seiler, Till M; Hiddemann, Wolfgang

2012-11-01

Antibody-based therapy has revolutionized treatment strategies in follicular lymphoma. This review focuses on current standards and recent innovations in the management of the disease. Understanding the mechanism of action of antibodies led to the development of next generation CD20 antibodies, antibodies targeting other molecules and bispecific antibodies. With obinutuzumab, a promising next generation of CD20 antibodies has entered phase III of clinical trials. The bispecific T-cell engager blinatumomab combines targeted therapy with immunologic activation of T cells exerting cytotoxic activity on the target cells. Apart from antibodies, small molecules targeting key pathways in lymphoma have shown promising activity in vitro and are currently in clinical development. A wealth of new substances has entered various stages of clinical trials and has yet to show superiority over rituximab-based immunochemotherapy. Intelligent therapeutic regimens containing these drugs have to be developed. Large randomized trials comparing promising treatment options are urgently needed.

[Child sexual abuse. Epidemiology, clinical diagnostics, therapy, and prevention].

PubMed

Fegert, J M; Hoffmann, U; Spröber, N; Liebhardt, H

2013-02-01

The article provides an overview of the research on sexual abuse and the current political developments in Germany. First, the terminology of sexual child abuse is discussed, followed by the presentation of epidemiological data. The section on diagnostics and therapy shows that--because of mostly nonspecific indicators--the diagnosis of child sexual abuse is very difficult to define. Child sexual abuse is discussed as a traumatic experience for children and adolescents with different psychiatric and physical diseases. Current studies have shown that especially cognitive behavioral therapeutic-oriented approaches are effective in curing posttraumatic stress disorders. Based on the new German Child Protection Act, the focus lies on the clarification of confidentiality for medical professionals and their right to consulting services for child protection. In conclusion, guidelines and minimum standards for a child prevention and protection model are presented as well as institutional recommendations addressed to all institutions (also clinical) that take care of or treat children and adolescents.

Contemporary approach to stroke prevention in atrial fibrillation: Risks, benefits, and new options.

PubMed

Stock, Jonathan; Malm, Brian J

2018-04-04

Atrial fibrillation is a common diagnosis affecting nearly 3 million adults in the United States. Morbidity and mortality in these patients is driven largely by the associated increased risk of thromboembolic complications, especially stroke. Atrial fibrillation is a stronger risk factor than hypertension, coronary disease, or heart failure and is associated with an approximately five-fold increased risk. Mitigating stroke risk can be challenging and requires accurate assessment of stroke risk factors and careful selection of appropriate therapy. Anticoagulation, including the more recently introduced direct oral anticoagulants, is the standard of care for most patients. In addition, emerging non-pharmacologic mechanical interventions are playing an expanding role in reducing stroke risk in select patients. In this review we highlight the current approach to stroke risk stratification in atrial fibrillation and discuss in detail the mechanism, risks, and benefits of current and evolving therapies. Copyright © 2018 Elsevier Inc. All rights reserved.

[Team approaches to critical bleeding (massive bleeding and transfusion) - chairmen's introductory remarks. Questionnaire survey on current status of hospital clinical laboratories evaluating critical hemorrhage].

PubMed

Kino, Shuichi; Suwabe, Akira

2014-12-01

In 2007, "the Guidelines for Actions against Intraoperative Critical Hemorrhage" were established by the Japanese Society of Anaesthesiologists and the Japanese Society of Blood transfusion and Cell Therapy. The documentation of in-hospital procedures for critical hemorrhage, especially about how to select RBC units, has widely standardized hospital practice. Patients with intraoperative critical hemorrhage sometimes suffer from massive blood loss. In this situation, some patients develop coagulopathy. To treat them, we need to evaluate their coagulation status based on laboratory test results. So, we performed a nationwide questionnaire survey on the current status of hospital clinical laboratories evaluating critical hemorrhage. From the results of this survey, it was recommended that central hospital laboratories should try to reduce the turn-around time required to test for coagulation parameters as much as possible for appropriate substitution therapy. (Review).

Therapy of Chagas Disease: Implications for Levels of Prevention

PubMed Central

Sosa-Estani, Sergio; Colantonio, Lisandro; Segura, Elsa Leonor

2012-01-01

This paper reviews the evidence supporting the use of etiological treatment for Chagas disease that has changed the standard of care for patients with Trypanosoma cruzi infection in the last decades. Implications of this evidence on different levels of prevention as well as gaps in current knowledge are also discussed. In this regard, etiological treatment has shown to be beneficial as an intervention for secondary prevention to successfully cure the infection or to delay, reduce, or prevent the progression to disease, and as primary disease prevention by breaking the chain of transmission. Timely diagnosis during initial stages would allow for the prescription of appropriate therapies mainly in the primary health care system thus improving chances for a better quality of life. Based on current evidence, etiological treatment has to be considered as an essential public health strategy useful to reduce disease burden and to eliminate Chagas disease altogether. PMID:22523499

Urolift - minimally invasive surgical BPH management.

PubMed

Pushkaran, Anish; Stainer, Victoria; Muir, Gordon; Shergill, Iqbal S

2017-03-01

An ideal treatment option for symptomatic Benign Prostatic Hyperplasia (BPH) should relieve lower urinary tract symptoms (LUTS) and restore Quality of Life (QoL). Currently available medical therapies and surgical options for symptomatic BPH have side effects that adversely affects quality of life. Prostatic urethral lift (PUL) is a novel endourology procedure that promises to relieve LUTS without the aforementioned side effects. Areas covered: We diligently reviewed all the published literature on PUL, till July 2016 using standard search criteria. Expert commentary: There is good quality evidence to establish the efficiency of PUL in treating symptomatic BPH without adversely affecting the QoL. Based on the current literature, PUL can be considered as an option for those symptomatic BPH patients with small or medium size prostates (< 80 ml) without median lobe enlargement, who failed on medical therapy or are intolerant to it and wish to preserve their sexual function.

[Self-relaxation techniques for glaucoma patients. Significance of autogenic training, hypnosis and music therapy].

PubMed

Bertelmann, T; Strempel, I

2016-02-01

Glaucoma is currently the second most common cause of severe visual impairment and blindness worldwide. Standard pharmaceutical and surgical interventions often fail to prevent progression of glaucomatous optic neuropathy. To evaluate whether adjuvantly applied self-relaxation techniques can significantly impact intraocular pressure, ocular perfusion and the overall mental state of affected patients. A search of the literature was carried out and a comprehensive overview of currently available data is presented. Autogenic training, hypnosis and music therapy can significantly impact intraocular pressure, ocular perfusion and overall mental state of patients suffering from glaucoma. As all of these adjuvant therapeutic options are cost-effective, available almost everywhere and at anytime as well as without any known side effects, they can be useful additional techniques in the overall concept for treating glaucoma patients. Regular ocular examinations by an ophthalmologist are, however, mandatory.

Management of tinnitus in English NHS audiology departments: an evaluation of current practice

PubMed Central

Hoare, Derek J; Gander, Phillip E; Collins, Luke; Smith, Sandra; Hall, Deborah A

2012-01-01

Rationale, aim and objective In 2009, the UK Department of Health formalized recommended National Health Service practices for the management of tinnitus from primary care onwards. It is timely therefore to evaluate the perceived practicality, utility and impact of those guidelines in the context of current practice. Methods We surveyed current practice by posting a 36-item questionnaire to all audiology and hearing therapy staff that we were able to identify as being involved in tinnitus patient care in England. Results In total, 138 out of 351 clinicians responded (39% response rate). The findings indicate a consensus opinion that management should be tailored to individual symptom profiles but that there is little standardization of assessment procedures or tools in use. Conclusions While the lack of standardized practice might provide flexibility to meet local demand, it has drawbacks. It makes it difficult to ascertain key standards of best practice, it complicates the process of clinical audit, it implies unequal patient access to care, and it limits the implementation of translational research outcomes. We recommend that core elements of practice should be standardized, including use of a validated tinnitus questionnaires and an agreed pathway for decision making to better understand the rationale for management strategies offered. PMID:21087449

The performance implications of pharmacy information system at the university teaching hospitals of Shiraz, Iran: Cluster approach

PubMed Central

Bayati, Saeede; Bastani, Peivand; Sagheb, Zahra Mahmoodzade; Jamalabadi, Sara; Samadbeik, Mahnaz

2017-01-01

Pharmacy information system (PIS) is becoming vital in assisting pharmacists to do their responsibilities. The aim of this study was to identify the current PIS implications in teaching hospitals affiliated with Shiraz University of Medical Science. This cross-sectional study was conducted in teaching hospitals affiliated with Shiraz University of Medical Science over the year 2016. Data were collected by observing the PIS as well as interviewing its users based on the researcher-made checklist. The checklist was prepared based on reviewing the Persian and English literature and its content validity was approved by the experts. To determine the reliability of the checklist, inter-rater reliability was used. Data were analyzed using SPSS16, and hospitals were clustered using SK-means method. In this study, the least conformity to the standards was shown in smart clinical features (4.54%), pharmaceutical companies' relationship (32.6%), and optimization of drug therapy (34.6%). In contrast, the highest conformity to the standards was shown in reporting capabilities (77.3%) and entry information and input (70.4%). Medication stock checking and optimization of drug therapy were effective features that have made a distinction between hospitals and lead to 95% variance between clusters. Based on the results, the current PIS design pays less attention to clinical features. Besides, clinical information for pharmacists and outside organization relationship were not provided by the current system. Thus, emphasis should be placed on the implementation of corrective actions to eliminate the current system's deficiencies. PMID:29184843

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.

Osimertinib in the treatment of non-small-cell lung cancer: design, development and place in therapy.

PubMed

Santarpia, Mariacarmela; Liguori, Alessia; Karachaliou, Niki; Gonzalez-Cao, Maria; Daffinà, Maria Grazia; D'Aveni, Alessandro; Marabello, Grazia; Altavilla, Giuseppe; Rosell, Rafael

2017-01-01

The discovery of epidermal growth factor receptor ( EGFR ) mutations and subsequent demonstration of the efficacy of genotype-directed therapies with EGFR tyrosine kinase inhibitors (TKIs) marked the advent of the era of precision medicine for non-small-cell lung cancer (NSCLC). First- and second-generation EGFR TKIs, including erlotinib, gefitinib and afatinib, have consistently shown superior efficacy and better toxicity compared with first-line platinum-based chemotherapy and currently represent the standard of care for EGFR -mutated advanced NSCLC patients. However, tumors invariably develop acquired resistance to EGFR TKIs, thereby limiting the long-term efficacy of these agents. The T790M mutation in exon 20 of the EGFR gene has been identified as the most common mechanism of acquired resistance. Osimertinib is a third-generation TKI designed to target both EGFR TKI-sensitizing mutations and T790M, while sparing wild-type EGFR . Based on its pronounced clinical activity and good safety profile demonstrated in early Phase I and II trials, osimertinib received first approval in 2015 by the US FDA and in early 2016 by European Medicines Agency for the treatment of EGFR T790M mutation-positive NSCLC patients in progression after EGFR TKI therapy. Recent results from the Phase III AURA3 trial demonstrated the superiority of osimertinib over standard platinum-based doublet chemotherapy for treatment of patients with advanced EGFR T790M mutation-positive NSCLC with disease progression following first-line EGFR TKI therapy, thus definitively establishing this third-generation TKI as the standard of care in this setting. Herein, we review preclinical findings and clinical data from Phase I-III trials of osimertinib, including its efficacy in patients with central nervous system metastases. We further discuss currently available methods used to analyze T790M mutation status and the main mechanisms of resistance to osimertinib. Finally, we provide an outlook on ongoing trials with osimertinib and novel therapeutic combinations that might continue to improve the clinical outcome of EGFR -mutated NSCLC patients.

A systematic review of treatment response rates in Pakistani hepatitis C virus patients; current prospects and future challenges

PubMed Central

Ali, Muhammad; Afzal, Samia; Zia, Asad; Hassan, Ahmed; Khalil, Ali Talha; Ovais, Muhammad; Shinwari, Zabta Khan; Idrees, Muhammad

2016-01-01

Abstract Background: The estimated hepatitis C virus (HCV) carriers are approximately 10 million in Pakistan which usually progresses to chronic hepatitis, with rare cases of spontaneous viral eradication. The present article reviews the treatment status of HCV infection in Pakistani population and various factors associated with the treatment response rates. Methods: Literature on anti-HCV therapy was searched in PubMed, Google Scholar and PakMediNet. Thirty three different studies representing different geographic regions of Pakistan published from 2002 to 2016 were included in the present review. Weighted mean, standard error estimates (SE) and standard deviation (SD) were determined for each population group. Results: Mean value for sustained virological response (SVR) for standard IFN plus ribavirin (RBV) combination therapy was 68.38% ± 14.13% (range 33.8%–87.10%; SE 3.08) and pegylated-IFN plus RBV combination therapy 64.38% ± 8.68% (range 55.0%–76.00%; SE 3.88). The lowest value for SVR has been reported to be 24.3% (for genotype 1; administering INF-α 2b 3MU 3 times/week and RBV 1000–1200 mg/day for 48 weeks) while highest of 87.5% (genotype 3a; INF-α 2a 3MU 3 times/week and RBV 1000–1200 mg/day for 24 weeks). The mean value for rapid virological response (RVR) was found to be 48.18% ± 29.20% (SE 9.73). As PEG-interferon and direct acting antivirals (DAAs) are relatively expensive, interferon-alfa (IFN-α) and RBV combination therapy have been used widely to treat HCV infected patients in Pakistan for the last one and half decade. On average, 2.45% of the patients discontinued treatment due to severe side effects. Conclusion: We encourage further studies on understanding host and viral factors associated with specific focus on harder to treat viral variants (relapsers and nonresponders). These variants are currently rising in the country. PMID:27977575

Osimertinib in the treatment of non-small-cell lung cancer: design, development and place in therapy

PubMed Central

Santarpia, Mariacarmela; Liguori, Alessia; Karachaliou, Niki; Gonzalez-Cao, Maria; Daffinà, Maria Grazia; D’Aveni, Alessandro; Marabello, Grazia; Altavilla, Giuseppe; Rosell, Rafael

2017-01-01

The discovery of epidermal growth factor receptor (EGFR) mutations and subsequent demonstration of the efficacy of genotype-directed therapies with EGFR tyrosine kinase inhibitors (TKIs) marked the advent of the era of precision medicine for non-small-cell lung cancer (NSCLC). First- and second-generation EGFR TKIs, including erlotinib, gefitinib and afatinib, have consistently shown superior efficacy and better toxicity compared with first-line platinum-based chemotherapy and currently represent the standard of care for EGFR-mutated advanced NSCLC patients. However, tumors invariably develop acquired resistance to EGFR TKIs, thereby limiting the long-term efficacy of these agents. The T790M mutation in exon 20 of the EGFR gene has been identified as the most common mechanism of acquired resistance. Osimertinib is a third-generation TKI designed to target both EGFR TKI-sensitizing mutations and T790M, while sparing wild-type EGFR. Based on its pronounced clinical activity and good safety profile demonstrated in early Phase I and II trials, osimertinib received first approval in 2015 by the US FDA and in early 2016 by European Medicines Agency for the treatment of EGFR T790M mutation-positive NSCLC patients in progression after EGFR TKI therapy. Recent results from the Phase III AURA3 trial demonstrated the superiority of osimertinib over standard platinum-based doublet chemotherapy for treatment of patients with advanced EGFR T790M mutation-positive NSCLC with disease progression following first-line EGFR TKI therapy, thus definitively establishing this third-generation TKI as the standard of care in this setting. Herein, we review preclinical findings and clinical data from Phase I–III trials of osimertinib, including its efficacy in patients with central nervous system metastases. We further discuss currently available methods used to analyze T790M mutation status and the main mechanisms of resistance to osimertinib. Finally, we provide an outlook on ongoing trials with osimertinib and novel therapeutic combinations that might continue to improve the clinical outcome of EGFR-mutated NSCLC patients. PMID:28860885

Novel and Effective Therapeutic Regimens for Helicobacter pylori in an Era of Increasing Antibiotic Resistance

PubMed Central

Hu, Yi; Zhu, Yin; Lu, Nong-Hua

2017-01-01

Helicobacter pylori (H. pylori) is a common gastrointestinal bacterial strain closely associated with the incidence of chronic gastritis, peptic ulcers, gastric mucosa-associated lymphoid tissue lymphoma, and gastric cancer. A current research and clinical challenge is the increased rate of antibiotic resistance in H. pylori, which has led to a decreased H. pylori eradication rate. In this article, we review recent H. pylori infection and reinfection rates and H. pylori resistance to antibiotics, and we discuss the pertinent treatments. A PubMed literature search was performed using the following keywords: Helicobacter pylori, infection, reinfection, antibiotic resistance, bismuth, proton pump inhibitors, vonoprazan, susceptibility, quintuple therapy, dual therapy, and probiotic. The prevalence of H. pylori has remained high in some areas despite the decreasing trend of H. pylori prevalence observed over time. Additionally, the H. pylori reinfection rate has varied in different countries due to socioeconomic and hygienic conditions. Helicobacter pylori monoresistance to clarithromycin, metronidazole or levofloxacin was common in most countries. However, the prevalence of amoxicillin and tetracycline resistance has remained low. Because H. pylori infection and reinfection present serious challenges and because H. pylori resistance to clarithromycin, metronidazole or levofloxacin remains high in most countries, the selection of an efficient regimen to eradicate H. pylori is critical. Currently, bismuth-containing quadruple therapies still achieve high eradication rates. Moreover, susceptibility-based therapies are alternatives because they may avoid the use of unnecessary antibiotics. Novel regimens, e.g., vonoprazan-containing triple therapies, quintuple therapies, high-dose dual therapies, and standard triple therapies with probiotics, require further studies concerning their efficiency and safety for treating H. pylori. PMID:28529929

Multicenter study of combination DEP regimen as a salvage therapy for adult refractory hemophagocytic lymphohistiocytosis.

PubMed

Wang, Yini; Huang, Wenqiu; Hu, Liangding; Cen, Xinan; Li, Lihong; Wang, Jijun; Shen, Jianliang; Wei, Na; Wang, Zhao

2015-11-05

Hemophagocytic lymphohistiocytosis (HLH) is a refractory immune disorder with a significant risk of death. Although standard therapy has dramatically improved survival in HLH patients, approximately 30%, especially adults, show no response to current treatment strategies. This prospective study aimed to investigate the efficacy of liposomal doxorubicin treatment combined with etoposide and methylprednisolone (doxorubicin-etoposide-methylprednisolone; DEP) as a salvage therapy for adult refractory HLH. Adult patients who did not achieve at least partial response 2 weeks after initial standard HLH therapy were enrolled in this study between June 2013 and June 2014. Response to salvage therapy was assessed at 2 and 4 weeks after initiation of DEP therapy and patients were followed until death or until November 2014. Sixty-three refractory HLH patients were enrolled, including 29 cases of lymphoma-associated HLH, 22 cases of Epstein-Barr virus-associated HLH, and 4 cases of familial HLH. There were 8 cases with unknown underlying diseases. Seventeen cases (27.0%) achieved complete response and 31 cases (49.2%) achieved partial response. The overall response was 76.2% (48/63). Patients who showed no response to DEP died within 4 weeks after salvage therapy. Twenty-nine of the 48 patients who achieved partial or complete response survived to subsequent chemotherapy, allogenic hematopoietic stem cell transplantation, or splenectomy. Our study suggests that DEP regimen is an effective salvage regimen for adult refractory HLH, which can prolong patient survival as we continue to understand the responsible mechanisms and bridge the gap between HLH and its underlying diseases. This study was registered in the Chinese Clinical Trials Registry Platform (http://www.chictr.org.cn/) as ChiCTR-IPC-14005514. © 2015 by The American Society of Hematology.

Meta-Analysis of Massage Therapy on Cancer Pain.

PubMed

Lee, Sook-Hyun; Kim, Jong-Yeop; Yeo, Sujung; Kim, Sung-Hoon; Lim, Sabina

2015-07-01

Cancer pain is the most common complaint among patients with cancer. Conventional treatment does not always relieve cancer pain satisfactorily. Therefore, many patients with cancer have turned to complementary therapies to help them with their physical, emotional, and spiritual well-being. Massage therapy is increasingly used for symptom relief in patients with cancer. The current study aimed to investigate by meta-analysis the effects of massage therapy for cancer patients experiencing pain. Nine electronic databases were systematically searched for studies published through August 2013 in English, Chinese, and Korean. Methodological quality was assessed using the Physiotherapy Evidence Database (PEDro) and Cochrane risk-of-bias scales. Twelve studies, including 559 participants, were used in the meta-analysis. In 9 high-quality studies based on the PEDro scale (standardized mean difference, -1.24; 95% confidence interval, -1.72 to -0.75), we observed reduction in cancer pain after massage. Massage therapy significantly reduced cancer pain compared with no massage treatment or conventional care (standardized mean difference, -1.25; 95% confidence interval, -1.63 to -0.87). Our results indicate that massage is effective for the relief of cancer pain, especially for surgery-related pain. Among the various types of massage, foot reflexology appeared to be more effective than body or aroma massage. Our meta-analysis indicated a beneficial effect of massage for relief of cancer pain. Further well-designed, large studies with longer follow-up periods are needed to be able to draw firmer conclusions regarding the effectiveness. © The Author(s) 2015.

Health economics of treating haemophilia A with inhibitors.

PubMed

Knight, C

2005-11-01

Haemophilia is a rare, inherited blood disorder in which blood clotting is impaired such that patients suffer from excessive internal and external bleeding. At present there is no cure for haemophilia A and patients require expensive, life-long treatment involving clotting factor replacement therapy. Treatment costs are perceived to be higher for patients who have developed inhibitory antibodies to factor VIII, the standard therapy for haemophilia A. However, initial cost analyses suggest that clotting factor therapy with alternative haemostatic agents, such as recombinant activated factor VII or activated prothrombin complex concentrate, is no more expensive for the majority of haemophilia A patients with inhibitors than for those without inhibitors. With the availability of effective alternative haemostatic agents, orthopaedic surgery for haemophilia A patients with inhibitors is now a clinical option, and initial cost analyses suggest this may be a cost-effective treatment strategy for patients with inhibitors whose quality of life (QoL) is severely impaired by joint arthropathy. In an era of finite healthcare resourcing it is important to determine whether new treatments justify higher unit costs compared with standard therapies and whether such higher costs are justified from an individual perspective in terms of improved QoL, and from a societal perspective in terms of improved productivity and reduced overall healthcare costs. This paper examines current data on the health economics of treating haemophilia A patients with inhibitors, focusing on the overall costs of clotting factor replacement therapy and the cost consequences of joint replacement.

Radiation therapy and esophageal cancer.

PubMed

Shridhar, Ravi; Almhanna, Khaldoun; Meredith, Kenneth L; Biagioli, Matthew C; Chuong, Michael D; Cruz, Alex; Hoffe, Sarah E

2013-04-01

Squamous cell carcinoma and adenocarcinoma account for more than 90% of all esophageal cancer cases. Although the incidence of squamous cell carcinoma has declined, the incidence of adenocarcinoma has risen due to increases in obesity and gastroesophageal reflux disease. The authors examine the role of radiation therapy alone (external beam and brachytherapy) for the management of esophageal cancer or combined with other modalities. The impact on staging and appropriate stratification of patients referred for curative vs palliative intent with modalities is reviewed. The authors also explore the role of emerging radiation technologies. Current data show that neoadjuvant chemoradiotherapy followed by surgical resection is the accepted standard of care, with 3-year overall survival rates ranging from 30% to 60%. The benefit of adjuvant radiation therapy is limited to patients with node-positive cancer. The survival benefit of surgical resection after chemoradiotherapy remains controversial. External beam radiation therapy alone results in few long-term survivors and is considered palliative at best. Radiation dose-escalation has failed to improve local control or survival. Brachytherapy can provide better long-term palliation of dysphagia than metal stent placement. Although three-dimensional conformal treatment planning is the accepted standard, the roles of IMRT and proton therapy are evolving and potentially reduce adverse events due to better sparing of normal tissue. Future directions will evaluate the benefit of induction chemotherapy followed by chemoradiotherapy, the role of surgery in locally advanced disease, and the identification of responders prior to treatment based on microarray analysis.

Using non-invasive brain stimulation to augment motor training-induced plasticity

PubMed Central

Bolognini, Nadia; Pascual-Leone, Alvaro; Fregni, Felipe

2009-01-01

Therapies for motor recovery after stroke or traumatic brain injury are still not satisfactory. To date the best approach seems to be the intensive physical therapy. However the results are limited and functional gains are often minimal. The goal of motor training is to minimize functional disability and optimize functional motor recovery. This is thought to be achieved by modulation of plastic changes in the brain. Therefore, adjunct interventions that can augment the response of the motor system to the behavioural training might be useful to enhance the therapy-induced recovery in neurological populations. In this context, noninvasive brain stimulation appears to be an interesting option as an add-on intervention to standard physical therapies. Two non-invasive methods of inducing electrical currents into the brain have proved to be promising for inducing long-lasting plastic changes in motor systems: transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS). These techniques represent powerful methods for priming cortical excitability for a subsequent motor task, demand, or stimulation. Thus, their mutual use can optimize the plastic changes induced by motor practice, leading to more remarkable and outlasting clinical gains in rehabilitation. In this review we discuss how these techniques can enhance the effects of a behavioural intervention and the clinical evidence to date. PMID:19292910

Comparison of efficacy and safety of levofloxacin-containing versus standard sequential therapy in eradication of Helicobacter pylori infection in Korea.

PubMed

Lee, Hyuk; Hong, Sung Noh; Min, Byung-Hoon; Lee, Jun Haeng; Rhee, Poong-Lyul; Lee, Yong Chan; Kim, Jae J

2015-02-01

Declining of eradication rates for Helicobacter pylori in Korea may be partly from the increasing prevalence of antibiotic resistance, especially clarithromycin resistance. To compare the efficacy and the safety of using 10-day standard sequential therapy and levofloxacin-containing sequential therapy as a first-line treatment for Helicobacter pylori eradication in Korea. A total of 200 patients with proven Helicobacter pylori infection randomly received 10-day standard sequential therapy (n = 100) or levofloxacin-containing sequential therapy (n = 100). The standard sequential therapy group received rabeprazole and amoxicillin for 5 days, followed by rabeprazole, clarithromycin, and metronidazole for 5 more days. The levofloxacin-containing sequential therapy group was treated with rabeprazole and amoxicillin for 5 days, followed by rabeprazole, levofloxacin, and metronidazole for 5 more days. Intention-to-treat eradication rates were 79.0% and 78.0% for groups of standard sequential and levofloxacin-containing sequential therapy, respectively (P = 0.863). Per-protocol eradication rates were 84.9% and 81.3%, respectively, for these two therapies (P = 0.498). There were no significant differences between the groups in regard to the eradication rates and adverse events. The 10-day levofloxacin-containing sequential regimen and the standard sequential regimen showed the similar eradication rates of Helicobacter pylori in Korea. Copyright © 2014 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Thrombolytic therapy for mitral valve thrombosis.

PubMed

Lin, T K; Tsai, L M; Chen, J H; Yang, Y J

1997-05-01

A 44-year-old man with a St. Jude mitral valve was admitted because of progressive pulmonary edema. He was diagnosed with prosthetic heart valve thrombosis (PHVT) based on the findings of "muffled" prosthetic valve clicks. Doppler echocardiographic evidence of severe mitral stenosis and transesophageal echocardiographic evidence of limited mitral valve motility. Because the patient hesitated to undergo our recommended surgical treatment, he was immediately treated with intravenous recombinant tissue plasminogen activator (100 mg over 3 h) followed by heparinization. Two hours after the thrombolytic therapy, the prosthetic valve clicks became clearly audible and his congestive symptoms were dramatically improved. Follow-up echocardiography no longer-showed significant mitral valve obstruction. A transient cerebral ischemic attack occurred at the end of thrombolytic therapy but there were no neurologic sequalae. The patient, on warfarin therapy, was well at follow-up 8 months after discharge. Surgical intervention has long been the standard therapy for patients with PHVT. Our case experience suggests that thrombolytic therapy may be considered as an effective alternative to surgical intervention for selected patients with PHVT. In this report, we also review the current literature regarding the indications, effectiveness and safety of thrombolytic therapy in PHVT.

Levofloxacin-Based First-Line Therapy versus Standard First-Line Therapy for Helicobacter pylori Eradication: Meta-Analysis of Randomized Controlled Trials

PubMed Central

Peedikayil, Musthafa Chalikandy; AlSohaibani, Fahad Ibrahim; Alkhenizan, Abdullah Hamad

2014-01-01

Background First-line levofloxacin-based treatments eradicate Helicobacter pylori with varying success. We examined the efficacy and safety of first-line levofloxacin-based treatment in comparison to standard first-line therapy for H pylori eradication. Materials and Methods We searched literature databases from Medline, EMBASE, and the Cochrane Register of Randomized Controlled Trials through March 2013 for randomized controlled trials comparing first-line levofloxacin and standard therapy. We included randomized controlled trials conducted only on naïve H pylori infected patients in adults. A systematic review was conducted. Meta-analysis was performed with Review Manager 5.2. Treatment effect was determined by relative risk with a random or fixed model by the Mantel-Haenszel method. Results Seven trials were identified with 888 patients receiving 7 days of first-line levofloxacin and 894 treated with standard therapy (Amoxicillin, Clarithromycin and proton pump inhibitor) for 7 days. The overall crude eradication rate in the Levofloxacin group was 79.05% versus 81.4% in the standard group (risk ratio 0.97; 95% CI; 0.93, 1.02). The overall dropout was 46 (5.2%) in the levofloxacin group and 52 (5.8%) for standard therapy. The dizziness was more common among group who took Levofloxacin based treatment and taste disturbance was more common among group who took standard therapy. Meta-analysis of overall adverse events were similar between the two groups with a relative risk of 1.06 (95% CI 0.72, 1.57). Conclusion Helicobacter pylori eradication with 7 days of Levofloxacin-based first line therapy was safe and equal compared to 7 days of standard first-line therapy. PMID:24465624

Clinical Case Reporting in the Peer-Reviewed Physical Therapy Literature: Time to Move Toward Functioning.

PubMed

Davenport, Todd E

2015-12-01

Physical therapists increasingly are contributing clinical case reports to the health literature, which form the basis for higher quality evidence that has been incorporated into clinical practice guidelines. Yet, few resources exist to assist physical therapists with the basic mechanics and quality standards of producing a clinical case report. This situation is further complicated by the absence of uniform standards for quality in case reporting. The importance of including a concise yet comprehensive description of patient functioning in all physical therapy case reports suggest the potential appropriateness of basing quality guidelines on the World Health Organization's International Classification of Functioning Disability and Health (ICF) model. The purpose of this paper is to assist physical therapists in creating high-quality clinical case reports for the peer-reviewed literature using the ICF model as a guiding framework. Along these lines, current recommendations related to the basic mechanics of writing a successful clinical case report are reviewed, as well and a proposal for uniform clinical case reporting requirements is introduced with the aim to improve the quality and feasibility of clinical case reporting in physical therapy that are informed by the ICF model. Copyright © 2013 John Wiley & Sons, Ltd.

Non-thermal irreversible electroporation (N-TIRE) and adjuvant fractionated radiotherapeutic multimodal therapy for intracranial malignant glioma in a canine patient.

PubMed

Garcia, P A; Pancotto, T; Rossmeisl, J H; Henao-Guerrero, N; Gustafson, N R; Daniel, G B; Robertson, J L; Ellis, T L; Davalos, R V

2011-02-01

Non-thermal irreversible electroporation (N-TIRE) has shown promise as an ablative therapy for a variety of soft-tissue neoplasms. Here we describe the therapeutic planning aspects and first clinical application of N-TIRE for the treatment of an inoperable, spontaneous malignant intracranial glioma in a canine patient. The N-TIRE ablation was performed safely, effectively reduced the tumor volume and associated intracranial hypertension, and provided sufficient improvement in neurological function of the patient to safely undergo adjunctive fractionated radiotherapy (RT) according to current standards of care. Complete remission was achieved based on serial magnetic resonance imaging examinations of the brain, although progressive radiation encephalopathy resulted in the death of the dog 149 days after N-TIRE therapy. The length of survival of this patient was comparable to dogs with intracranial tumors treated via standard excisional surgery and adjunctive fractionated external beam RT. Our results illustrate the potential benefits of N-TIRE for in vivo ablation of undesirable brain tissue, especially when traditional methods of cytoreductive surgery are not possible or ideal, and highlight the potential radiosensitizing effects of N-TIRE on the brain.

Developing laser-based therapy monitoring of early caries in pediatric dental settings

NASA Astrophysics Data System (ADS)

Zhou, Yaxuan; Jiang, Yang; Kim, Amy S.; Xu, Zheng; Berg, Joel H.; Seibel, Eric J.

2017-02-01

Optical imaging modalities and therapy monitoring protocols are required for the emergence of non-surgical interventions for treating infections in teeth to remineralize the enamel. Current standard of visual inspection, tactile probing and radiograph for caries detection is not highly sensitive, quantitative, and safe. Furthermore, the latter two are not viable options for interproximal caries. We present preliminary results of multimodal laser-based imaging and uorescence spectroscopy in a blinded clinical study comparing two topical therapies of early interproximal caries in children. With a spacer placed interproximally both at baseline and followup examinations, the 405-nm excited red porphyrin uorescence imaging with green auto uorescence is measured and compared to a 12-month follow-up. 405-nm laser-induced uorescence spectroscopy is also measured from the center of selected multimodal video imaging frames. These results of three subjects are analyzed both qualitatively by comparing spectra and quantitatively based on uorescence region segmentation, and then are compared to the standard of care(visual examination and radiograph interpretation). Furthermore, this study points out challenges associated with optically monitoring non-surgical dental interventions over long periods of time in clinical practice and also indicates future direction for improvement on the protocol.

Non-Thermal Irreversible Electroporation (N-TIRE) and Adjuvant Fractionated Radiotherapeutic Multimodal Therapy for Intracranial Malignant Glioma in a Canine Patient

PubMed Central

Garcia, P. A.; Pancotto, T.; Rossmeisl, J. H.; Henao-Guerrero, N.; Gustafson, N. R.; Daniel, G. B.; Robertson, J. L.; Ellis, T. L.; Davalos, R. V.

2011-01-01

Non-thermal irreversible electroporation (N-TIRE) has shown promise as an ablative therapy for a variety of soft-tissue neoplasms. Here we describe the therapeutic planning aspects and first clinical application of N-TIRE for the treatment of an inoperable, spontaneous malignant intracranial glioma in a canine patient. The N-TIRE ablation was performed safely, effectively reduced the tumor volume and associated intracranial hypertension, and provided sufficient improvement in neurological function of the patient to safely undergo adjunctive fractionated radiotherapy (RT) according to current standards of care. Complete remission was achieved based on serial magnetic resonance imaging examinations of the brain, although progressive radiation encephalopathy resulted in the death of the dog 149 days after N-TIRE therapy. The length of survival of this patient was comparable to dogs with intracranial tumors treated via standard excisional surgery and adjunctive fractionated external beam RT. Our results illustrate the potential benefits of N-TIRE for in vivo ablation of undesirable brain tissue, especially when traditional methods of cytoreductive surgery are not possible or ideal, and highlight the potential radiosensitizing effects of N-TIRE on the brain. PMID:21214290

Preclinical testing of an Atr inhibitor demonstrates improved response to standard therapies for esophageal cancer.

PubMed

Leszczynska, Katarzyna B; Dobrynin, Greg; Leslie, Rhea E; Ient, Jonathan; Boumelha, Adam J; Senra, Joana M; Hawkins, Maria A; Maughan, Tim; Mukherjee, Somnath; Hammond, Ester M

2016-11-01

Esophageal cancer has a persistently low 5-year survival rate and has recently been classified as a cancer of unmet need by Cancer Research UK. Consequently, new approaches to therapy are urgently required. Here, we tested the hypothesis that an ATR inhibitor, VX-970, used in combination with standard therapies for esophageal cancer could improve treatment outcome. Using esophageal cancer cell lines we evaluated the efficacy of combining VX-970 with cisplatin and carboplatin in vitro and with radiation in vitro and in vivo. Radiation experiments were also carried out in hypoxic conditions to mimic the tumor microenvironment. Combining VX-970 with cisplatin, carboplatin and radiation increased tumor cell kill in vitro. A significant tumor growth delay was observed when VX-970 was combined with radiotherapy in vivo. VX-970 is an effective chemo/radiosensitizer which could be readily integrated in the current treatment paradigm to improve the treatment response in esophageal cancer and we plan to test it prospectively in the forthcoming phase I dose escalation safety study combining the ATR inhibitor VX-970 with chemoradiotherapy in esophageal cancer (EudraCT number: 2015-003965-27). Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Yoga Therapy and Polyvagal Theory: The Convergence of Traditional Wisdom and Contemporary Neuroscience for Self-Regulation and Resilience

PubMed Central

Sullivan, Marlysa B.; Erb, Matt; Schmalzl, Laura; Moonaz, Steffany; Noggle Taylor, Jessica; Porges, Stephen W.

2018-01-01

Yoga therapy is a newly emerging, self-regulating complementary and integrative healthcare (CIH) practice. It is growing in its professionalization, recognition and utilization with a demonstrated commitment to setting practice standards, educational and accreditation standards, and promoting research to support its efficacy for various populations and conditions. However, heterogeneity of practice, poor reporting standards, and lack of a broadly accepted understanding of the neurophysiological mechanisms involved in yoga therapy limits the structuring of testable hypotheses and clinical applications. Current proposed frameworks of yoga-based practices focus on the integration of bottom-up neurophysiological and top-down neurocognitive mechanisms. In addition, it has been proposed that phenomenology and first person ethical inquiry can provide a lens through which yoga therapy is viewed as a process that contributes towards eudaimonic well-being in the experience of pain, illness or disability. In this article we build on these frameworks, and propose a model of yoga therapy that converges with Polyvagal Theory (PVT). PVT links the evolution of the autonomic nervous system to the emergence of prosocial behaviors and posits that the neural platforms supporting social behavior are involved in maintaining health, growth and restoration. This explanatory model which connects neurophysiological patterns of autonomic regulation and expression of emotional and social behavior, is increasingly utilized as a framework for understanding human behavior, stress and illness. Specifically, we describe how PVT can be conceptualized as a neurophysiological counterpart to the yogic concept of the gunas, or qualities of nature. Similar to the neural platforms described in PVT, the gunas provide the foundation from which behavioral, emotional and physical attributes emerge. We describe how these two different yet analogous frameworks—one based in neurophysiology and the other in an ancient wisdom tradition—highlight yoga therapy’s promotion of physical, mental and social wellbeing for self-regulation and resilience. This parallel between the neural platforms of PVT and the gunas of yoga is instrumental in creating a translational framework for yoga therapy to align with its philosophical foundations. Consequently, yoga therapy can operate as a distinct practice rather than fitting into an outside model for its utilization in research and clinical contexts. PMID:29535617

Ruxolitinib versus standard therapy for the treatment of polycythemia vera.

PubMed

Vannucchi, Alessandro M; Kiladjian, Jean Jacques; Griesshammer, Martin; Masszi, Tamas; Durrant, Simon; Passamonti, Francesco; Harrison, Claire N; Pane, Fabrizio; Zachee, Pierre; Mesa, Ruben; He, Shui; Jones, Mark M; Garrett, William; Li, Jingjin; Pirron, Ulrich; Habr, Dany; Verstovsek, Srdan

2015-01-29

Ruxolitinib, a Janus kinase (JAK) 1 and 2 inhibitor, was shown to have a clinical benefit in patients with polycythemia vera in a phase 2 study. We conducted a phase 3 open-label study to evaluate the efficacy and safety of ruxolitinib versus standard therapy in patients with polycythemia vera who had an inadequate response to or had unacceptable side effects from hydroxyurea. We randomly assigned phlebotomy-dependent patients with splenomegaly, in a 1:1 ratio, to receive ruxolitinib (110 patients) or standard therapy (112 patients). The primary end point was both hematocrit control through week 32 and at least a 35% reduction in spleen volume at week 32, as assessed by means of imaging. The primary end point was achieved in 21% of the patients in the ruxolitinib group versus 1% of those in the standard-therapy group (P<0.001). Hematocrit control was achieved in 60% of patients receiving ruxolitinib and 20% of those receiving standard therapy; 38% and 1% of patients in the two groups, respectively, had at least a 35% reduction in spleen volume. A complete hematologic remission was achieved in 24% of patients in the ruxolitinib group and 9% of those in the standard-therapy group (P=0.003); 49% versus 5% had at least a 50% reduction in the total symptom score at week 32. In the ruxolitinib group, grade 3 or 4 anemia occurred in 2% of patients, and grade 3 or 4 thrombocytopenia occurred in 5%; the corresponding percentages in the standard-therapy group were 0% and 4%. Herpes zoster infection was reported in 6% of patients in the ruxolitinib group and 0% of those in the standard-therapy group (grade 1 or 2 in all cases). Thromboembolic events occurred in one patient receiving ruxolitinib and in six patients receiving standard therapy. In patients who had an inadequate response to or had unacceptable side effects from hydroxyurea, ruxolitinib was superior to standard therapy in controlling the hematocrit, reducing the spleen volume, and improving symptoms associated with polycythemia vera. (Funded by Incyte and others; RESPONSE ClinicalTrials.gov number, NCT01243944.).

[The current state and prospect of Chinese medicine gastroenterology].

PubMed

Zhang, Sheng-Sheng; Zhou, Tao

2012-03-01

The progress and existent problems of Chinese medicine (CM) gastroenterology since the National Eleventh Five-Year Plan were discussed in this article in terms of theory innovation, formulation of clinical pathway and diagnosis-treatment consensus, efficacy assessment, formulation of efficacy assessment scale, advantage diseases, and exploration of the syndrome standardization, progress in science research, academic exchange, and the construction of study platform, and so on. Meanwhile, the development of CM gastroenterology was prospected in the following five aspects: to enhance the theory inheritance and innovation, the construction of discipline standardization; to establish scientific clinical efficacy assessment methods and the standard system; to expend treatment technologies and feature therapies; and to clarify the modern scientific connotation of CM theory and treatment.

Costs of bronchoalveolar lavage-directed therapy in the first 5 years of life for children with cystic fibrosis.

PubMed

Moodie, Marj; Lal, Anita; Vidmar, Suzanna; Armstrong, David S; Byrnes, Catherine A; Carlin, John B; Cheney, Joyce; Cooper, Peter J; Grimwood, Keith; Robertson, Colin F; Tiddens, Harm A; Wainwright, Claire E

2014-09-01

To determine whether bronchoalveolar lavage (BAL)-directed therapy for infants and young children with cystic fibrosis (CF), rather than standard therapy, was justified on the grounds of a decrease in average costs and whether the use of BAL reduced treatment costs associated with hospital admissions. Costs were assessed in a randomized controlled trial conducted in Australia and New Zealand on infants diagnosed with CF after newborn screening and assigned to receive either BAL-directed or standard therapy until they reached 5 years of age. A health care funder perspective was adopted. Resource use measurement was based on standardized data collection forms administered for patients across all sites. Unit costs were obtained primarily from government schedules. Mean costs per child during the study period were Australian dollars (AUD)92 860 in BAL-directed therapy group and AUD90 958 in standard therapy group (mean difference AUD1902, 95% CI AUD-27 782 to 31 586, P = .90). Mean hospital costs per child during the study period were AUD57 302 in the BAL-directed therapy group and AUD66 590 in the standard therapy group (mean difference AUD-9288; 95% CI AUD-35 252 to 16 676, P = .48). BAL-directed therapy did not result in either lower mean hospital admission costs or mean costs overall compared with managing patients with CF by a standard protocol based upon clinical features and oropharyngeal culture results alone. Following on our previous findings that BAL-directed treatment offers no clinical advantage over standard therapy at age 5 years, flexible bronchoscopy with BAL cannot be recommended for the routine management of preschool children with CF on the basis of overall cost savings. Copyright © 2014 Elsevier Inc. All rights reserved.

A comparison of international occupational therapy competencies: implications for Australian standards in the new millennium.

PubMed

Rodger, Sylvia; Clark, Michele; Banks, Rebecca; O'Brien, Mia; Martinez, Kay

2009-12-01

A timely evaluation of the Australian Competency Standards for Entry-Level Occupational Therapists (1994) was conducted. This thorough investigation comprised a literature review exploring the concept of competence and the applications of competency standards; systematic benchmarking of the Australian Occupational Therapy Competency Standards (OT AUSTRALIA, 1994) against other national and international competency standards and other affiliated documents, from occupational therapy and other cognate disciplines; and extensive nationwide consultation with the professional community. This paper explores and examines the similarities and disparities between occupational therapy competency standards documents available in English from Australia and other countries. An online search for national occupational therapy competency standards located 10 documents, including the Australian competencies. Four 'frameworks' were created to categorise the documents according to their conceptual underpinnings: Technical-Prescriptive, Enabling, Educational and Meta-Cognitive. Other characteristics that appeared to impact the design, content and implementation of competency standards, including definitions of key concepts, authorship, national and cultural priorities, scope of services, intended use and review mechanisms, were revealed. The proposed 'frameworks' and identification of influential characteristics provided a 'lens' through which to understand and evaluate competency standards. While consistent application of and attention to some of these characteristics appear to consolidate and affirm the authority of competency standards, it is suggested that the national context should be a critical determinant of the design and content of the final document. The Australian Occupational Therapy Competency Standards (OT AUSTRALIA, 1994) are critiqued accordingly, and preliminary recommendations for revision are proposed.

Decision-Making Strategy for Rectal Cancer Management Using Radiation Therapy for Elderly or Comorbid Patients.

PubMed

Wang, Shang-Jui; Hathout, Lara; Malhotra, Usha; Maloney-Patel, Nell; Kilic, Sarah; Poplin, Elizabeth; Jabbour, Salma K

2018-03-15

Rectal cancer predominantly affects patients older than 70 years, with peak incidence at age 80 to 85 years. However, the standard treatment paradigm for rectal cancer oftentimes cannot be feasibly applied to these patients owing to frailty or comorbid conditions. There are currently little information and no treatment guidelines to help direct therapy for patients who are elderly and/or have significant comorbidities, because most are not included or specifically studied in clinical trials. More recently various alternative treatment options have been brought to light that may potentially be utilized in this group of patients. This critical review examines the available literature on alternative therapies for rectal cancer and proposes a treatment algorithm to help guide clinicians in treatment decision making for elderly and comorbid patients. Copyright © 2017 Elsevier Inc. All rights reserved.

Genital Warts

PubMed Central

Yanofsky, Valerie R.; Patel, Rita V.

2012-01-01

External genital warts, also known as condylomata acuminata, are extremely common, with between 500,000 to one million new cases diagnosed each year in the United States alone. To date, more than 120 distinct subtypes of human papillomavirus have been identified. Human papillomavirus types 6 and 11 rarely give rise to cervical cancers, but are responsible for 90 percent of the cases of genital warts. The current treatment options are largely centered upon removal of the warts rather than elimination of the underlying viral infection. A wide range of therapies are presently in use, which are highly variable and can differ dramatically with respect to cost, side-effect profiles, dosing schedules, duration of treatment, and overall effectiveness. As of yet, no definitive therapy has emerged as the ideal standard of care in the treatment of genital warts, and therapy selection generally occurs in a patient-specific manner. PMID:22768354

Inappropriate Implantable Cardioverter-Defibrillator Shocks Attributed to Alternating-Current Leak in a Swimming Pool

PubMed Central

Makaryus, John N.; Angert-Gilman, Julia; Yacoub, Mena; Patel, Apoor

2014-01-01

Implantable cardioverter-defibrillators (ICDs) are the standard of care for preventing sudden cardiac death in patients who are predisposed to malignant ventricular arrhythmias. Causes of inappropriate ICD shock include equipment malfunction, improper arrhythmia evaluation, misinterpretation of myopotentials, and electromagnetic interference. As the number of implanted ICDs has increased, other contributors to inappropriate therapy have become known, such as minimal electrical current leaks that mimic ventricular fibrillation. We present the case of a 63-year-old man with a biventricular ICD who received 2 inappropriate shocks, probably attributable to alternating-current leaks in a swimming pool. In addition, we discuss ICD sensitivity and offer recommendations to avoid similar occurrences. PMID:24512403

Metformin Therapy for Fanconis Anemia

DTIC Science & Technology

2017-08-01

Specifically, the commonly used diabetes drug metformin will be tested by itself and in combination with the current standard of care, anabolic steroids...pertains to the treatment of the inherited bone marrow failure syndrome Fanconi’s Anemia. Specifically, the commonly used diabetes drug metformin will be... drug , small molecule, DNA damage, metformin 3. Accomplishments We started work on this project less than a year ago and already have made good progress

Current management of penetrating torso trauma: nontherapeutic is not good enough anymore

PubMed Central

Ball, Chad G.

2014-01-01

A highly organized approach to the evaluation and treatment of penetrating torso injuries based on regional anatomy provides rapid diagnostic and therapeutic consistency. It also minimizes delays in diagnosis, missed injuries and nontherapeutic laparotomies. This review discusses an optimal sequence of structured rapid assessments that allow the clinician to rapidly proceed to gold standard therapies with a minimal risk of associated morbidity. PMID:24666458

A Combination Therapy of JO-I and Chemotherapy in Ovarian Cancer Models

DTIC Science & Technology

2013-10-01

which consists of a 3PAR storage backend and is sharing data via a highly available NetApp storage gateway and 2 high throughput commodity storage...Environment is configured as self- service Enterprise cloud and currently hosts more than 700 virtual machines. The network infrastructure consists of...technology infrastructure and information system applications designed to integrate, automate, and standardize operations. These systems fuse state of

Subharmonic Imaging and Pressure Estimation for Monitoring Neoadjuvant Chemotherapy

DTIC Science & Technology

2014-09-01

and therapy response [10]. However, the level of IFP has been shown to predict disease free survival for cervix cancer (34% disease free survival...p. 1951-1961. 11. Milosevic M, et al., Interstitial fluid pressure predicts survival in patients with cervix cancer independent of clinical...12b. DISTRIBUTION CODE 13. ABSTRACT (Maximum 200 Words) Neoadjuvant chemotherapy is currently the standard of care for locally advanced breast cancer

Diagnostics and Treatment of Hepatocellular Carcinoma in 2016: Standards and Developments

PubMed Central

Trojan, Jörg; Zangos, Stephan; Schnitzbauer, Andreas A.

2016-01-01

Background Hepatocellular carcinoma (HCC) is a frequent complication of liver cirrhosis. Worldwide, HCC is one of the most common cancers, with a rising incidence. Methods A selective literature search was conducted, taking into account current studies, reviews, meta-analyses, and guidelines. Results The diagnosis is established either non-invasively by dynamic imaging, showing a typical contrast enhancement and wash-out, or histopathologically. Pathological diagnosis of HCC is recommended for all atypical nodules in patients with cirrhosis and for those in non-cirrhotic patients. Tumor therapy as well as treatment of the underlying chronic liver disease and/or preservation of liver function are important for the management of patients with HCC. Standard stage-adapted treatments are based on the widely applied Barcelona Clinic Liver Cancer staging system including liver resection and transplantation, interventional treatments such as thermal ablation and transarterial therapies, and systemic treatment with the tyrosine kinase inhibitor sorafenib. After failure of sorafenib, anti-angiogenic drugs, MET inhibitors, and immunotherapeutics are currently under advanced clinical investigation. Conclusion Treatment of HCC is multidisciplinary and therefore requires a close cooperation between various disciplines such as hepatology, visceral surgery, radiology, and oncology to achieve the best outcome depending on the tumor stage and degree of liver function impairment. PMID:27413729

Current Therapeutic Strategies for Adipose Tissue Defects/Repair Using Engineered Biomaterials and Biomolecule Formulations.

PubMed

Mahoney, Christopher M; Imbarlina, Cayla; Yates, Cecelia C; Marra, Kacey G

2018-01-01

Tissue engineered scaffolds for adipose restoration/repair has significantly evolved in recent years. Patients requiring soft tissue reconstruction, caused by defects or pathology, require biomaterials that will restore void volume with new functional tissue. The gold standard of autologous fat grafting (AFG) is not a reliable option. This review focuses on the latest therapeutic strategies for the treatment of adipose tissue defects using biomolecule formulations and delivery, and specifically engineered biomaterials. Additionally, the clinical need for reliable off-the-shelf therapies, animal models, and challenges facing current technologies are discussed.

A multicentre randomised controlled trial of the use of continuous positive airway pressure and non-invasive positive pressure ventilation in the early treatment of patients presenting to the emergency department with severe acute cardiogenic pulmonary oedema: the 3CPO trial.

PubMed

Gray, A J; Goodacre, S; Newby, D E; Masson, M A; Sampson, F; Dixon, S; Crane, S; Elliott, M; Nicholl, J

2009-07-01

To determine whether non-invasive ventilation reduces mortality and whether there are important differences in outcome by treatment modality. Multicentre open prospective randomised controlled trial. Patients presenting with severe acute cardiogenic pulmonary oedema in 26 emergency departments in the UK. Inclusion criteria were age > 16 years, clinical diagnosis of acute cardiogenic pulmonary oedema, pulmonary oedema on chest radiograph, respiratory rate > 20 breaths per minute, and arterial hydrogen ion concentration > 45 nmol/l (pH < 7.35). Patients were randomised to standard oxygen therapy, continuous positive airway pressure (CPAP) (5-15 cmH2O) or non-invasive positive pressure ventilation (NIPPV) (inspiratory pressure 8-20 cmH2O, expiratory pressure 4-10 cmH2O) on a 1:1:1 basis for a minimum of 2 hours. The primary end point for the comparison between NIPPV or CPAP and standard therapy was 7-day mortality. The composite primary end point for the comparison of NIPPV and CPAP was 7-day mortality and tracheal intubation rate. Secondary end points were breathlessness, physiological variables, intubation rate, length of hospital stay and critical care admission rate. Economic evaluation took the form of a cost-utility analysis, taken from an NHS (and personal social services) perspective. In total, 1069 patients [mean age 78 (SD 10) years; 43% male] were recruited to standard therapy (n = 367), CPAP [n = 346; mean 10 (SD 4) cmH2O] or NIPPV [n = 356; mean 14 (SD 5)/7 (SD 2) cmH2O]. There was no difference in 7-day mortality for standard oxygen therapy (9.8%) and non-invasive ventilation (9.5%; p = 0.87). The combined end point of 7-day death and intubation rate was similar, irrespective of non-invasive ventilation modality (CPAP 11.7% versus NIPPV 11.1%; p = 0.81). Compared with standard therapy, non-invasive ventilation was associated with greater reductions (treatment difference, 95% confidence intervals) in breathlessness (visual analogue scale score 0.7, 0.2-1.3; p = 0.008) and heart rate (4/min, 1-6; p = 0.004) and improvement in acidosis (pH 0.03, 0.02-0.04; p < 0.001) and hypercapnia (0.7 kPa, 0.4-0.9; p < 0.001) at 1 hour. There were no treatment-related adverse events or differences in other secondary outcomes such as myocardial infarction rate, length of hospital stay, critical care admission rate and requirement for endotracheal intubation. Economic evaluation showed that mean costs and QALYs up to 6 months were 3023 pounds and 0.202 for standard therapy, 3224 pounds and 0.213 for CPAP, and 3208 pounds and 0.210 for NIPPV. Modelling of lifetime costs and QALYs produced values of 15,764 pounds and 1.597 for standard therapy, 17,525 pounds and 1.841 for CPAP, and 17,021 pounds and 1.707 for NIPPV. These results suggest that both CPAP and NIPPV accrue more QALYs but at higher cost than standard therapy. However, these estimates are subject to substantial uncertainty. Non-invasive ventilatory support delivered by either CPAP or NIPPV safely provides earlier improvement and resolution of breathlessness, respiratory distress and metabolic abnormality. However, this does not translate into improved short- or longer-term survival. We recommend that CPAP or NIPPV should be considered as adjunctive therapy in patients with severe acute cardiogenic pulmonary oedema in the presence of severe respiratory distress or when there is a failure to improve with pharmacological therapy. Current Controlled Trials ISRCTN07448447.

Child-Focused and Context-Focused Behaviors of Physical and Occupational Therapists during Treatment of Young Children with Cerebral Palsy.

PubMed

Kruijsen-Terpstra, Anne J A; Ellens, Mariëlle; Ketelaar, Marjolijn; Verschuren, Olaf; Di Rezze, Briano; Gorter, Jan Willem; Visser-Meily, Anne M A; Jongmans, Marian J

2016-11-01

To (1) describe the child- and context-focused behaviors of physical and occupational therapists, and (2) compare the behaviors of therapists in a standard therapy session with those of therapists trained to deliver child- and context-focused services. Videos of 49 therapy sessions provided by 36 therapists were analyzed using the intervention domains of the Paediatric Rehabilitation Observational measure of Fidelity (PROF) to examine the therapeutic behaviors of physical and occupational therapists with young children with cerebral palsy (CP) (24 to 48 months) in a Dutch rehabilitation setting. The PROF ratings of 18 standard therapy sessions were compared with the ratings of 16 child- and 15 context-focused therapy sessions. Therapists who provided standard therapy demonstrated a mix of child- and context-focused behaviors. PROF ratings indicated fewer child- and context-focused behaviors during standard therapy sessions compared with sessions where therapists were instructed to use either child- or context-focused behaviors. A sample of Dutch physical and occupational therapists of young children with CP demonstrated a mix of child- and context-focused therapy behaviors during standard therapy. Further research is recommended on clinical reasoning and the effect of setting to better understand therapists' use of child- and context-focused behaviors during therapy sessions.

Standards of care issues with anticoagulation in real-world populations.

PubMed

2015-01-01

Current guidelines recommend anticoagulants for reducing the risk of stroke in appropriate patients with nonvalvular atrial fibrillation (NVAF) and for the acute treatment of venous thromboembolism (VTE) and the prevention of recurrent VTE. Warfarin is the standard of care for both NVAF and VTE, yet International Normalized Ratio (INR) control remains suboptimal, even in the clinical trial setting. Maintaining INR within the recommended therapeutic range is associated with better outcomes in these distinct populations. In VTE, high rates of recurrence have been reported during the first few weeks of treatment, emphasizing the importance of surveillance during this time and of early optimization of anticoagulation therapy. The NVAF population tends to have more comorbidities and requires longer-term therapy. It is important to keep in mind that real-world patient populations are more complex than those in controlled studies. Patients with multiple comorbidities are particularly challenging, and physicians may focus on clinically urgent issues rather than anticoagulation optimization. Despite the many complexities associated with the use of warfarin, it remains a mainstay of anticoagulation therapy. Aligning financial incentives and improving care coordination are important factors in moving toward better outcomes for patients who need anticoagulation therapy. The increased focus on value-based care and evolving approaches to patient treatment could lead more physicians and payers to consider alternatives to warfarin, including the use of novel oral anticoagulants.

Wound Healing of Cutaneous Sulfur Mustard Injuries

PubMed Central

Graham, John S.; Chilcott, Robert P.; Rice, Paul; Milner, Stephen M.; Hurst, Charles G.; Maliner, Beverly I.

2005-01-01

Sulfur mustard is an alkylating chemical warfare agent that primarily affects the eyes, skin, and airways. Sulfur mustard injuries can take several months to heal, necessitate lengthy hospitalizations, and result in significant cosmetic and/or functional deficits. Historically, blister aspiration and/or deroofing (epidermal removal), physical debridement, irrigation, topical antibiotics, and sterile dressings have been the main courses of action in the medical management of cutaneous sulfur mustard injuries. Current treatment strategy consists of symptomatic management and is designed to relieve symptoms, prevent infections, and promote healing. There are currently no standardized or optimized methods of casualty management that prevent or minimize deficits and provide for speedy wound healing. Several laboratories are actively searching for improved therapies for cutaneous vesicant injury, with the aim of returning damaged skin to optimal appearance and normal function in the shortest time. Improved treatment will result in a better cosmetic and functional outcome for the patient, and will enable the casualty to return to normal activities sooner. This editorial gives brief overviews of sulfur mustard use, its toxicity, concepts for medical countermeasures, current treatments, and strategies for the development of improved therapies. PMID:16921406

[Impact of early benefit assessment on patients with epilepsy in Germany: Current healthcare provision and therapeutic needs].

PubMed

Strzelczyk, A; Hamer, H M

2016-04-01

Epilepsy is one of the most common chronic neurological diseases and represents a significant burden for patients, their families and society. In more than 75 % of patients anticonvulsant therapy consists of valproate, carbamazepine, lamotrigine or levetiracetam. There is a need for polytherapy in drug-refractory patients and they suffer from negative effects on quality of life and employment that is associated with high indirect costs. To allow a comprehensive treatment in this patient group, access to new anticonvulsants with novel modes of action is needed; however, all applications for new antiepileptic drugs failed to prove added benefits during the Pharmaceutical Market Restructuring Act (AMNOG) in Germany. One of the main reasons is the mandatory definition of a standard comparative therapy. It remains unclear whether there will be studies in the future which will fulfill the requirements of the current version of AMNOG. Observational studies after approval and marketing of new antiepileptic drugs could be better alternatives to prove added benefits for individual patients in the current German healthcare system.

Pharmacotherapeutic options for treating Staphylococcus aureus bacteremia.

PubMed

Gudiol, Carlota; Cuervo, Guillermo; Shaw, Evelyn; Pujol, Miquel; Carratalà, Jordi

2017-12-01

Case-fatality rates for Staphylococcus aureus bacteremia (SAB) remain unacceptably high and have improved only modestly in recent decades. Treatment of SAB is still a clinical challenge, especially if methicillin-resistant strains are involved. New drugs with anti-staphylococcal activity are currently available, and their role as alternatives to standard therapies is being investigated. Areas covered: In this review, we give an update of the current available antibiotics for the treatment of SAB. We provide information regarding the pharmacological characteristics, the accepted indications, and the most important adverse events of the old and new anti-staphylococcal agents, as well as the existing evidence on their use for the treatment of SAB. Expert opinion: The management of patients with SAB is very complex and needs a multidisciplinary approach. There are currently new available options for the treatment of methicillin-resistant SAB. However, more data from clinical trials are needed to assign specific roles to each antibiotic and to include them in the new antibacterial armamentarium. The role of combination therapy for the treatment of increasingly complex patients with SAB deserves thorough investigation.

The cognitive treatment components and therapies of cognitive behavioral therapy for insomnia: A systematic review.

PubMed

Jansson-Fröjmark, Markus; Norell-Clarke, Annika

2018-06-07

Since the beginning of the twenty-first century, there has been an increased focus on developing and testing cognitive components and therapies for insomnia disorder. The aim of the current review was thus to describe and review the efficacy of cognitive components and therapies for insomnia. A systematic review was conducted on 32 studies (N = 1455 subjects) identified through database searches. Criteria for inclusion required that each study constituted a report of outcome from a cognitive component or therapy, that the study had a group protocol, adult participants with diagnosed insomnia or undiagnosed insomnia symptoms or reported poor sleep, and that the study was published until and including 2016 in English. Each study was systematically reviewed with a standard coding sheet. Several cognitive components, a multi-component cognitive program, and cognitive therapy were identified. It is concluded that there is support for paradoxical intention and cognitive therapy. There are also other cognitive interventions that appears promising, such as cognitive refocusing and behavioral experiments. For most interventions, the study quality was rated as low to moderate. We conclude that several cognitive treatment components and therapies can be viewed as efficacious or promising interventions for patients with insomnia disorder. Methodologically stronger studies are, however, warranted. Copyright © 2018 Elsevier Ltd. All rights reserved.

Retrospective study of orthovoltage radiation therapy for nasal tumors in 42 dogs.

PubMed

Northrup, N C; Etue, S M; Ruslander, D M; Rassnick, K M; Hutto, D L; Bengtson, A; Rand, W; Moore, A S

2001-01-01

Megavoltage radiation therapy currently is the standard of care for dogs with nasal tumors. Some studies report that surgery and adjunctive orthovoltage radiation therapy result in longer control of these tumors than does megavoltage radiation therapy alone. This study reports less effective control of nasal tumors in dogs treated with surgery and orthovoltage radiation than previously observed, supporting the superiority of megavoltage radiation therapy for these tumors. In addition, this study suggests 2 new prognostic indicators for dogs with nasal tumors and describes toxicity associated with surgery and orthovoltage therapy. Forty-two dogs with nasal tumors were treated with surgical cytoreduction and 48 Gy orthovoltage radiation therapy administered in twelve 4-Gy fractions. Median survival was 7.4 months. One- and 2-year survival rates were 37% and 17%, respectively. Dogs with facial deformity had shorter survival than those without deformity (P = .005). Dogs with resolution of clinical signs after treatment had longer survival than those with chronic nasal signs (P = .0001). Acute radiation toxicity was moderate to severe for skin and eye and negligible for oral mucosa. Toxicity healed within 1 month after radiation therapy. Late toxicity was mild, but 70% of evaluable dogs experienced persistent ocular signs. Only 39% of dogs achieved a disease-free period.

Diabetic Macular Edema: Current Understanding, Pharmacologic Treatment Options, and Developing Therapies.

PubMed

Miller, Kevin; Fortun, Jorge A

2018-01-01

Diabetic retinopathy and diabetic macular edema comprise a major source of visual disability throughout the developed world. The etiology and pathogenesis of macular edema is intricate and multifactorial, in which the hyperglycemic state in diabetes induces a microangiopathy. Through several inflammatory and vasogenic mediators, including vascular endothelial growth factor (VEGF) upregulation and inflammatory cytokines and chemokines, pathologic changes are induced in the vascular endothelium triggering breakdown of the blood retinal barrier, causing extravasation of fluid into the extracellular space and manifesting clinically as macular edema, resulting in visual loss. The advent of medications targeting the VEGF pathway has led to great clinical improvements compared with the previous standard of care of laser therapy alone, as shown in studies such as RISE, RIDE, VIVID, VISTA, and DRCR. However, analyses have shown that many patients have inadequate response or are nonresponders to anti-VEGF therapy, demonstrating the need for additional therapies to more comprehensively treat this disease. Although corticosteroid treatments and implants have demonstrated some efficacy in adjunctive and supplemental treatment, the need to more adequately treat macular edema remains. Our knowledge of diabetic macular edema continues to grow, leading to new currently available and emerging pharmacotherapies to further enhance our treatment and restore vision in those affected by diabetic macular edema. This review will discuss the pathogenesis of diabetic macular edema and the pharmacologic therapies available for its treatment, including anti-VEGF, steroids, and newer therapies still in development, such as angiopoietin antagonists, Tie2 agonists, kallikrein inhibitors, interleukin inhibitors, and others. Copyright 2018 Asia-Pacific Academy of Ophthalmology.

Medical Therapy of Active Ulcerative Colitis

PubMed Central

Bürger, Martin; Schmidt, Carsten; Teich, Niels; Stallmach, Andreas

2015-01-01

Summary Background Medical therapy of mild and moderate ulcerative colitis (UC) of any extent is evidence-based and standardized by national and international guidelines. However, patients with steroid-refractory UC still represent a challenge. Methods A literature search using PubMed (search terms: ulcerative colitis, therapy, new, 1-2008-2015) resulted in 821 publications. For the current article, 88 citations were extracted including 36 randomized controlled studies, 18 reviews, and 8 meta-analyses. Results In steroid-refractory UC, early intensive therapy using anti-tumor necrosis factor (TNF) antibodies or the calcineurin inhibitors cyclosporine and tacrolimus is indicated in any case to prevent progression to a toxic megacolon and/or to avoid proctocolectomy. In patients with chronic disease activity, treatment with anti-TNF antibodies has a higher level of evidence than azathioprine therapy and should therefore be preferred. However, there is a subgroup of UC patients who may achieve prolonged steroid-free remission on azathioprine monotherapy. The importance of vedolizumab, a newly registered inhibiting antibody against integrin, has not yet been fully clarified since direct comparison studies are lacking, in particular in relation to anti-TNF antibodies. Conclusion There is a great need for additional innovative therapies, especially in cases of primary non-response or secondary loss of response to anti-TNF antibodies. New small molecules (Janus kinase inhibitors) are promising with an acceptable safety profile and efficacy in UC. Further, strategies that target the intestinal microbiome are currently considered for patients with active or relapsing UC, and may in the future open up new therapeutic options. PMID:26557831

The rise of genomic profiling in ovarian cancer

PubMed Central

Previs, Rebecca A.; Sood, Anil K.; Mills, Gordon B.; Westin, Shannon N.

2017-01-01

Introduction Next-generation sequencing and advances in ‘omics technology have rapidly increased our understanding of the molecular landscape of epithelial ovarian cancers. Areas covered Once characterized only by histologic appearance and clinical behavior, we now understand many of the molecular phenotypes that underlie the different ovarian cancer subtypes. While the current approach to treatment involves standard cytotoxic therapies after cytoreductive surgery for all ovarian cancers regardless of histologic or molecular characteristics, focus has shifted beyond a ‘one size fits all’ approach to ovarian cancer. Expert commentary Genomic profiling offers potentially ‘actionable’ opportunities for development of targeted therapies and a more individualized approach to treatment with concomitant improved outcomes and decreased toxicity. PMID:27828713

Small Molecule Inhibitors in Acute Myeloid Leukemia: From the Bench to the Clinic

PubMed Central

Al-Hussaini, Muneera; DiPersio, John F.

2014-01-01

Many patients with acute myeloid leukemia (AML) will eventually develop refractory or relapsed disease. In the absence of standard therapy for this population, there is currently an urgent unmet need for novel therapeutic agents. Targeted therapy with small molecule inhibitors (SMIs) represents a new therapeutic intervention that has been successful for the treatment of multiple tumors (e.g., gastrointestinal stromal tumors, chronic myelogenous leukemia). Hence, there has been great interest in generating selective small molecule inhibitors targeting critical pathways of proliferation and survival in AML. This review highlights a selective group of intriguing therapeutic agents and their presumed targets in both preclinical models and in early human clinical trials. PMID:25025370

[Update on therapy of chronic heart failure. Innovations and studies from last year].

PubMed

Ewen, Sebastian; Linicus, Y; Böhm, M

2015-12-01

Chronic heart failure is one of the most common chronic diseases worldwide with increasing prevalence and incidence. Due to the high morbidity and mortality a standardized and evidence-based therapy is crucial. The present review article gives an overview about the innovations in 2014 based on the current guidelines of the European Society of Cardiology. First, improvements in established medication regimens regarding beta blockers and mineralocorticoid receptor antagonists as well as treatment options for heart rate reduction will be explained. Second, new pharmacological developments, such as angiotensin receptor neprilysin inhibition will be discussed. Finally, new insights into common comorbidities of patients with chronic heart failure, such as atrial fibrillation and hyperkalemia will be presented.

BRAF inhibitors: the current and the future.

PubMed

Zhang, Weijiang

2015-08-01

The introduction of BRAF inhibitors (BRAFi), vemurafenib and dabrafenib, revolutionized BRAFV600-mutated metastatic melanoma treatment with improved response rate and overall survival compared to standard chemotherapy. However, the mechanism related cutaneous toxicity remains a concern. In addition, intrinsic and acquired resistance remain the key challenges in BRAFi therapy. Extensive efforts to elucidate the mechanisms have led to an improved understanding of disease biology and resulted in exploration of multiple new therapeutic options. While the future looks bright with multiple new therapeutic strategies in exploration and possible new generations of BRAFi, there are questions remaining to be answered to enable more efficient use of BRAFi in cancer therapy. Copyright © 2015 Elsevier Ltd. All rights reserved.

Dawn of ocular gene therapy: implications for molecular diagnosis in retinal disease

PubMed Central

Jacques, ZANEVELD; Feng, WANG; Xia, WANG; Rui, CHEN

2013-01-01

Personalized medicine aims to utilize genomic information about patients to tailor treatment. Gene replacement therapy for rare genetic disorders is perhaps the most extreme form of personalized medicine, in that the patients’ genome wholly determines their treatment regimen. Gene therapy for retinal disorders is poised to become a clinical reality. The eye is an optimal site for gene therapy due to the relative ease of precise vector delivery, immune system isolation, and availability for monitoring of any potential damage or side effects. Due to these advantages, clinical trials for gene therapy of retinal diseases are currently underway. A necessary precursor to such gene therapies is accurate molecular diagnosis of the mutation(s) underlying disease. In this review, we discuss the application of Next Generation Sequencing (NGS) to obtain such a diagnosis and identify disease causing genes, using retinal disorders as a case study. After reviewing ocular gene therapy, we discuss the application of NGS to the identification of novel Mendelian disease genes. We then compare current, array based mutation detection methods against next NGS-based methods in three retinal diseases: Leber’s Congenital Amaurosis, Retinitis Pigmentosa, and Stargardt’s disease. We conclude that next-generation sequencing based diagnosis offers several advantages over array based methods, including a higher rate of successful diagnosis and the ability to more deeply and efficiently assay a broad spectrum of mutations. However, the relative difficulty of interpreting sequence results and the development of standardized, reliable bioinformatic tools remain outstanding concerns. In this review, recent advances NGS based molecular diagnoses are discussed, as well as their implications for the development of personalized medicine. PMID:23393028

How does routinely delivered cognitive-behavioural therapy for gambling disorder compare to "gold standard" clinical trial?

PubMed

Smith, David P; Fairweather-Schmidt, A Kate; Harvey, Peter W; Battersby, Malcolm W

2018-03-01

Currently, it is unknown whether treatment outcomes derived from randomized controlled trials (RCTs) of cognitive-behavioural therapy (CBT) for problem gamblers still hold when applied to patients seen in routine practice. Thus, data from an RCT of cognitive therapy versus exposure therapy for problem gambling versus patients of a gambling help service were compared. Assessments of problem gambling severity, psychosocial impairment, and alcohol use were undertaken at baseline and post-treatment and evaluated within a counterfactual framework. Findings showed that the contrast between routine CBT for pokies and horse betting had a significant effect, indicative of a 62% lower gambling urge score if routine CBT recipients had all been horse/track betters opposed to gambling with "pokies." However, the majority of contrasts indicated therapeutic outcomes achieved in routine CBT treatments were of equivalent robustness relative to RCT conditions. The present findings infer routine practice treatment outcomes are as efficacious as those generated in RCT contexts. Copyright © 2017 John Wiley & Sons, Ltd.

Triptorelin embonate: a 6-month formulation for prostate cancer.

PubMed

Whelan, Peter

2010-12-01

Luteinizing hormone releasing hormone (LH RH) agonists are the major agent for androgen deprivation therapy in advanced and metastatic prostate cancer. They also have a role in endometriosis, uterine fibroids and central precocious puberty. Triptorelin embonate 22.5 mg is a new, sustained-release, 6-month formulation of an LH RH agonist. It possesses longer duration of action than the current standard 3-month preparation and appears to have similar efficacy and side effects. The use of LH RH agonists for androgen deprivation in prostate cancer has increased considerably in the last 20 years. Recent work has shown that some of this usage has constituted overtreatment and it is within these newer paradigms of therapy that the new 6-month preparation is situated. The new 6-month LH RH preparation - triptorelin embonate - will be of help in several key areas of therapy for prostate cancer, notably as an adjunct to radiation therapy and chemotherapy. It possesses a similar effect, but with fewer side effects, than those that are now commonly available.

Narrowing of the Coronary Sinus: A Device-Based Therapy for Persistent Angina Pectoris.

PubMed

Konigstein, Maayan; Verheye, Stefan; Jolicœur, E Marc; Banai, Shmuel

2016-01-01

Alongside the remarkable advances in medical and invasive therapies for the treatment of ischemic heart disease, an increasing number of patients with advanced coronary artery disease unsuitable for revascularization continue to suffer from angina pectoris despite optimal medical therapy. Patients with chronic angina have poor quality of life and increased levels of anxiety and depression. A considerable number of innovative therapeutic modalities for the treatment of chronic angina have been investigated over the years; however, none of these therapeutic options has become a standard of care, and none are widely utilized. Current treatment options for refractory angina focus on medical therapy and secondary risk factor modification. Interventions to create increased pressure in the coronary sinus may alleviate myocardial ischemia by forcing redistribution of coronary blood flow from the less ischemic subepicardium to the more ischemic subendocardium, thus relieving symptoms of ischemia. Percutaneous, transvenous implantation of a balloon expandable, hourglass-shaped, stainless steel mesh in the coronary sinus to create a fixed focal narrowing and to increase backwards pressure, may serve as a new device-based therapy destined for the treatment of refractory angina pectoris.

Mixed methods research in music therapy research.

PubMed

Bradt, Joke; Burns, Debra S; Creswell, John W

2013-01-01

Music therapists have an ethical and professional responsibility to provide the highest quality care possible to their patients. Much of the time, high quality care is guided by evidence-based practice standards that integrate the most current, available research in making decisions. Accordingly, music therapists need research that integrates multiple ways of knowing and forms of evidence. Mixed methods research holds great promise for facilitating such integration. At this time, there have not been any methodological articles published on mixed methods research in music therapy. The purpose of this article is to introduce mixed methods research as an approach to address research questions relevant to music therapy practice. This article describes the core characteristics of mixed methods research, considers paradigmatic issues related to this research approach, articulates major challenges in conducting mixed methods research, illustrates four basic designs, and provides criteria for evaluating the quality of mixed methods articles using examples of mixed methods research from the music therapy literature. Mixed methods research offers unique opportunities for strengthening the evidence base in music therapy. Recommendations are provided to ensure rigorous implementation of this research approach.

How I manage ibrutinib-refractory chronic lymphocytic leukemia

PubMed Central

2017-01-01

The introduction of the Bruton tyrosine kinase (BTK) inhibitor ibrutinib has dramatically changed the management of chronic lymphocytic leukemia (CLL). Although responses have been durable in the majority of patients, relapses do occur, especially in the high-risk patient population. Most relapses occur as the result of acquired mutations in BTK and PLCG2, which may facilitate success with alternative targeted therapies. As outcomes after ibrutinib relapse have been reported to be poor, specific strategies are needed for this patient population. Here, I discuss the diagnosis and management of ibrutinib-refractory CLL. The focus will be on common clinical scenarios that can be mistaken for relapse and how to accurately determine which patients are relapsing. Because there is no established standard of care, I discuss currently available options for standard therapy and existing clinical data. I also discuss new agents with the potential to be effective in patients refractory to ibrutinib. Finally, I discuss strategies for long-term disease control in this patient population. PMID:28096090

Restraint of children with additional needs in motor vehicles: knowledge and challenges of paediatric occupational therapists in Victoria, Australia.

PubMed

Baker, Anne; Galvin, Jane; Vale, Lisa; Lindner, Helen

2012-02-01

This research project aimed to understand the challenges faced by occupational therapists when making recommendations regarding the restraint of children with additional needs in motor vehicles in Victoria, Australia. A cross-sectional survey design was used to explore current practice in relation to the prescription of motor vehicle restraints in Victoria, Australia. An electronic survey was sent to occupational therapists working with children aged from birth to 18 years in early intervention services, hospitals, schools, community services or private practice.   Challenges faced by occupational therapists related to a lack of knowledge of relevant standards and legal requirements, issues seating children with behavioural difficulties, families' inability to purchase recommended equipment and constraints as a result of funding issues. Further work is required to develop appropriate resources which support occupational therapists to make car seating recommendations for children with additional needs which comply with Australian legal requirements and standards. © 2011 The Authors. Australian Occupational Therapy Journal © 2011 Occupational Therapy Australia.

Medical nutrition therapy in adults with chronic kidney disease: integrating evidence and consensus into practice for the generalist registered dietitian nutritionist.

PubMed

Beto, Judith A; Ramirez, Wendy E; Bansal, Vinod K

2014-07-01

Chronic kidney disease is classified in stages 1 to 5 by the National Kidney Foundation's Kidney Disease Outcomes Quality Initiative depending on the level of renal function by glomerular filtration rate and, more recently, using further categorization depending on the level of glomerular filtration rate and albuminuria by the Kidney Disease Improving Global Outcomes initiative. Registered dietitian nutritionists can be reimbursed for medical nutrition therapy in chronic kidney disease stages 3 to 4 for specific clients under Center for Medicare and Medicaid Services coverage. This predialysis medical nutrition therapy counseling has been shown to both potentially delay progression to stage 5 (renal replacement therapy) and decrease first-year mortality after initiation of hemodialysis. The Joint Standards Task Force of the American Dietetic Association (now the Academy of Nutrition and Dietetics), the Renal Nutrition Dietetic Practice Group, and the National Kidney Foundation Council on Renal Nutrition collaboratively published 2009 Standards of Practice and Standards of Professional Performance for generalist, specialty, and advanced practice registered dietitian nutritionists in nephrology care. The purpose of this article is to provide an update on current recommendations for screening, diagnosis, and treatment of adults with chronic kidney disease for application in clinical practice for the generalist registered dietitian nutritionist using the evidence-based library of the Academy of Nutrition and Dietetics, published clinical practice guidelines (ie, National Kidney Foundation Council on Renal Nutrition, Renal Nutrition Dietetic Practice Group, Kidney Disease Outcomes Quality Initiative, and Kidney Disease Improving Global Outcomes), the Nutrition Care Process model, and peer-reviewed literature. Copyright © 2014 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.

Prevention of Left Ventricular Thrombus Formation and Systemic Embolism After Anterior Myocardial Infarction: A Systematic Literature Review.

PubMed

Bastiany, Alexandra; Grenier, Marie-Eve; Matteau, Alexis; Mansour, Samer; Daneault, Benoit; Potter, Brian J

2017-10-01

Anterior myocardial infarction (MI) with apical dysfunction is associated with an increased risk of left ventricular thrombus (LVT) formation and systemic embolism (SE). However, the role for prophylactic anticoagulation in current practice is a matter of debate. We conducted a systematic review of peer-reviewed original articles in either English or French on the benefit of combining anticoagulation with standard therapy for the prevention of LVT/SE after MI by searching PubMed, Ovid/MedLine/Embase, the Cochrane Library, and Google Scholar. Of 7382 identified records, 14 were retained for analysis. Nine articles addressed anticoagulation for patients not treated with percutaneous coronary intervention (PCI). Another 5 included at least some patients treated with PCI. Only 1 study specifically addressed exclusively a primary PCI population. Some studies showed a benefit for combining anticoagulation with standard therapy in patients not treated with PCI, but results were inconsistent. No evidence of benefit was reported when PCI patients were included and 1 study reported a signal for net harm. There was important interstudy heterogeneity and methodological limitations. Studies were likely individually underpowered. The available studies of LVT/SE prevention after MI lacked statistical power and are heterogeneous in terms of treatments, revascularization methods, background medical therapy, and study design. We conclude that there is presently no compelling evidence for or against combining anticoagulation with standard therapy for post-MI patients with apical dysfunction after primary PCI, and inconsistent evidence supporting prophylaxis after thrombolysis. An appropriately powered randomized trial is required to answer this clinically relevant question. Copyright © 2017 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

Cost-effectiveness of oral alitretinoin in patients with severe chronic hand eczema - a long-term analysis from a Swiss perspective

PubMed Central

2010-01-01

Background The impact on patients suffering from chronic hand eczema (CHE) is enormous, as no licensed systemic treatment option with proven efficacy for CHE is available. Alitretinoin is a novel agent which showed high clinical efficacy in patients with severe, refractory CHE. We assessed the cost-effectiveness of alitretinoin for CHE patient treatment from a Swiss third party payer perspective. A further objective of this study was to determine the burden of disease in Switzerland. Methods A long-term Markov cohort simulation model was used to estimate direct medical costs (€) and clinical effectiveness (quality adjusted life years, QALYs) of treating severe CHE patients with alitretinoin. Comparison was against the standard treatment of supportive care (optimised emollient therapy). Information on response rates were derived from a randomized controlled clinical trial. Costs were considered from the perspective of the Swiss health system. Swiss epidemiological data was derived from official Swiss Statistic institutions. Results Annual costs of alitretinoin treatment accounted for €2'212. After a time horizon of 22.4 years, average remaining long-term costs accounted for €42'208 or €38'795 in the alitretinoin and the standard treatment arm, respectively. Compared with the standard therapy, the addition of alitretinoin yielded an average gain of 0.230 QALYs at the end of the simulation. Accordingly, the incremental cost-effectiveness ratio resulted in €14'816/QALY gained. These results were robust to changes in key model assumptions. Conclusion The therapy for CHE patients is currently insufficient. In our long-term model we identified the treatment with alitretinoin as a cost-effective alternative for the therapy of CHE patients in Switzerland. PMID:20579358

Challenges and Opportunities Faced by Biofield Practitioners in Global Health and Medicine: A White Paper

PubMed Central

King, Rauni Prittinen

2015-01-01

Biofield therapies (BTs) are increasingly employed in contemporary healthcare. In this white paper, we review specific challenges faced by biofield practitioners resulting from a lack of (1) a common scientific definition of BT; (2) common educational standards for BT training (including core competencies for clinical care); (3) collaborative team care education in complementary and alternative medicine (CAM) and in integrative health and medicine (IHM); (4) a focused agenda in BT research; and (5) standardized devices and scientifically validated mechanisms in biofield research. We present a description of BT and discuss its current status and challenges as an integrative healthcare discipline. To address the challenges cited and to enhance collaboration across disciplines, we propose (1) standardized biofield education that leads to professional licensure and (2) interprofessional education (IPE) competencies in BT training required for licensed healthcare practitioners and encouraged for other practitioners using these therapies. Lastly, we discuss opportunities for growth and a potential strategic agenda to achieve these goals. The Academy of Integrative Health and Medicine (AIHM) provides a unique forum to facilitate development of this emerging discipline, to facilitate IPE, and to further increase the availability of BT to patients. PMID:26665047

A Systematic Review and Meta-Analysis of the Efficacy of Cognitive Behavioral Therapy for the Management of Pediatric Migraine.

PubMed

Ng, Qin Xiang; Venkatanarayanan, Nandini; Kumar, Lakshmi

2017-03-01

Migraine headaches are common in children and adolescents. Current pharmacologic treatment options are limited despite the prevalence and debilitating effects of pediatric migraine. Cognitive behavioral therapy (CBT) is an evidence-based practice that focuses on the development of coping strategies and cognitive restructuring to alter the pain experience. Till date, no meta-analysis has been done to examine the use of CBT in pediatric migraine. Using the keywords (cognitive behavioral therapy OR cognitive behavior therapy OR cognitive behavioral therapy OR cognitive behavior therapy OR CBT) AND (headache OR migraine), a preliminary search on the PubMed and Ovid database yielded 3841 articles published in English between 1 Jan 1980 and 1 May 2016. Full articles were also reviewed for references of interest. After data extraction, 14 studies were included in the meta-analysis. The results of the meta-analysis well-support the clinical role of CBT in the management of pediatric migraine. The pooled odds ratios of clinically significant improvement, that is, 50% or greater headache activity reduction post-treatment and at follow-up (3 months or later) were OR 9.11 (95% CI: 5.01 to 16.58, P < .001) and OR 9.18 (95% CI: 5.69 to 14.81, P < .001) respectively, demonstrating significant clinical improvement with CBT as compared with wait-list control, placebo, or standard medication. Furthermore, the clinical improvement was stable, even at a 1-year follow-up as evident in some of the studies. There is good evidence that CBT is beneficial to children suffering from migraine, and may also augment the efficacy of standard medications such as amitriptyline. © 2016 American Headache Society.

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

PubMed Central

2013-01-01

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

Recruitment standards and practices in occupational therapy, 1900-1930.

PubMed

Colman, W

1990-08-01

Debate regarding recruitment standards and practices exemplifies various visions of practice that exist within a profession. In occupational therapy, early recruitment criteria provide an example of how the field's founders envisioned the professional practitioner. As occupational therapy grew in membership throughout the 1920s, that vision was challenged. This paper identifies and describes the recruitment ideas expressed by both the founders of occupational therapy and their challengers from 1900 to 1930 and suggests the influence of their ideas on recruitment standards.

End points for adjuvant therapy trials: has the time come to accept disease-free survival as a surrogate end point for overall survival?

PubMed

Gill, Sharlene; Sargent, Daniel

2006-06-01

The intent of adjuvant therapy is to eradicate micro-metastatic residual disease following curative resection with the goal of preventing or delaying recurrence. The time-honored standard for demonstrating efficacy of new adjuvant therapies is an improvement in overall survival (OS). This typically requires phase III trials of large sample size with lengthy follow-up. With the intent of reducing the cost and time of completing such trials, there is considerable interest in developing alternative or surrogate end points. A surrogate end point may be employed as a substitute to directly assess the effects of an intervention on an already accepted clinical end point such as mortality. When used judiciously, surrogate end points can accelerate the evaluation of new therapies, resulting in the more timely dissemination of effective therapies to patients. The current review provides a perspective on the suitability and validity of disease-free survival (DFS) as an alternative end point for OS. Criteria for establishing surrogacy and the advantages and limitations associated with the use of DFS as a primary end point in adjuvant clinical trials and as the basis for approval of new adjuvant therapies are discussed.

KIDNEY STONES: AN UPDATE ON CURRENT PHARMACOLOGICAL MANAGEMENT AND FUTURE DIRECTIONS

PubMed Central

Xu, Hongshi; Zisman, Anna L.; Coe, Fredric L.; Worcester, Elaine M.

2013-01-01

Introduction Kidney stones are a common problem worldwide with substantial morbidities and economic costs. Medical therapy reduces stone recurrence significantly. Much progress has been made in the last several decades in improving therapy of stone disease. Areas covered 1) effect of medical expulsive therapy on spontaneous stone passage, 2) pharmacotherapy in the prevention of stone recurrence, 3) future directions in the treatment of kidney stone disease. Expert Opinion fluid intake to promote urine volume of at least 2.5L each day is essential to prevent stone formation. Dietary recommendations should be adjusted based on individual metabolic abnormalities. Properly dosed thiazide treatment is the standard therapy for calcium stone formers with idiopathic hypercalciuria. Potassium alkali therapy is considered for hypocitraturia, but caution should be taken to prevent potential risk of calcium phosphate stone formation. For absorptive hyperoxaluria, low oxalate diet and increased dietary calcium intake are recommended. Pyridoxine has been shown effective in some cases of primary hyperoxaluria type I. Allopurinol is used in calcium oxalate stone formers with hyperuricosuria. Treatment of cystine stones remains challenging. Tiopronin can be used if urinary alkalinization and adequate fluid intake are insufficient. For struvite stones, complete surgical removal coupled with appropriate antibiotic therapy is necessary. PMID:23438422

Mapping the literature of occupational therapy.

PubMed Central

Reed, K L

1999-01-01

Occupational therapy, formally organized in the United States in 1917, is considered an allied health field. Mapping occupational therapy literature is part of a bibliometric project of the Medical Library Association's Nursing and Allied Health Resources Section's project for mapping the literature of allied health. Three core journals were selected from the years 1995 and 1996 and a determination was made of the extent to which the cited journal references were covered by standard indexing sources. Using Bradford's Law of Scattering three zones were created, each containing approximately one-third of the cited journal references. The results showed that three journals made up the first zone, 117 journals the second, and 657 the third. The most cited journal was the American Journal of Occupational Therapy. In the second zone, journals from twelve disciplines were identified. While MEDLINE provided the best overall indexing, the Cumulative Index to Nursing and Allied Health Literature (CINAHL) was the only database that indexed the three most cited journals plus nine of the currently active titles in occupational therapy. MEDLINE could improve its coverage of occupational therapy by indexing the journals of the British, Canadian, and Australian national associations. PMID:10427431

MicroRNA-Directed Cancer Therapies: Implications in Melanoma Intervention.

PubMed

Thyagarajan, Anita; Shaban, Ahmed; Sahu, Ravi Prakash

2018-01-01

Acquired tumor resistance to cancer therapies poses major challenges in the treatment of cancers including melanoma. Among several signaling pathways or factors that affect neocarcinogenesis, cancer progression, and therapies, altered microRNAs (miRNAs) expression has been identified as a crucial player in modulating the key pathways governing these events. While studies in the miRNA field have grown exponentially in the last decade, much remains to be discovered, particularly with respect to their roles in cancer therapies. Since immune and nonimmune signaling cascades prevail in cancers, identification and evaluation of miRNAs, their molecular mechanisms and cellular targets involved in the underlying development of cancers, and acquired therapeutic resistance would help in devising new strategies for the prognosis, treatment, and an early detection of recurrence. Importantly, in-depth validation of miRNA-targeted molecular events could lead to the development of accurate progression-risk biomarkers, improved effectiveness, and improved patient responses to standard therapies. The current review focuses on the roles of miRNAs with recent updates on regulated cell cycle and proliferation, immune responses, oncogenic/epigenetic signaling pathways, invasion, metastasis, and apoptosis, with broader attention paid to melanomagenesis and melanoma therapies. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

Stem Cell Therapy for the Central Nervous System in Lysosomal Storage Diseases.

PubMed

Siddiqi, Faez; Wolfe, John H

2016-10-01

Neurological diseases with genetic etiologies result in the loss or dysfunction of neural cells throughout the CNS. At present, few treatment options exist for the majority of neurogenetic diseases. Stem cell transplantation (SCT) into the CNS has the potential to be an effective treatment modality because progenitor cells may replace lost cells in the diseased brain, provide multiple trophic factors, or deliver missing proteins. This review focuses on the use of SCT in lysosomal storage diseases (LSDs), a large group of monogenic disorders with prominent CNS disease. In most patients the CNS disease results in intellectual disability that is refractory to current standard-of-care treatment. A large amount of preclinical work on brain-directed SCT has been performed in rodent LSD models. Cell types that have been used for direct delivery into the CNS include neural stem cells, embryonic and induced pluripotent stem cells, and mesenchymal stem cells. Hematopoietic stem cells have been an effective therapy for the CNS in a few LSDs and may be augmented by overexpression of the missing gene. Current barriers and potential strategies to improve SCT for translation into effective patient therapies are discussed.

Stress urinary incontinence in women: Current and emerging therapeutic options

PubMed Central

Shamout, Samer; Campeau, Lysanne

2017-01-01

Surgical management of stress urinary incontinence (SUI) is most commonly achieved by midurethral synthetic sling (MUS) insertion as a first-line surgical option. A great deal of research continues to evolve new management strategies to reach an optimal balance of high efficacy and minimal adverse events. This expert opinion review provides a brief and comprehensive discussion of recent advances and ongoing research in the management of SUI, with an emphasis on single-incision mini-slings, vaginal laser treatment, and cell-based therapy. It is based on data obtained from numerous published meta-analyses and original studies identified through literature search. Single-incision mini-slings appear equally effective initially compared with standard MUS (retropubic or transobturator) for the treatment of female SUI; however, this efficacy lacks durability evidence beyond one-year followup. There is a lack of sufficient clinical evidence to currently confirm long-term safety and effectiveness of cell-therapy and non-ablative vaginal laser therapy, besides suggestion of apparent initial safety. There are still significant challenges to overcome before widespread clinical practice of the latter two modalities. Future research should be aimed at identifying groups of patients who might benefit from these minimally invasive therapeutic options. PMID:28616118

How effective is ureteroscopy in the treatment of pediatric stone disease?

PubMed

Thomas, John C

2010-08-01

Pediatric ureteroscopy has been increasingly used to manage both ureteral and renal stones. Unfortunately, there are no current standardized recommendations when treating pediatric stone disease so the modality chosen is left to the treating surgeon. A review of the current literature on pediatric ureteroscopy was used to compile this article. For the purposes of this review, the majority of series include stones < or =1 cm. Ureteroscopy is considered to be first-line therapy in treating mid- to distal ureteral stones and is rapidly evolving as an acceptable first-line therapy for renal stones as well. Limitations do exist and include stone composition, location, size, as well as the unique anatomic challenges faced by pediatric urologists in terms of anomalous kidneys and/or reconstructed urinary tracts. In conclusion, ureteroscopy can be considered first-line therapy for mid- or distal ureteral stones, however, it shares a similar efficacy rate as extracorporeal shock wave lithotripsy for the treatment of renal calculi. There is a need for direct comparison in the literature of all modalities treating pediatric stone disease to facilitate guidelines that help treating surgeons choose the most efficacious modality offering the highest success rates with the lowest morbidity.

Internet use, misuse, and addiction in adolescents: current issues and challenges.

PubMed

Greydanus, Donald E; Greydanus, Megan M

2012-01-01

The Internet has revolutionized education and social communication in the 21st century. This article reviews the growing literature identifying a number of adolescents and young adults with a pathologically excessive Internet use leading to many potential consequences. Current research dilemmas in this area include that Internet addiction is a broad topic with no standard definition and no standard measurement tools. Management of youth with identified problematic Internet use or misuse centers on behavioral therapy and treatment of comorbidities. Pharmacologic approaches are limited at this time but are undergoing research, such as use of opioid antagonists and antidepressants in adults with pathological gambling. Efforts should be expanded on not only the education of all adolescents regarding the benefits but also the potential negative consequences of Internet use. It is vital that we do this for Generation Z, whereas Generation ALPHA will soon benefit or suffer from our efforts in this regard today.

Sports medicine and platelet-rich plasma: nonsurgical therapy.

PubMed

Grambart, Sean T

2015-01-01

A Cochrane Review was performed to assess the effects of platelet-rich therapies for treating musculoskeletal soft tissue injuries. Selection criteria were randomized and quasirandomized controlled trials (RCTs) that compared platelet-rich therapy with either placebo, autologous whole blood, dry needling, or no platelet-rich therapy for people with acute or chronic musculoskeletal soft tissue injuries. Primary outcomes were functional status, pain, and adverse effects. The investigators found 19 studies that compared platelet-rich therapy with placebo, autologous whole blood, dry needling, or no platelet-rich therapy. Disorders included rotator cuff tears (arthroscopic repair; 6 trials); shoulder impingement syndrome surgery (1 trial); elbow epicondylitis (3 trials); anterior cruciate ligament (ACL) reconstruction (4 trials), ACL reconstruction (donor graft site application; 2 trials), patellar tendinopathy (1 trial), Achilles tendinopathy (1 trial), and acute Achilles rupture surgical repair (1 trial). They further subdivided the studies based on type of treatment, including tendinopathies in which platelet-rich therapy injections were the main treatment (5 trials), and surgical augmentation procedures in which platelet-rich therapy was applied during surgery (14 trials). The conclusion was that there is currently insufficient evidence to support the use of platelet-rich therapy for treating musculoskeletal soft tissue injuries. Researchers contemplating RCTs should consider the coverage of currently ongoing trials when assessing the need for future RCTs on specific conditions. There is a need for standardization of PRP preparation methods. At this time, the use of PRP in foot and ankle surgery as an orthobiologic does not have an absolute indication. Many of the studies are lower evidence-based from surgical techniques. Several in vitro studies have shown that growth factors promote the regeneration of bone, cartilage, and tendons. More clinical studies are needed to evaluate the use of PRP as an orthobiologic. In the author’s opinion, PRP does have a role when conservative treatment has failed and the next treatment option is an invasive surgical procedure Copyright © 2015 Elsevier Inc. All rights reserved.

Cost-effectiveness of omalizumab add-on to standard-of-care therapy in patients with uncontrolled severe allergic asthma in a Brazilian healthcare setting.

PubMed

Suzuki, Cibele; Lopes da Silva, Nilceia; Kumar, Praveen; Pathak, Purnima; Ong, Siew Hwa

2017-08-01

Omalizumab add-on to standard-of-care therapy has proven to be efficacious in severe asthma patients for whom exacerbations cannot be controlled otherwise. Moreover, evidence from different healthcare settings suggests reduced healthcare resource utilization with omalizumab. Based on these findings, this study aimed to assess the cost-effectiveness of the addition of omalizumab to standard-of-care therapy in patients with uncontrolled severe allergic asthma in a Brazilian healthcare setting. A previously published Markov model was adapted using Brazil-specific unit costs to compare the costs and outcomes of the addition of omalizumab to standard-of-care therapy vs standard-of-care therapy alone. Model inputs were largely based on the eXpeRience study. Costs and health outcomes were calculated for lifetime-years and were annually discounted at 5%. Both one-way and probabilistic sensitivity analyses were performed. An additional cost of R$280,400 for 5.20 additional quality-adjusted life-years was estimated with the addition of omalizumab to standard-of-care therapy, resulting in an incremental cost-effectiveness ratio of R$53,890. One-way sensitivity analysis indicated that discount rates, standard-of-care therapy exacerbation rates, and exacerbation-related mortality rates had the largest impact on incremental cost-effectiveness ratios. Assumptions of lifetime treatment adherence and rate of future exacerbations, independent of previous events, might affect the findings. The lack of Brazilian patients in the eXpeRience study may affect the findings, although sample size and baseline characteristics suggest that the modeled population closely resembles Brazilian severe allergic asthma patients. Results indicate that omalizumab as an add-on therapy is more cost-effective than standard-of-care therapy alone for Brazilian patients with uncontrolled severe allergic asthma, based on the World Health Organization's cost-effectiveness threshold of up to 3-times the gross domestic product.

Preclinical Validation of Novel Fluorescently Labeled Compounds to Treat Neurodegenerative Hearing Loss

DTIC Science & Technology

2016-10-01

evaluated using 209, 639, and 1269 magnification. For repre- sentative documentation of the morphology of each specimen, the photographs were taken from the...Holmes SJ, Kaplan SL, Jubelirer DP, Stechenberg BW, Hirsh SK (1984) Prospective evaluation of hearing impairment as a sequela of acute bacterial...enters the field of gene therapy and human studies commence, the question arises whether audiograms e the current gold standard for the evaluation of

CONSENSUS TREATMENT PLANS FOR INDUCTION THERAPY OF NEWLY-DIAGNOSED PROLIFERATIVE LUPUS NEPHRITIS IN JUVENILE SYSTEMIC LUPUS ERYTHEMATOSUS

PubMed Central

Mina, Rina; von Scheven, Emily; Ardoin, Stacy P.; Eberhard, B. Anne; Punaro, Marilynn; Ilowite, Norman; Hsu, Joyce; Klein-Gitelman, Marisa; Moorthy, L. Nandini; Muscal, Eyal; Radhakrishna, Suhas M.; Wagner-Weiner, Linda; Adams, Matthew; Blier, Peter; Buckley, Lenore; Chalom, Elizabeth; Chédeville, Gaëlle; Eichenfield, Andrew; Fish, Natalya; Henrickson, Michael; Hersh, Aimee O.; Hollister, Roger; Jones, Olcay; Jung, Lawrence; Levy, Deborah; Lopez-Benitez, Jorge; McCurdy, Deborah; Miettunen, Paivi M.; Quintero-Del Rio, Ana I.; Rothman, Deborah; Rullo, Ornella; Ruth, Natasha; Schanberg, Laura E.; Silverman, Earl; Singer, Nora G.; Soep, Jennifer; MBBS, Reema Syed; Vogler, Larry B.; Yalcindag, Ali; Yildirim-Toruner, Cagri; Wallace, Carol A.; Brunner, Hermine I.

2012-01-01

Objective To formulate consensus treatment plans (CTPs) for induction therapy of newly-diagnosed proliferative lupus nephritis (LN) in juvenile systemic lupus erythematosus (jSLE). Methods A structured consensus formation process was employed by the members of the Childhood Arthritis and Rheumatology Research Alliance (CARRA) after considering the existing medical evidence and current treatment approaches. Results After an initial Delphi survey (response rate 70%), a 2-day consensus conference, and two follow-up Delphi surveys (response rates 63–79%), consensus was achieved for a limited set of CTPs addressing the induction therapy of proliferative LN. These CTPs were developed for prototypic patients defined by eligibility characteristics, and included immunosuppressive therapy with either mycophenolic acid orally twice per day, or intravenous cyclophosphamide once per month at standardized doses for six months. Additionally, the CTPs describe three options for standardized use of glucocorticoids; including a primarily oral, a mixed oral/intravenous, and a primarily intravenous regimen. There was consensus on measures of effectiveness and safety of the CTPs. The CTPs were well accepted by the pediatric rheumatology providers treating children with LN, and up to 300 children per year in North America are expected to be candidates for the treatment with the CTPs. Conclusion CTPs for induction therapy of proliferative LN in jSLE based on the available scientific evidence and pediatric rheumatology group experience have been developed. Consistent use of the CTPs may improve the prognosis of proliferative LN, and support the conduct of comparative effectiveness studies aimed at optimizing therapeutic strategies for proliferative LN in jSLE. PMID:22162255

Breast Cancer-Related Arm Lymphedema: Incidence Rates, Diagnostic Techniques, Optimal Management and Risk Reduction Strategies

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

Shah, Chirag; Vicini, Frank A., E-mail: fvicini@beaumont.edu

As more women survive breast cancer, long-term toxicities affecting their quality of life, such as lymphedema (LE) of the arm, gain importance. Although numerous studies have attempted to determine incidence rates, identify optimal diagnostic tests, enumerate efficacious treatment strategies and outline risk reduction guidelines for breast cancer-related lymphedema (BCRL), few groups have consistently agreed on any of these issues. As a result, standardized recommendations are still lacking. This review will summarize the latest data addressing all of these concerns in order to provide patients and health care providers with optimal, contemporary recommendations. Published incidence rates for BCRL vary substantially withmore » a range of 2-65% based on surgical technique, axillary sampling method, radiation therapy fields treated, and the use of chemotherapy. Newer clinical assessment tools can potentially identify BCRL in patients with subclinical disease with prospective data suggesting that early diagnosis and management with noninvasive therapy can lead to excellent outcomes. Multiple therapies exist with treatments defined by the severity of BCRL present. Currently, the standard of care for BCRL in patients with significant LE is complex decongestive physiotherapy (CDP). Contemporary data also suggest that a multidisciplinary approach to the management of BCRL should begin prior to definitive treatment for breast cancer employing patient-specific surgical, radiation therapy, and chemotherapy paradigms that limit risks. Further, prospective clinical assessments before and after treatment should be employed to diagnose subclinical disease. In those patients who require aggressive locoregional management, prophylactic therapies and the use of CDP can help reduce the long-term sequelae of BCRL.« less

An Update on the Role of Immunotherapy and Vaccine Strategies for Primary Brain Tumors.

PubMed

Neagu, Martha R; Reardon, David A

2015-11-01

Existing therapies for glioblastoma (GBM), the most common malignant primary brain tumor in adults, have fallen short of improving the dismal patient outcomes, with an average 14-16-month median overall survival. The biological complexity and adaptability of GBM, redundancy of dysregulated signaling pathways, and poor penetration of therapies through the blood-brain barrier contribute to poor therapeutic progress. The current standard of care for newly diagnosed GBM consists of maximal safe resection, followed by fractionated radiotherapy combined with concurrent temozolomide (TMZ) and 6-12 cycles of adjuvant TMZ. At progression, bevacizumab with or without additional chemotherapy is an option for salvage therapy. The recent FDA approval of sipuleucel-T for prostate cancer and ipilumimab, nivolumab, and pembrolizumab for select solid tumors and the ongoing trials showing clinical efficacy and response durability herald a new era of cancer treatment with the potential to change standard-of-care treatment across multiple cancers. The evaluation of various immunotherapeutics is advancing for GBM, putting into question the dogma of the CNS as an immuno-privileged site. While the field is yet young, both active immunotherapy involving vaccine strategies and cellular therapy as well as reversal of GBM-induced global immune-suppression through immune checkpoint blockade are showing promising results and revealing essential immunological insights regarding kinetics of the immune response, immune evasion, and correlative biomarkers. The future holds exciting promise in establishing new treatment options for GBM that harness the patients' own immune system by activating it with immune checkpoint inhibitors, providing specificity using vaccine therapy, and allowing for modulation and enhancement by combinatorial approaches.

Acute pancreatitis associated with pegylated interferon-alpha-2a therapy in chronic hepatitis C

PubMed Central

Choi, Jong Wook; Lee, June Sung; Paik, Woo Hyun; Song, Tae Jun; Kim, Jung Wook; Bae, Won Ki; Kim, Kyung-Ah; Kim, Jung Gon

2016-01-01

Chronic hepatitis C virus (HCV) infection is a major cause of liver cirrhosis and hepatocellular carcinoma. Combination therapy of pegylated interferon-alpha (PEG-IFN-α) and ribavirin (RBV) is a current standard treatment for chronic HCV infection in Korea, which has considerable adverse effects. Acute pancreatitis is a rare complication of PEG-IFN-α administration. We report a case of a 62-year-old female who experienced acute pancreatitis after 4 weeks of PEG-IFN-α-2a and RBV combination therapy for chronic HCV infection. The main cause of the acute pancreatitis in this case was probably PEG-IFN-α rather than RBV for several reasons. A few cases have been reported in which acute pancreatitis occurred during treatment with PEG-IFN-α-2b. This is the first report of acute pancreatitis associated with PEG-IFN-α-2a in Korea. PMID:27044768

Automatic Detection of Seizures with Applications

NASA Technical Reports Server (NTRS)

Olsen, Dale E.; Harris, John C.; Cutchis, Protagoras N.; Cristion, John A.; Lesser, Ronald P.; Webber, W. Robert S.

1993-01-01

There are an estimated two million people with epilepsy in the United States. Many of these people do not respond to anti-epileptic drug therapy. Two devices can be developed to assist in the treatment of epilepsy. The first is a microcomputer-based system designed to process massive amounts of electroencephalogram (EEG) data collected during long-term monitoring of patients for the purpose of diagnosing seizures, assessing the effectiveness of medical therapy, or selecting patients for epilepsy surgery. Such a device would select and display important EEG events. Currently many such events are missed. A second device could be implanted and would detect seizures and initiate therapy. Both of these devices require a reliable seizure detection algorithm. A new algorithm is described. It is believed to represent an improvement over existing seizure detection algorithms because better signal features were selected and better standardization methods were used.

Acute pancreatitis associated with pegylated interferon-alpha-2a therapy in chronic hepatitis C.

PubMed

Choi, Jong Wook; Lee, June Sung; Paik, Woo Hyun; Song, Tae Jun; Kim, Jung Wook; Bae, Won Ki; Kim, Kyung-Ah; Kim, Jung Gon

2016-03-01

Chronic hepatitis C virus (HCV) infection is a major cause of liver cirrhosis and hepatocellular carcinoma. Combination therapy of pegylated interferon-alpha (PEG-IFN-α) and ribavirin (RBV) is a current standard treatment for chronic HCV infection in Korea, which has considerable adverse effects. Acute pancreatitis is a rare complication of PEG-IFN-α administration. We report a case of a 62-year-old female who experienced acute pancreatitis after 4 weeks of PEG-IFN-α-2a and RBV combination therapy for chronic HCV infection. The main cause of the acute pancreatitis in this case was probably PEG-IFN-α rather than RBV for several reasons. A few cases have been reported in which acute pancreatitis occurred during treatment with PEG-IFN-α-2b. This is the first report of acute pancreatitis associated with PEG-IFN-α-2a in Korea.

Survey of Usual Practice: Dysphagia Therapy in Head & Neck Cancer Patients

PubMed Central

Krisciunas, Gintas P.; Sokoloff, William; Stepas, Katherine; Langmore, Susan E.

2012-01-01

There is no standardized dysphagia therapy for head and neck cancer patients and scant evidence to support any particular protocol, leaving institutions and individual speech language pathologists (SLPs) to determine their own protocols based on “typical” practices or anecdotal evidence. To gain an understanding of current usual practices, a national internet-based survey was developed and disseminated to SLPs who treat HNC patients. From a random sample of 4,000 ASHA SID 13 members, 1,931 fit the inclusion criteria, and 759 complete responses were recorded for a 39.3% response rate. Results were analyzed by institution type as well as by individual clinical experience. While some interesting trends emerged from the data, a lack of uniformity and consensus regarding best practices was apparent. This is undoubtedly due to a paucity of research adequately addressing the efficacy of any one therapy for dysphagia in the HNC population. PMID:22456699

Myocardial Viability: From Proof of Concept to Clinical Practice

PubMed Central

Tan, Timothy C.; Hsu, Chijen; Denniss, Alan Robert

2016-01-01

Ischaemic left ventricular (LV) dysfunction can arise from myocardial stunning, hibernation, or necrosis. Imaging modalities have become front-line methods in the assessment of viable myocardial tissue, with the aim to stratify patients into optimal treatment pathways. Initial studies, although favorable, lacked sufficient power and sample size to provide conclusive outcomes of viability assessment. Recent trials, including the STICH and HEART studies, have failed to confer prognostic benefits of revascularisation therapy over standard medical management in ischaemic cardiomyopathy. In lieu of these recent findings, assessment of myocardial viability therefore should not be the sole factor for therapy choice. Optimization of medical therapy is paramount, and physicians should feel comfortable in deferring coronary revascularisation in patients with coronary artery disease with reduced LV systolic function. Newer trials are currently underway and will hopefully provide a more complete understanding of the pathos and management of ischaemic cardiomyopathy. PMID:27313943

Update on primary head and neck mucosal melanoma

PubMed Central

López, Fernando; Rodrigo, Juan P.; Cardesa, Antonio; Triantafyllou, Asterios; Devaney, Kenneth O.; Mendenhall, William M.; Haigentz, Missak; Strojan, Primož; Pellitteri, Phillip K.; Bradford, Carol R.; Shaha, Ashok R.; Hunt, Jennifer L.; de Bree, Remco; Takes, Robert P.; Rinaldo, Alessandra; Ferlito, Alfio

2016-01-01

Primary mucosal melanomas (PMMs) of the head and neck are uncommon malignancies that arise mainly in the nasal cavity and paranasal sinuses, followed by the oral cavity. The mainstay of treatment is radical surgical resection followed by adjuvant radiotherapy in selected patients with high-risk features. Multimodality therapy has not been well studied and is not standardized. Adjuvant radiotherapy seems to improve locoregional control but does not improve overall survival (OS). Elective neck dissection is advocated in patients with oral PMM. Systemic therapy should be considered only for patients with metastatic or unresectable locoregional disease. Despite improvements in the field of surgery, radiotherapy, and systemic therapy, patients with PMM still face a very unfavorable prognosis (5-year disease-free survival [DFS] <20%) with high rates of locoregional recurrence and distant metastasis. The present review aims to summarize the current state of knowledge on the molecular biology, pathological diagnosis, and management of this disease. PMID:25242350

Idiopathic recurrent pericarditis as an immune-mediated disease: current insights into pathogenesis and emerging treatment options.

PubMed

Imazio, Massimo

2014-11-01

Idiopathic recurrent pericarditis affects 30-50% of patients with a previous attack of pericarditis. The etiopathogenesis is incompletely understood and most cases remain idiopathic with a presumed immune-mediated pathogenesis. The mainstay of therapy is aspirin or a nonsteroidal anti-inflammatory drug plus colchicine and the possible adjunct of a low-to-moderate dose of a corticosteroid in more difficult cases. Colchicine as an adjunct to anti-inflammatory therapy reduces by 50% the subsequent recurrent rate. For true refractory cases with failure of standard combination therapies, new and emerging options especially include human intravenous immunoglobulins and biological agents (i.e., anakinra). The outcome of idiopathic recurrent pericarditis is good with a negligible risk of developing constrictive pericarditis. Thus, it is important to reassure patients on their prognosis, explaining the nature of the disease and the likely course. Moreover, therapeutic choices should include less toxic agents and favor cheaper drugs whenever possible.

Biomarkers for the differentiation of sepsis and SIRS: the need for the standardisation of diagnostic studies.

PubMed

Hall, T C; Bilku, D K; Al-Leswas, D; Horst, C; Dennison, A R

2011-12-01

Sepsis is a leading cause of death in the critically ill patient. It is a heterogeneous disease and it is frequently difficult to make an unequivocal and expeditious diagnosis. The current 'gold standard' in diagnosing sepsis is the blood culture but this is only available after a significant time delay. Mortality rates from sepsis remain high, however, the introduction of sepsis care bundles in its management has produced significant improvements in patient outcomes. Central to goal-directed resuscitation is the timely and accurate diagnosis of sepsis. The rapid diagnosis and commencement of the appropriate therapies has been shown to reduce the mortality. Biomarkers are already used in clinical practice to aid other more traditional diagnostic tests. In the absence of an adequate gold standard to diagnose sepsis, there has been considerable and growing interest in trying to identify suitable biomarkers. There is currently an unmet need in the medical literature to communicate the importance of the challenges relating to the rapid diagnosis and implementation of goal-directed therapy in sepsis and the underlying concepts that are directing these investigations. This article reviews the more novel biomarkers investigated to differentiate systemic inflammatory response syndrome from sepsis. The biomarkers described reflect the difficulties in making evidence-based recommendations particularly when interpreting studies where the methodology is of poor quality and the results are conflicting. We are reminded of our responsibilities to ensure high quality and standardised study design as articulated by the STAndards for the Reporting of Diagnostic accuracy studies (STARD) initiative.

Low level laser therapy and hair regrowth: an evidence-based review.

PubMed

Zarei, Mina; Wikramanayake, Tongyu C; Falto-Aizpurua, Leyre; Schachner, Lawrence A; Jimenez, Joaquin J

2016-02-01

Despite the current treatment options for different types of alopecia, there is a need for more effective management options. Recently, low-level laser therapy (LLLT) was evaluated for stimulating hair growth. Here, we reviewed the current evidence on the LLLT effects with an evidence-based approach, focusing more on randomized controlled studies by critically evaluating them. In order to investigate whether in individuals presenting with hair loss (male pattern hair loss (MPHL), female pattern hair loss (FPHL), alopecia areata (AA), and chemotherapy-induced alopecia (CIA)) LLLT is effective for hair regrowth, several databases including PubMed, Google Scholar, Medline, Embase, and Cochrane Database were searched using the following keywords: Alopecia, Hair loss, Hair growth, Low level laser therapy, Low level light therapy, Low energy laser irradiation, and Photobiomodulation. From the searches, 21 relevant studies were summarized in this review including 2 in vitro, 7 animal, and 12 clinical studies. Among clinical studies, only five were randomized controlled trials (RCTs), which evaluated LLLT effect on male and female pattern hair loss. The RCTs were critically appraised using the created checklist according to the Critical Appraisal for Therapy Articles Worksheet created by the Center of Evidence-Based Medicine, Oxford. The results demonstrated that all the performed RCTs have moderate to high quality of evidence. However, only one out of five studies performed intention-to-treat analysis, and only another study reported the method of randomization and subsequent concealment of allocation clearly; all other studies did not include this very important information in their reports. None of these studies reported the treatment effect of factors such as number needed to treat. Based on this review on all the available evidence about effect of LLLT in alopecia, we found that the FDA-cleared LLLT devices are both safe and effective in patients with MPHL and FPHL who did not respond or were not tolerant to standard treatments. Future randomized controlled trials of LLLT are strongly encouraged to be conducted and reported according to the Consolidated Standards of Reporting Trials (CONSORT) statement to facilitate analysis and comparison.

Current evidence for the safety and efficacy of the bio-engineered dual therapy COMBO stent.

PubMed

Kalkman, Deborah N; Chandrasekhar, Jaya; de Winter, Robbert J; Mehran, Roxana

2018-06-01

The novel dual-therapy COMBO stent aims to promote vessel healing after percutaneous coronary intervention (PCI) in patients with coronary artery disease. The pro-healing technique consists of an anti-CD34+ antibody layer that attracts circulating endothelial progenitor cells (EPCs), which bind to the stent surface and allow rapid endothelialization by differentiation of the EPCs into normal endothelial cells. The COMBO stent combines this pro-healing technique with an abluminal drug elution of sirolimus. The promise of this dual-therapy stent is that it may safely allow a shortened duration of dual-antiplatelet therapy (DAPT) after stent placement. Moreover, with a mature endothelial layer, lower rates of in-stent restenosis may be expected. Clinical outcomes after COMBO stent implantation have been recently evaluated in both randomized trials and large, prospective, multicenter registries, showing low clinical event rates of in-stent restenosis and stent thrombosis. Randomized clinical trials (HARMONEE and RECOVERY) have demonstrated the non-inferiority of COMBO versus "first in class" second generation and newer generation drug-eluting stents. Safety and efficacy of 3 months of DAPT after COMBO stent placement in patients presenting with acute coronary syndrome has been evaluated in the large REDUCE randomized controlled trial, showing non-inferiority to standard duration of 12-month DAPT. In this review we provide an overview of the current pre-clinical and clinical evidence for the performance of the COMBO stent.

Early oral switch therapy in low-risk Staphylococcus aureus bloodstream infection (SABATO): study protocol for a randomized controlled trial.

PubMed

Kaasch, Achim J; Fätkenheuer, Gerd; Prinz-Langenohl, Reinhild; Paulus, Ursula; Hellmich, Martin; Weiß, Verena; Jung, Norma; Rieg, Siegbert; Kern, Winfried V; Seifert, Harald

2015-10-09

Current guidelines recommend that patients with Staphylococcus aureus bloodstream infection (SAB) are treated with long courses of intravenous antimicrobial therapy. This serves to avoid SAB-related complications such as relapses, local extension and distant metastatic foci. However, in certain clinical scenarios, the incidence of SAB-related complications is low. Patients with a low-risk for complications may thus benefit from an early switch to oral medication through earlier discharge and fewer complications of intravenous therapy. The major objective for the SABATO trial is to demonstrate that in patients with low-risk SAB a switch from intravenous to oral antimicrobial therapy (oral switch therapy, OST) is non-inferior to a conventional course of intravenous therapy (intravenous standard therapy, IST). The trial is designed as randomized, parallel-group, observer-blinded, clinical non-inferiority trial. The primary endpoint is the occurrence of a SAB-related complication (relapsing SAB, deep-seated infection, and attributable mortality) within 90 days. Secondary endpoints are the length of hospital stay; 14-day, 30-day, and 90-day mortality; and complications of intravenous therapy. Patients with SAB who have received 5 to 7 full days of adequate intravenous antimicrobial therapy are eligible. Main exclusion criteria are polymicrobial bloodstream infection, signs and symptoms of complicated SAB (deep-seated infection, hematogenous dissemination, septic shock, and prolonged bacteremia), the presence of a non-removable foreign body, and severe comorbidity. Patients will receive either OST or IST with a protocol-approved antimicrobial and are followed up for 90 days. Four hundred thirty patients will be randomized 1:1 in two study arms. Efficacy regarding incidence of SAB-related complications is tested sequentially with a non-inferiority margin of 10 and 5 percentage points. The SABATO trial assesses whether early oral switch therapy is safe and effective for patients with low-risk SAB. Regardless of the result, this pragmatic trial will strongly influence the standard of care in SAB. ClinicalTrials.gov NCT01792804 registered 13 February 2013; German Clinical trials register DRKS00004741 registered 4 October 2013, EudraCT 2013-000577-77 . First patient randomized on 20 December 2013.

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.

[Conservative therapy of cartilage defects of the upper ankle joint].

PubMed

Smolenski, U C; Best, N; Bocker, B

2008-03-01

Cartilage defects of the upper ankle joint reflect the problem that great force is transmitted and balanced out over a relatively small surface area. As a pathophysiological factor, cartilage-bone contusions play a significant role in the development of cartilage defects of the upper ankle joint. Physiotherapeutic procedures belong to the standard procedures of conservative therapy. The use and selection of the type of therapy is based on empirical considerations and experience and investigations on effectiveness of particular therapies are relatively rare. At present a symptom-oriented therapy of cartilage defects of the upper ankle joint seems to be the most sensible approach. It can be assumed that it makes sense that the symptomatic treatment of cartilage defects or initial stages of arthritis also includes the subsequent symptoms of pain, irritated condition and limited function. This leads to starting points for physiotherapy with respect to pain therapy, optimisation of pressure relationships, avoidance of pressure points, improvement of diffusion and pressure release. In addition to the differential physiotherapeutic findings, the determination of a curative, preventive or rehabilitative procedure is especially important. In physical therapy special importance is placed on a scheduled serial application corresponding to the findings, employing the necessary methods, such as physiotherapy, sport therapy, medical mechanics, manual therapy, massage, electrotherapy and warmth therapy. From this the findings-related therapy is proposed as a practical therapy concept: locomotive apparatus pain therapy, optimisation of pressure relationships, improvement of diffusion and decongestion therapy. Therapy options have been selected base on the current literature and are summarised in tabular form. The art of symptomatic therapy of cartilage defects of the upper ankle joint does not lie in the multitude of sometimes speculative procedures, but in the targeted selection of a therapy regime based on the therapeutic goal, a corresponding application dose and serial design.

Good manufacturing practice (GMP) compliance in the biologics sector: plasma fractionation.

PubMed

Ways, J P; Preston, M S; Baker, D; Huxsoll, J; Bablak, J

1999-12-01

The U.S. blood supply is the safest it has ever been. Due to blood safety and the introduction of viral inactivation/clearance technologies, protein therapies derived from human blood have also in recent years had a history of product safety. Nevertheless, since 1995, the plasma-fractionation industry has experienced increased compliance-related actions by the Food and Drug Administration (FDA), as shown by a substantive increase in the number of FDA 483 inspectional observations, FDA warning letters and other FDA regulatory action. An evaluation of these trends shows that they reflect the implementation by the FDA of increased inspectional interest in the plasma-fractionation industry and an evolution of inspectional practices and standards of current good manufacturing practice (cGMP). Plasma fractionators have responded to FDA actions by carefully evaluating and addressing each inspectional observation, assessing impact to product and taking appropriate actions, including corrective actions to prevent future occurrence. They have made major investments in facilities, quality systems, personnel and training to meet the evolving standards of cGMP and in an effort to implement these standards systemically. Through industry associations, manufacturers have further enhanced product safety by adopting additional voluntary standards for plasma to prevent the entry of potentially unsuitable plasma into the production process. The industry remains committed to application of cGMP and to working with the FDA in further evolution of these standards while striving to assure a continued supply of safe, pure and effective plasma-derived therapies.

Manufacture of tumor- and virus-specific T lymphocytes for adoptive cell therapies

PubMed Central

Wang, X; Rivière, I

2015-01-01

Adoptive transfer of tumor-infiltrating lymphocytes (TILs) and genetically engineered T lymphocytes expressing chimeric antigen receptors (CARs) or conventional alpha/beta T-cell receptors (TCRs), collectively termed adoptive cell therapy (ACT), is an emerging novel strategy to treat cancer patients. Application of ACT has been constrained by the ability to isolate and expand functional tumor-reactive T cells. The transition of ACT from a promising experimental regimen to an established standard of care treatment relies largely on the establishment of safe, efficient, robust and cost-effective cell manufacturing protocols. The manufacture of cellular products under current good manufacturing practices (cGMPs) has a critical role in the process. Herein, we review current manufacturing methods for the large-scale production of clinical-grade TILs, virus-specific and genetically modified CAR or TCR transduced T cells in the context of phase I/II clinical trials as well as the regulatory pathway to get these complex personalized cellular products to the clinic. PMID:25721207

Operative colonoscopic endoscopy.

PubMed

Van Gossum, A; Bourgeois, F; Gay, F; Lievens, P; Adler, M; Cremer, M

1992-01-01

There are several conditions where operative colonoscopy is useful. Acute colonic pseudo-obstruction or Ogilvie's syndrome is characterized by a acute distension of the colon. Although medical management may be sufficient in many cases, endoscopic decompression must be performed when colonic distension is greater than 12 cm. Insertion of decompression tube to avoid rapid recurrence seems to be adequate. In case of massive lower intestinal hemorrhage, colonoscopy seems to be more accurate than mesenteric angiography. Such endoscopic examination requires an experienced endoscopist. Colonoscopic polypectomy has become the standard method for removal of colonic polyps. Factors influencing the rate of complications have been studied. While the number of complications was very low, we have observed that all the major hemorrhages were immediate when the blended current was used, but delayed when the pure coagulation current was applied. Endoscopic laser photocavitation is a valuable palliative method treating rectal adenocarcinoma in well selected patients. Indeed, if the patients survive sufficiently long after initial therapy, it becomes increasingly difficult to achieve persistent palliation with laser therapy.

The family assessment device: an update.

PubMed

Mansfield, Abigail K; Keitner, Gabor I; Dealy, Jennifer

2015-03-01

The current study set out to describe family functioning scores of a contemporary community sample, using the Family Assessment Device (FAD), and to compare this to a currently help-seeking sample. The community sample consisted of 151 families who completed the FAD. The help-seeking sample consisted of 46 families who completed the FAD at their first family therapy appointment as part of their standard care at an outpatient family therapy clinic at an urban hospital. Findings suggest that FAD means from the contemporary community sample indicate satisfaction with family functioning, while FAD scores from the help-seeking sample indicate dissatisfaction with family functioning. In addition, the General Functioning scale of the FAD continues to correlate highly with all other FAD scales, except Behavior Control. The cut-off scores for the FAD indicating satisfaction or dissatisfaction by family members with their family functioning continue to be relevant and the FAD continues to be a useful tool to assess family functioning in both clinical and research contexts. © 2014 Family Process Institute.

Manufacture of tumor- and virus-specific T lymphocytes for adoptive cell therapies.

PubMed

Wang, X; Rivière, I

2015-03-01

Adoptive transfer of tumor-infiltrating lymphocytes (TILs) and genetically engineered T lymphocytes expressing chimeric antigen receptors (CARs) or conventional alpha/beta T-cell receptors (TCRs), collectively termed adoptive cell therapy (ACT), is an emerging novel strategy to treat cancer patients. Application of ACT has been constrained by the ability to isolate and expand functional tumor-reactive T cells. The transition of ACT from a promising experimental regimen to an established standard of care treatment relies largely on the establishment of safe, efficient, robust and cost-effective cell manufacturing protocols. The manufacture of cellular products under current good manufacturing practices (cGMPs) has a critical role in the process. Herein, we review current manufacturing methods for the large-scale production of clinical-grade TILs, virus-specific and genetically modified CAR or TCR transduced T cells in the context of phase I/II clinical trials as well as the regulatory pathway to get these complex personalized cellular products to the clinic.

Delivery of large biopharmaceuticals from cardiovascular stents: a review

PubMed Central

Takahashi, Hironobu; Letourneur, Didier; Grainger, David W.

2008-01-01

This review focuses on the new and emerging large-molecule bioactive agents delivered from stent surfaces in drug-eluting stents (DES) to inhibit vascular restenosis in the context of interventional cardiology. New therapeutic agents representing proteins, nucleic acids (small interfering RNAs and large DNA plasmids), viral delivery vectors and even engineered cell therapies require specific delivery designs distinct from traditional smaller molecule approaches on DES. While small molecules are currently the clinical standard for coronary stenting, extension of the DES to other lesion types, peripheral vasculature and non-vasculature therapies will seek to deliver an increasingly sophisticated armada of drug types. This review describes many of the larger molecule and biopharmaceutical approaches reported recently for stent-based delivery with the challenges associated with formulating and delivering these drug classes compared to the current small molecule drugs. It also includes perspectives on possible future applications that may improve safety and efficacy and facilitate diversification of the DES to other clinical applications. PMID:17929968

Protease-activated receptor-1 antagonists in long-term antiplatelet therapy. Current state of evidence and future perspectives.

PubMed

Moschonas, I C; Goudevenos, J A; Tselepis, A D

2015-04-15

Atherothrombosis and its clinical manifestations are among the leading causes of death in the developed world. The current standard-of-care antiplatelet therapy for the treatment of such events comprises aspirin and a thienopyridine or ticagrelor. However, recurrent ischemic events due to residual cardiovascular risk are a common phenomenon in these patients. It is believed that this residual risk is caused, at least in part, by thrombin, which signals through protease-activated receptors (PARs) and especially PAR-1. Thus, PAR-1 antagonism could represent an effective approach in the treatment of atherothrombotic disease. In this context, two potent and selective agents have been developed, vorapaxar and atopaxar. However, only vorapaxar has completed phase 3 clinical trials. In the present review, the main pharmacodynamic and pharmacokinetic properties of the PAR-1 antagonists are briefly described and the latest clinical data on vorapaxar are presented. Copyright © 2015. Published by Elsevier Ireland Ltd.

Stem cell technology for tendon regeneration: current status, challenges, and future research directions

PubMed Central

Lui, Pauline Po Yee

2015-01-01

Tendon injuries are a common cause of physical disability. They present a clinical challenge to orthopedic surgeons because injured tendons respond poorly to current treatments without tissue regeneration and the time required for rehabilitation is long. New treatment options are required. Stem cell-based therapies offer great potential to promote tendon regeneration due to their high proliferative, synthetic, and immunomodulatory activities as well as their potential to differentiate to the target cell types and undergo genetic modification. In this review, I first recapped the challenges of tendon repair by reviewing the anatomy of tendon. Next, I discussed the advantages and limitations of using different types of stem cells compared to terminally differentiated cells for tendon tissue engineering. The safety and efficacy of application of stem cells and their modified counterparts for tendon tissue engineering were then summarized after a systematic literature search in PubMed. The challenges and future research directions to enhance, optimize, and standardize stem cell-based therapies for augmenting tendon repair were then discussed. PMID:26715856

Mirror book therapy for the treatment of idiopathic facial palsy.

PubMed

Barth, Jodi Maron; Stezar, Gincy L; Acierno, Gabriela C; Kim, Thomas J; Reilly, Michael J

2014-09-01

We conducted a retrospective chart review to determine the effectiveness of treating idiopathic facial palsy with mirror book therapy in conjunction with facial physical rehabilitation. We compared outcomes in 15 patients who underwent mirror book therapy in addition to standard therapy with those of 10 patients who underwent standard rehabilitation therapy without the mirror book. Before and after treatment, patients in both groups were rated according to the Facial Grading System (FGS), the Facial Disability Index-Physical (FDIP), and the Facial Disability Index-Social (FDIS). Patients in the mirror therapy group had a mean increase of 24.9 in FGS score, 22.0 in FDIP score, and 25.0 in FDIS score, all of which represented statistically significant improvements over their pretreatment scores. Those who did not receive mirror book therapy had mean increases of 20.8, 19.0, 14.6, respectively; these, too, represented significant improvements over baseline, and thus there was no statistically significant difference in improvement between the two groups. Nevertheless, our results show that patients who used mirror book therapy in addition to standard facial rehabilitation therapy experienced significant improvements in the treatment of idiopathic facial palsy. While further studies are necessary to determine if it has a definitive, statistically significant advantage over standard therapy, we recommend adding this therapy to the rehabilitation program in view of its ease of use, low cost, and lack of side effects.

A fast - Monte Carlo toolkit on GPU for treatment plan dose recalculation in proton therapy

NASA Astrophysics Data System (ADS)

Senzacqua, M.; Schiavi, A.; Patera, V.; Pioli, S.; Battistoni, G.; Ciocca, M.; Mairani, A.; Magro, G.; Molinelli, S.

2017-10-01

In the context of the particle therapy a crucial role is played by Treatment Planning Systems (TPSs), tools aimed to compute and optimize the tratment plan. Nowadays one of the major issues related to the TPS in particle therapy is the large CPU time needed. We developed a software toolkit (FRED) for reducing dose recalculation time by exploiting Graphics Processing Units (GPU) hardware. Thanks to their high parallelization capability, GPUs significantly reduce the computation time, up to factor 100 respect to a standard CPU running software. The transport of proton beams in the patient is accurately described through Monte Carlo methods. Physical processes reproduced are: Multiple Coulomb Scattering, energy straggling and nuclear interactions of protons with the main nuclei composing the biological tissues. FRED toolkit does not rely on the water equivalent translation of tissues, but exploits the Computed Tomography anatomical information by reconstructing and simulating the atomic composition of each crossed tissue. FRED can be used as an efficient tool for dose recalculation, on the day of the treatment. In fact it can provide in about one minute on standard hardware the dose map obtained combining the treatment plan, earlier computed by the TPS, and the current patient anatomic arrangement.

Cytarabine and daunorubicin for the treatment of acute myeloid leukemia.

PubMed

Murphy, Tracy; Yee, Karen W L

2017-11-01

Acute myeloid leukemia (AML) is the most common acute forms of leukemia in adults. It has a poor long-term survival with a high relapse rate and at relapse, is commonly resistant to available therapies. The current combination of daunorubicin (DNR) for three days and cytarabine (Ara-C) as a continuous infusion for seven days, more commonly known as '3 + 7' has remained essentially unaltered over the last forty-four years and remains the standard induction regimen internationally. Areas covered: This paper will briefly review clinically important trials related to '3 + 7'. Somatic mutations in AML that are linked to chemoresistance to '3 + 7'will be discussed. Other topics covered include the novel ratiometric agent containing daunorubicin and cytarabine, CPX-351, and midostaurin in FLT3 mutated AML. Expert opinion: '3 + 7' continues to be the backbone of therapy for AML. However, genetic risk stratification should be used to determine patients who are unlikely to respond to standard intensive chemotherapy and hence, should be enrolled onto a clinical trial upfront. This will facilitate development of newer effective treatment strategies in AML. Patients with mutations that are associated with chemoresistance should be offered therapies which may circumvent or overcome these pathways.

Limitations of the Current Standards of Care for Treating Gout and Crystal Deposition in the Primary Care Setting: A Review.

PubMed

Keenan, Robert T

2017-02-01

This article outlines several important issues regarding the management of patients with gout. The topics discussed include best practices for gout based on the most current guidelines, opportunities for improving gout management, and current and emerging therapies for gout. [PubMed and Google Scholar databases] were search for all articles and trials published before 2016, using the key terms [hyperuricemia, gout, tophi, joint erosion, joint damage, treatment guidelines, American College of Rheumatology (ACR), European League Against Rheumatism (EULAR), flare, comorbidity, epidemiology, adherence, serum uric acid (sUA), monosodium urate (MSU), <6 mg/dL, MSU crystal formation, as well as individual drug names and classes of treatments of interest (allopurinol, febuxostat, colchicine, non-steroidal anti-inflammatories (NSAIDs)]. Studies were selected that presented data on gout treatment, including drugs under development, and on the management of gout from both the physician and patient perspectives. The reference lists of identified articles were searched manually for additional publications. Gout, a progressive debilitating form of inflammatory arthritis, is caused by factors that elevate serum uric acid (sUA) levels, leading to hyperuricemia. Continued elevated sUA can result in monosodium urate crystal deposition in joints and soft tissues, causing acute and chronic inflammation. Crystal deposition can lead to chronic gout, with an increased number of flares, tophi development, and structural joint damage. The aims of gout treatment are to reduce the sUA level to <6 mg/dL, to inhibit the formation of new crystals, and to promote the dissolution of existing crystals. Gout is often poorly managed for several reasons, including a lack of adherence to treatment guidelines by health care providers, patients' poor adherence to therapy, and differences between a provider's and patient's perspectives regarding treatment. Patients need to be educated about their diagnosis and management of the disease, such as the importance of compliance with long-term treatment. Gout treatment may also confounded by contraindications to current standards of therapy and the limitations of current treatment paradigms. Recently approved medications, as well as drugs under development, may provide new ways for reaching the sUA target and also "curing" the disease. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Rapid Intravenous Rehydration Therapy in Children With Acute Gastroenteritis: A Systematic Review.

PubMed

Toaimah, Fatihi Hassan Soliman; Mohammad, Hala Mohammad Fathi

2016-02-01

Rapid intravenous (IV) rehydration is commonly used for the management of pediatric gastroenteritis in the emergency department. The current practice shows wide variation in the volume and rate of rapid IV hydration. The aim of this review was to assess the efficacy of rapid IV rehydration compared with standard method in children with gastroenteritis. MEDLINE (1946-2014), EMBASE (1974-2014), and CENTRAL via the Cochrane Library (Issue 8, 2014) were systematically searched to identify eligible studies. Inclusion criteria were randomized controlled trials of rapid IV rehydration in children with gastroenteritis. A total of 1513 articles were retrieved, and our inclusion criteria were met by 3 studies, with a total of 464 participants. The percentage of children who were successfully rehydrated and tolerated oral fluids at 2 to 4 hours after starting IV fluid therapy ranged from 69% to 100% in both rapid IV rehydration and standard method. Time to discharge ranged from 2 to 6 hours (rapid rehydration) versus 2 to 5 hours (standard rehydration). Emergency department revisits ranged from 3% to 16% (rapid rehydration) versus 5% to 14% (standard). Summarized results suggested that rapid IV rehydration may be associated with longer time-to-discharge and higher readmission rates. The new evidence fails to demonstrate superiority of large-volume (60 mL/kg/h) over standard (20 mL/kg/h) IV rehydration. Standard volume IV rehydration for 1 to 4 hours followed by oral hydration or maintenance IV fluids seems sufficient for most children with gastroenteritis requiring IV fluid administration. However, more evidence is needed to establish an optimal IV rehydration regimen.

Oral rivaroxaban versus standard therapy for the treatment of symptomatic venous thromboembolism: a pooled analysis of the EINSTEIN-DVT and PE randomized studies.

PubMed

Prins, Martin H; Lensing, Anthonie Wa; Bauersachs, Rupert; van Bellen, Bonno; Bounameaux, Henri; Brighton, Timothy A; Cohen, Alexander T; Davidson, Bruce L; Decousus, Hervé; Raskob, Gary E; Berkowitz, Scott D; Wells, Philip S

2013-09-20

Standard treatment for venous thromboembolism (VTE) consists of a heparin combined with vitamin K antagonists. Direct oral anticoagulants have been investigated for acute and extended treatment of symptomatic VTE; their use could avoid parenteral treatment and/or laboratory monitoring of anticoagulant effects. A prespecified pooled analysis of the EINSTEIN-DVT and EINSTEIN-PE studies compared the efficacy and safety of rivaroxaban (15 mg twice-daily for 21 days, followed by 20 mg once-daily) with standard-therapy (enoxaparin 1.0 mg/kg twice-daily and warfarin or acenocoumarol). Patients were treated for 3, 6, or 12 months and followed for suspected recurrent VTE and bleeding. The prespecified noninferiority margin was 1.75. A total of 8282 patients were enrolled; 4151 received rivaroxaban and 4131 received standard-therapy. The primary efficacy outcome occurred in 86 (2.1%) rivaroxaban-treated patients compared with 95 (2.3%) standard-therapy-treated patients (hazard ratio, 0.89; 95% confidence interval [CI], 0.66-1.19; pnoninferiority < 0.001). Major bleeding was observed in 40 (1.0%) and 72 (1.7%) patients in the rivaroxaban and standard-therapy groups, respectively (hazard ratio, 0.54; 95% CI, 0.37-0.79; p = 0.002). In key subgroups, including fragile patients, cancer patients, patients presenting with large clots, and those with a history of recurrent VTE, the efficacy and safety of rivaroxaban were similar compared with standard-therapy. The single-drug approach with rivaroxaban resulted in similar efficacy to standard-therapy and was associated with a significantly lower rate of major bleeding. Efficacy and safety results were consistent among key patient subgroups. ClinicalTrials.gov, NCT00439777; EINSTEIN-DVT: ClinicalTrials.gov, NCT00440193.

New therapeutic options for allergic rhinitis: back to the future with intranasal corticosteroid aerosols.

PubMed

Carr, Warner W

2013-01-01

Under current guidelines, intranasal corticosteroids (INSs) are considered the most effective first-line therapy to improve allergic rhinitis (AR) symptoms and burden of disease. In the late 1980s-1990s, chlorofluorocarbon (CFC)-propelled corticosteroid aerosol nasal sprays formed the standard of care for the treatment of AR. Because of environmental concerns, CFC aerosols were gradually phased out, and aqueous INS formulations of nasal sprays became the standard of care. Although many aqueous INS sprays are available, specific product-related factors can reduce patient adherence to an INS and subsequently reduce treatment efficacy. The purpose of this paper was to review the evolution of AR therapeutics and drug devices and how it may have an effect on patient adherence/compliance and patient satisfaction with current available therapies and show the unmet need to improve INS delivery systems. Although aqueous INSs are effective and well tolerated, use in some patients may be compromised because of patient sensory perception and device preference. A historical review of the evolution of intranasal delivery of INSs was undertaken to provide further insight into improving treatment options for patients with AR. Although the various approved INSs appear to be equivalent in terms of reducing AR disease burden, the method in which an INS is delivered to a patient has significant bearing on the overall success of each specific drug product. Hydrofluoroalkane-propelled INS drug products offer a back-to-the-future delivery approach that may be further tailored to the individual patient's needs. Past experiences and the development of new devices are paving the way toward further therapy choices, ultimately affording health care providers access to the most effective treatments for patients with AR.

Medicare long-term CPAP coverage policy: a cost-utility analysis.

PubMed

Billings, Martha E; Kapur, Vishesh K

2013-10-15

CPAP is an effective treatment for OSA that may reduce health care utilization and costs. Medicare currently reimburses the costs of long-term CPAP therapy only if the patient is adherent during a 90-day trial. If not, Medicare requires a repeat polysomnogram (PSG) and another trial which seems empirically not cost-effective. We modeled the cost-effectiveness of current Medicare policy compared to an alternative policy (clinic-only) without the adherence criterion and repeat PSG. Cost-utility and cost-effectiveness analysis. U.S. Medicare Population. N/A. N/A. We created a decision tree modeling (1) clinic only follow-up vs. (2) current Medicare policy. Costs were assigned based on Medicare reimbursement rates in 2012. Sensitivity analyses were conducted to test our assumptions. We estimated cumulative costs, overall adherence, and QALY gained for a 5-year time horizon from the perspective of Medicare as the payer. Current Medicare policy is more costly than the clinic-only policy but has higher net adherence and improved utility. Current Medicare policy compared to clinic-only policy costs $30,544 more per QALY. Current CMS policy promotes early identification of those more likely to adhere to CPAP therapy by requiring strict adherence standards. The policy effect is to deny coverage to those unlikely to use CPAP long-term and prevent wasted resources. Future studies are needed to measure long-term adherence in an elderly population with and without current adherence requirements to verify the cost-effectiveness of a policy change.

Topical oxygen therapy results in complete wound healing in diabetic foot ulcers.

PubMed

Yu, Janelle; Lu, Suzanne; McLaren, Ann-Marie; Perry, Julie A; Cross, Karen M

2016-11-01

Diabetic foot ulcers (DFUs) are a significant problem in an aging population. Fifteen percent of diabetics develop a DFU over their lifetime, which can lead to potential amputation. The 5-year survival rate after amputation is 31%, which is greater than the lifetime risk of mortality from cancer. Topical oxygen is a promising technique for the adjunctive therapy of chronic wounds including DFUs, but few controlled studies exist to support its clinical adoption. The aim of this study was to compare a portable topical oxygen delivery system in patients with nonhealing DFUs to standard best practice. Twenty patients were randomized into a topical oxygen group (n = 10), and a nonplacebo control group with regular dressings and standard care (n = 10), and attended the diabetic foot clinic once weekly for 8 weeks. Ulcer surface area over time was analyzed using standardized digital imaging software. DFUs were present without healing for a mean duration of 76 weeks prior to the study. They found a significant difference in healing rate between patients receiving topical oxygen and those receiving standard care. Topical oxygen, therefore, represents a potentially exciting new technology to shorten healing time in patients with nonhealing DFUs. More prospective randomized and powered studies are needed to determine the benefits of topical oxygen, but our current results are very promising. © 2016 by the Wound Healing Society.

Development of the First World Health Organization Lentiviral Vector Standard: Toward the Production Control and Standardization of Lentivirus-Based Gene Therapy Products

PubMed Central

Zhao, Yuan; Stepto, Hannah; Schneider, Christian K

2017-01-01

Gene therapy is a rapidly evolving field. So far, there have been >2,400 gene therapy products in clinical trials and four products on the market. A prerequisite for producing gene therapy products is ensuring their quality and safety. This requires appropriately controlled and standardized production and testing procedures that result in consistent safety and efficacy. Assuring the quality and safety of lentivirus-based gene therapy products in particular presents a great challenge because they are cell-based multigene products that include viral and therapeutic proteins as well as modified cells. In addition to the continuous refinement of a product, changes in production sites and manufacturing processes have become more and more common, posing challenges to developers regarding reproducibility and comparability of results. This paper discusses the concept of developing a first World Health Organization International Standard, suitable for the standardization of assays and enabling comparison of cross-trial and cross-manufacturing results for this important vector platform. The standard will be expected to optimize the development of gene therapy medicinal products, which is especially important, given the usually orphan nature of the diseases to be treated, naturally hampering reproducibility and comparability of results. PMID:28747142

Current advances in T-cell-based cancer immunotherapy

PubMed Central

Wang, Mingjun; Yin, Bingnan; Wang, Helen Y; Wang, Rong-Fu

2015-01-01

Cancer is a leading cause of death worldwide; due to the lack of ideal cancer biomarkers for early detection or diagnosis, most patients present with late-stage disease at the time of diagnosis, thus limiting the potential for successful treatment. Traditional cancer treatments, including surgery, chemotherapy and radiation therapy, have demonstrated very limited efficacy for patients with late-stage disease. Therefore, innovative and effective cancer treatments are urgently needed for cancer patients with late-stage and refractory disease. Cancer immunotherapy, particularly adoptive cell transfer, has shown great promise in the treatment of patients with late-stage disease, including those who are refractory to standard therapies. In this review, we will highlight recent advances and discuss future directions in adoptive cell transfer based cancer immunotherapy. PMID:25524383

Current status and future therapeutic perspectives of glioblastoma multiforme (GBM) therapy: A review.

PubMed

Anjum, Komal; Shagufta, Bibi Ibtesam; Abbas, Syed Qamar; Patel, Seema; Khan, Ishrat; Shah, Sayed Asmat Ali; Akhter, Najeeb; Hassan, Syed Shams Ul

2017-08-01

Glioblastoma multiforme (GBM) is the deadliest form of heterogeneous brain cancer. It affects an enormous number of patients every year and the survival is approximately 8 to 15 months. GBM has driven by complex signaling pathways and considered as a most challenging to treat. Standard treatment of GBM includes surgery, radiation therapy, chemotherapy and also the combined treatment. This review article described inter and intra- tumor heterogeneity of GMB. In addition, recent chemotherapeutic agents, with their mechanism of action have been defined. FDA-approved drugs also been focused over here and most importantly highlighting some natural and synthetic and novel anti- glioma agents, that are the main focus of researchers nowadays. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Minimally invasive treatment for localized prostate cancer.

PubMed

Porres, D; Pfister, D; Heidenreich, A

2012-12-01

The vast majority of men newly diagnosed with prostate cancer have clinically localized disease. Besides active surveillance in low risk cancers and open radical prostatectomy as the traditional gold standard more and more patients demand a effective tumor control through a minimally invasive approach. After the introduction of laparoscopy for the treatment of prostate cancer especially the robot-assisted radical prostatectomy gained in importance. In recent years the accuracy for cancer localisation within the prostate was considerably improved, which enables the increasing use of focal therapy techniques. In addition to the robot-assisted and conventional laparoscopic radical prostatectomy the current and future importance of cryotherapy, HIFU and vascular targeted photodynamic therapy for localized prostate cancer will be analyzed in the following review article.

Microbial Biofilms and Chronic Wounds

PubMed Central

Omar, Amin; Wright, J. Barry; Schultz, Gregory; Burrell, Robert; Nadworny, Patricia

2017-01-01

Background is provided on biofilms, including their formation, tolerance mechanisms, structure, and morphology within the context of chronic wounds. The features of biofilms in chronic wounds are discussed in detail, as is the impact of biofilm on wound chronicity. Difficulties associated with the use of standard susceptibility tests (minimum inhibitory concentrations or MICs) to determine appropriate treatment regimens for, or develop new treatments for use in, chronic wounds are discussed, with alternate test methods specific to biofilms being recommended. Animal models appropriate for evaluating biofilm treatments are also described. Current and potential future therapies for treatment of biofilm-containing chronic wounds, including probiotic therapy, virulence attenuation, biofilm phenotype expression attenuation, immune response suppression, and aggressive debridement combined with antimicrobial dressings, are described. PMID:28272369

Treatment-resistant depressed patients show a good response to Mindfulness-based Cognitive Therapy

PubMed Central

Kenny, M.A.; Williams, J.M.G.

2007-01-01

Mindfulness-based Cognitive Therapy (MBCT) is a class-based programme designed for use in the prevention of relapse of major depression. Its aim is to teach participants to disengage from those cognitive processes that may render them vulnerable to future episodes. These same cognitive processes are also known to maintain depression once established, hence a clinical audit was conducted to explore the use of MBCT in patients who were currently actively depressed, and who had not responded fully to standard treatments. The study showed that it was acceptable to these patients and resulted in an improvement in depression scores (pre-post Effect Size=1.04), with a significant proportion of patients returning to normal or near-normal levels of mood. PMID:16797486

Current advances in T-cell-based cancer immunotherapy.

PubMed

Wang, Mingjun; Yin, Bingnan; Wang, Helen Y; Wang, Rong-Fu

2014-01-01

Cancer is a leading cause of death worldwide; due to the lack of ideal cancer biomarkers for early detection or diagnosis, most patients present with late-stage disease at the time of diagnosis, thus limiting the potential for successful treatment. Traditional cancer treatments, including surgery, chemotherapy and radiation therapy, have demonstrated very limited efficacy for patients with late-stage disease. Therefore, innovative and effective cancer treatments are urgently needed for cancer patients with late-stage and refractory disease. Cancer immunotherapy, particularly adoptive cell transfer, has shown great promise in the treatment of patients with late-stage disease, including those who are refractory to standard therapies. In this review, we will highlight recent advances and discuss future directions in adoptive cell transfer based cancer immunotherapy.

Historical aspects of Pott's disease (spinal tuberculosis) management.

PubMed

Tuli, Surendar M

2013-06-01

Spinal tuberculosis has existed in human beings since the ascent of man on earth. Historically, the management has progressed from regional orthodox therapies to the current, more effective, drugs. Historical perspectives regarding the management have been collated by going through the important publications during the past 6 decades. For convenience, the manuscript has been organized as "orthodox traditional" treatment, early "chemotherapy period", "post chemotherapy treatment", "middle-path" philosophy, and the current treatment with availability of modern imaging facilities. Broad conclusions based upon the published data and personal observations (1959-2011) are summarized as follows: If diagnosis is made at predestructive stage and the patient is treated by standard drugs, the infection would heal in about 95 % patients without significant deformities and complications. Neural complications are still encountered in general hospital outpatients. Diagnosis and treatment at early stages would resolve the neurology without operation in about 40 % of cases. Nearly 60 % of patients would require to be operatively decompressed without jeopardizing mechanical stability. However, despite current treatment approximately 8 % of tuberculous paraplegics do not recover functionally. Immunocompromised state and multidrug resistance to standard drugs (8 to 10 %) are the current (and future) challenges to the doctors and the society.

The course of the working alliance during virtual reality and exposure group therapy for social anxiety disorder.

PubMed

Ngai, Irene; Tully, Erin C; Anderson, Page L

2015-03-01

Psychoanalytic theory and some empirical research suggest the working alliance follows a "rupture and repair" pattern over the course of therapy, but given its emphasis on collaboration, cognitive behavioral therapy may yield a different trajectory. The current study compares the trajectory of the working alliance during two types of cognitive behavioral therapy for social anxiety disorder - virtual reality exposure therapy (VRE) and exposure group therapy (EGT), one of which (VRE) has been proposed to show lower levels of working alliance due to the physical barriers posed by the technology (e.g. no eye contact with therapist during exposure). Following randomization, participants (N = 63) diagnosed with social anxiety disorder received eight sessions of manualized EGT or individual VRE and completed a standardized self-report measure of working alliance after each session. Hierarchical linear modeling showed overall high levels of working alliance that changed in rates of growth over time; that is, increases in working alliance scores were steeper at the beginning of therapy and slowed towards the end of therapy. There were no differences in working alliance between the two treatment groups. Results neither support a rupture/repair pattern nor the idea that the working alliance is lower for VRE participants. Findings are consistent with the idea that different therapeutic approaches may yield different working alliance trajectories.

Cystic Echinococcal Liver Disease: New Insights into an Old Disease and an Algorithm for Therapy Planning

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

Rozanes, Izzet, E-mail: rozanes@superonline.com; Gueven, Koray; Acunas, Buelent

2007-11-15

Human cystic echinococcosis (CE) continues to be a major health problem in developing countries. A review of current literature discloses four alternatives for the management of active CE, consisting of surgery, percutaneous treatment (PT), chemotherapy, and follow-up without intervention, but no clear guidelines for directing patients to the different management options. Palliation of symptoms or prevention of complications is the main rationale for the treatment of CE. Surgery has long been considered as the gold standard treatment. However, a meta-analysis comparing the clinical outcomes of patients treated with PT with those of a control group treated with surgery found PTmore » to be more effective, safer, and cheaper. Medical therapy is considered to be ineffective when the criterion of success is defined as the disappearance of the lesion. However, medical therapy seems to be effective when the goal of therapy is defined as the prevention of complications in asymptomatic patients. We propose an algorithm for therapy planning in CE where the first line of therapy for patients with active lesions is PT. Patients with lesions unsuitable for PT are directed to surgery if they are symptomatic, have complicated lesions or have lesions that are prone to rupture. Asymptomatic patients with uncomplicated lesions are directed to medical therapy. Medical therapy failures are redirected to surgery.« less

[A case of lung metastasis from esophageal cancer resistant to fluorouracil and cisplatin combination therapy but responsive to radiation therapy].

PubMed

Ami, Katsunori; Seki, Ryouta; Takasaki, Jun; Amagasa, Hidetoshi; Kamikozuru, Hirotaka; Ganno, Hideaki; Kurokawa, Toshiaki; Fukuda, Akira; Nagahama, Takeshi; Ando, Masayuki; Yamada, Yosuke; Kodaka, Fumi; Arai, Kuniyoshi

2012-11-01

At present, fluorouracil and cisplatin combination therapy is the standard chemotherapy against esophageal cancer, but the choice of second-line chemotherapy is controversial. Furthermore, the effect of radiation therapy against lung metastasis from esophageal cancer is unclear. We report a case of lung metastasis from esophageal cancer resistant to fluorouracil and cisplatin combination therapy but responsive to radiation therapy. The patient was a 55-year-old woman who had undergone an operation for esophageal cancer at another hospital. A single right lung metastasis appeared 1 year after the operation. Combined fluorouracil and cisplatin therapy was administrated for 5 courses, but the lung metastasis increased in size. Afterwards, she was admitted to our hospital. We treated her with 14 courses of S-1 and docetaxel combination therapy administered over 13 months. The lung metastasis was decreased for a period. Furthermore, radiofrequency ablation under computed tomography was performed against the lung metastasis re-growth at another hospital. Although the lung metastasis increased in size, no further metastases were detected during the clinical course. The patient was treated with radiotherapy for the lung metastasis re-growth. The tumor had almost disappeared by 10 months after the completion of radiotherapy. Currently, she is receiving palliative care as an outpatient and the lung metastasis has not been evident for 2 years since the completion of radiotherapy.

Investigation of standard care versus sham Reiki placebo versus actual Reiki therapy to enhance comfort and well-being in a chemotherapy infusion center.

PubMed

Catlin, Anita; Taylor-Ford, Rebecca L

2011-05-01

To determine whether provision of Reiki therapy during outpatient chemotherapy is associated with increased comfort and well-being. Double-blind, randomized clinical controlled trial. Outpatient chemotherapy center. 189 participants were randomized to actual Reiki, sham Reiki placebo, or standard care. Patients receiving chemotherapy were randomly placed into one of three groups. Patients received either standard care, a placebo, or an actual Reiki therapy treatment. A demographic tool and pre- and post-tests were given before and after chemotherapy infusion. Reiki therapy, sham Reiki placebo therapy, standard care, and self-reported levels of comfort and well-being pre- and postintervention. Although Reiki therapy was statistically significant in raising the comfort and well-being of patients post-therapy, the sham Reiki placebo also was statistically significant. Patients in the standard care group did not experience changes in comfort and well-being during their infusion session. The findings indicate that the presence of an RN providing one-on-one support during chemotherapy was influential in raising comfort and well-being levels, with or without an attempted healing energy field. An attempt by clinic nurses to provide more designated one-to-one presence and support for patients while receiving their chemotherapy infusions could increase patient comfort and well-being.

Autophagosomal Sequestration of Mitochondria as an Indicator of Antiandrogen Therapy Resistance of Prostate Cancer (PCa)

DTIC Science & Technology

2017-11-01

this report are those of the author(s) and should not be construed as an official Department of the Army position, policy or decision unless so...dependent LNCaP and –independent C4-2 cells are studied first. Autophagy is monitored by cellular fluorescence in cells treated with...sensitive LNCaP cells. Mitophagy in circulating tumor cells (CTCs) isolated from patient blood samples are currently being standardized. 15. SUBJECT TERMS

National Intrepid Center of Excellence: Cutting Edge Interdisciplinary Care for TBI & PH

DTIC Science & Technology

2011-01-26

training • Autogenic Training : Heart Math • Pain Control: Acupuncture, Relaxation • Family Therapy: FOCUS • Wellness: Yoga, Nutrition, Rec, Art... training venue for the dissemination of next generation standards of care and resilience to providers as well as Service Members and families  An...on the NICoE Website (Currently under development) 8 • NICoE’s Training and Education (T&E) mission is to serve as: – An education catalyst for

HIV antiretroviral medication stock-outs in Ghana: contributors and consequences.

PubMed

Poku, Rebecca A; Owusu, Adobea Yaa; Mullen, Patricia Dolan; Markham, Christine; McCurdy, Sheryl A

2017-09-01

Drug stock-outs are an unfortunate yet common reality for patients living in low and middle income countries, particularly in sub-Saharan Africa where trouble with consistent stock of antiretroviral medications (ARVs) continues. Our study takes a snapshot of this problem in Ghana. Although the country launched its antiretroviral therapy (ART) programme in 2003, progress toward realising the full benefit of ART for treated individuals has been limited, in part, because of stock-outs. In Ghana's Greater Accra region, we conducted semi-structured interviews with 40 women living with HIV (WLHIV) and 15 individuals with a history of HIV-related work in government or non-governmental organisations, or healthcare facilities. We used repeated review with coding and mapping techniques to analyse the transcripts and identify common themes. Stock-outs of ARVs result in inconsistent administration of therapy, increased indirect medical costs for WLHIV, and negative labelling of patients. Inefficiencies in drug supply, poor coordination with port authorities, inadequate government funding and dependence on international aid contribute to the stock-outs experienced in Ghana. Although using ARVs produced in-country could reduce supply problems, the domestically-manufactured product currently does not meet World Health Organization (WHO) standards. We recommend focused efforts to produce WHO standard ARVs in Ghana, and a review of current supply chain management to identify and mend pitfalls in the system.

Small animal radiotherapy research platforms

NASA Astrophysics Data System (ADS)

Verhaegen, Frank; Granton, Patrick; Tryggestad, Erik

2011-06-01

Advances in conformal radiation therapy and advancements in pre-clinical radiotherapy research have recently stimulated the development of precise micro-irradiators for small animals such as mice and rats. These devices are often kilovolt x-ray radiation sources combined with high-resolution CT imaging equipment for image guidance, as the latter allows precise and accurate beam positioning. This is similar to modern human radiotherapy practice. These devices are considered a major step forward compared to the current standard of animal experimentation in cancer radiobiology research. The availability of this novel equipment enables a wide variety of pre-clinical experiments on the synergy of radiation with other therapies, complex radiation schemes, sub-target boost studies, hypofractionated radiotherapy, contrast-enhanced radiotherapy and studies of relative biological effectiveness, to name just a few examples. In this review we discuss the required irradiation and imaging capabilities of small animal radiation research platforms. We describe the need for improved small animal radiotherapy research and highlight pioneering efforts, some of which led recently to commercially available prototypes. From this, it will be clear that much further development is still needed, on both the irradiation side and imaging side. We discuss at length the need for improved treatment planning tools for small animal platforms, and the current lack of a standard therein. Finally, we mention some recent experimental work using the early animal radiation research platforms, and the potential they offer for advancing radiobiology research.

Intensified treatment with high dose Rifampicin and Levofloxacin compared to standard treatment for adult patients with Tuberculous Meningitis (TBM-IT): protocol for a randomized controlled trial

PubMed Central

2011-01-01

Background Tuberculous meningitis is the most severe form of tuberculosis. Mortality for untreated tuberculous meningitis is 100%. Despite the introduction of antibiotic treatment for tuberculosis the mortality rate for tuberculous meningitis remains high; approximately 25% for HIV-negative and 67% for HIV positive patients with most deaths occurring within one month of starting therapy. The high mortality rate in tuberculous meningitis reflects the severity of the condition but also the poor antibacterial activity of current treatment regimes and relatively poor penetration of these drugs into the central nervous system. Improving the antitubercular activity in the central nervous system of current therapy may help improve outcomes. Increasing the dose of rifampicin, a key drug with known poor cerebrospinal fluid penetration may lead to higher drug levels at the site of infection and may improve survival. Of the second generation fluoroquinolones, levofloxacin may have the optimal pharmacological features including cerebrospinal fluid penetration, with a ratio of Area Under the Curve (AUC) in cerebrospinal fluid to AUC in plasma of >75% and strong bactericidal activity against Mycobacterium tuberculosis. We propose a randomized controlled trial to assess the efficacy of an intensified anti-tubercular treatment regimen in tuberculous meningitis patients, comparing current standard tuberculous meningitis treatment regimens with standard treatment intensified with high-dose rifampicin and additional levofloxacin. Methods/Design A randomized, double blind, placebo-controlled trial with two parallel arms, comparing standard Vietnamese national guideline treatment for tuberculous meningitis with standard treatment plus an increased dose of rifampicin (to 15 mg/kg/day total) and additional levofloxacin. The study will include 750 patients (375 per treatment group) including a minimum of 350 HIV-positive patients. The calculation assumes an overall mortality of 40% vs. 30% in the two arms, respectively (corresponding to a target hazard ratio of 0.7), a power of 80% and a two-sided significance level of 5%. Randomization ratio is 1:1. The primary endpoint is overall survival, i.e. time from randomization to death during a follow-up period of 9 months. Secondary endpoints are: neurological disability at 9 months, time to new neurological event or death, time to new or recurrent AIDS-defining illness or death (in HIV-positive patients only), severe adverse events, and rate of treatment interruption for adverse events. Discussion Currently very few options are available for the treatment of TBM and the mortality rate remains unacceptably high with severe disabilities seen in many of the survivors. This trial is based on the hypothesis that current anti-mycobacterial treatment schedules for TBM are not potent enough and that outcomes will be improved by increasing the CSF penetrating power of this regimen by optimising dosage and using additional drugs with better CSF penetration. Trial registration International Standard Randomised Controlled Trial Number ISRCTN61649292 PMID:21288325

Intensified treatment with high dose rifampicin and levofloxacin compared to standard treatment for adult patients with tuberculous meningitis (TBM-IT): protocol for a randomized controlled trial.

PubMed

Heemskerk, Dorothee; Day, Jeremy; Chau, Tran Thi Hong; Dung, Nguyen Huy; Yen, Nguyen Thi Bich; Bang, Nguyen Duc; Merson, Laura; Olliaro, Piero; Pouplin, Thomas; Caws, Maxine; Wolbers, Marcel; Farrar, Jeremy

2011-02-02

Tuberculous meningitis is the most severe form of tuberculosis. Mortality for untreated tuberculous meningitis is 100%. Despite the introduction of antibiotic treatment for tuberculosis the mortality rate for tuberculous meningitis remains high; approximately 25% for HIV-negative and 67% for HIV positive patients with most deaths occurring within one month of starting therapy. The high mortality rate in tuberculous meningitis reflects the severity of the condition but also the poor antibacterial activity of current treatment regimes and relatively poor penetration of these drugs into the central nervous system. Improving the antitubercular activity in the central nervous system of current therapy may help improve outcomes. Increasing the dose of rifampicin, a key drug with known poor cerebrospinal fluid penetration may lead to higher drug levels at the site of infection and may improve survival. Of the second generation fluoroquinolones, levofloxacin may have the optimal pharmacological features including cerebrospinal fluid penetration, with a ratio of Area Under the Curve (AUC) in cerebrospinal fluid to AUC in plasma of >75% and strong bactericidal activity against Mycobacterium tuberculosis. We propose a randomized controlled trial to assess the efficacy of an intensified anti-tubercular treatment regimen in tuberculous meningitis patients, comparing current standard tuberculous meningitis treatment regimens with standard treatment intensified with high-dose rifampicin and additional levofloxacin. A randomized, double blind, placebo-controlled trial with two parallel arms, comparing standard Vietnamese national guideline treatment for tuberculous meningitis with standard treatment plus an increased dose of rifampicin (to 15 mg/kg/day total) and additional levofloxacin. The study will include 750 patients (375 per treatment group) including a minimum of 350 HIV-positive patients. The calculation assumes an overall mortality of 40% vs. 30% in the two arms, respectively (corresponding to a target hazard ratio of 0.7), a power of 80% and a two-sided significance level of 5%. Randomization ratio is 1:1. The primary endpoint is overall survival, i.e. time from randomization to death during a follow-up period of 9 months. Secondary endpoints are: neurological disability at 9 months, time to new neurological event or death, time to new or recurrent AIDS-defining illness or death (in HIV-positive patients only), severe adverse events, and rate of treatment interruption for adverse events. Currently very few options are available for the treatment of TBM and the mortality rate remains unacceptably high with severe disabilities seen in many of the survivors. This trial is based on the hypothesis that current anti-mycobacterial treatment schedules for TBM are not potent enough and that outcomes will be improved by increasing the CSF penetrating power of this regimen by optimising dosage and using additional drugs with better CSF penetration. International Standard Randomised Controlled Trial Number ISRCTN61649292.

Bezlotoxumab: anti-toxin B monoclonal antibody to prevent recurrence of Clostridium difficile infection.

PubMed

Villafuerte Gálvez, Javier A; Kelly, Ciarán P

2017-07-01

Clostridium difficile infection (CDI) is the most common nosocomial infection in the U.S. 25% of CDI patients go on to develop recurrent CDI (rCDI) following current standard of care (SOC) therapy, leading to morbidity, mortality and economic loss. The first passive immunotherapy drug targeting C.difficile toxin B (bezlotoxumab) has been approved recently by the FDA and EMA for prevention of rCDI. Areas covered: A body of key studies was selected and reviewed by the authors. The unmet needs in CDI care were ascertained with emphasis in rCDI, including the epidemiology, pathophysiology and current management. The current knowledge about the immune response to C. difficile toxins and how this knowledge led to the development and the clinical use of bezlotoxumab is described. Current and potential future competitors to the drug were examined. Expert commentary: A single 10 mg/kg intravenous infusion of bezlotoxumab has been shown to decrease rCDI by ~40% (absolute reduction ~10%) in patients being treated for primary CDI or rCDI with SOC antibiotics. Targeting C.difficile toxins by passive immunotherapy is a novel mechanism for prevention of C.difficile infection. Bezlotoxumab will be a valuable adjunctive therapy to reduce the burden of CDI.

When the value of gold is zero.

PubMed

Chase, J Geoffrey; Moeller, Knut; Shaw, Geoffrey M; Schranz, Christoph; Chiew, Yeong Shiong; Desaive, Thomas

2014-06-27

This manuscript presents the concerns around the increasingly common problem of not having readily available or useful "gold standard" measurements. This issue is particularly important in critical care where many measurements used in decision making are surrogates of what we would truly wish to use. However, the question is broad, important and applicable in many other areas.In particular, a gold standard measurement often exists, but is not clinically (or ethically in some cases) feasible. The question is how does one even begin to develop new measurements or surrogates if one has no gold standard to compare with?We raise this issue concisely with a specific example from mechanical ventilation, a core bread and butter therapy in critical care that is also a leading cause of length of stay and cost of care. Our proposed solution centers around a hierarchical validation approach that we believe would ameliorate ethics issues around radiation exposure that make current gold standard measures clinically infeasible, and thus provide a pathway to create a (new) gold standard.

Strict glycaemic control in patients hospitalised in a mixed medical and surgical intensive care unit: a randomised clinical trial

PubMed Central

De La Rosa, Gisela Del Carmen; Donado, Jorge Hernando; Restrepo, Alvaro Humberto; Quintero, Alvaro Mauricio; González, Luis Gabriel; Saldarriaga, Nora Elena; Bedoya, Marisol; Toro, Juan Manuel; Velásquez, Jorge Byron; Valencia, Juan Carlos; Arango, Clara Maria; Aleman, Pablo Henrique; Vasquez, Esdras Martin; Chavarriaga, Juan Carlos; Yepes, Andrés; Pulido, William; Cadavid, Carlos Alberto

2008-01-01

Introduction Critically ill patients can develop hyperglycaemia even if they do not have diabetes. Intensive insulin therapy decreases morbidity and mortality rates in patients in a surgical intensive care unit (ICU) and decreases morbidity in patients in a medical ICU. The effect of this therapy on patients in a mixed medical/surgical ICU is unknown. Our goal was to assess whether the effect of intensive insulin therapy, compared with standard therapy, decreases morbidity and mortality in patients hospitalised in a mixed ICU. Methods This is a prospective, randomised, non-blinded, single-centre clinical trial in a medical/surgical ICU. Patients were randomly assigned to receive either intensive insulin therapy to maintain glucose levels between 80 and 110 mg/dl (4.4 to 6.1 mmol/l) or standard insulin therapy to maintain glucose levels between 180 and 200 mg/dl (10 and 11.1 mmol/l). The primary end point was mortality at 28 days. Results Over a period of 30 months, 504 patients were enrolled. The 28-day mortality rate was 32.4% (81 of 250) in the standard insulin therapy group and 36.6% (93 of 254) in the intensive insulin therapy group (Relative Risk [RR]: 1.1; 95% confidence interval [CI]: 0.85 to 1.42). The ICU mortality in the standard insulin therapy group was 31.2% (78 of 250) and 33.1% (84 of 254) in the intensive insulin therapy group (RR: 1.06; 95%CI: 0.82 to 1.36). There was no statistically significant reduction in the rate of ICU-acquired infections: 33.2% in the standard insulin therapy group compared with 27.17% in the intensive insulin therapy group (RR: 0.82; 95%CI: 0.63 to 1.07). The rate of hypoglycaemia (≤ 40 mg/dl) was 1.7% in the standard insulin therapy group and 8.5% in the intensive insulin therapy group (RR: 5.04; 95% CI: 1.20 to 21.12). Conclusions IIT used to maintain glucose levels within normal limits did not reduce morbidity or mortality of patients admitted to a mixed medical/surgical ICU. Furthermore, this therapy increased the risk of hypoglycaemia. Trial Registration clinicaltrials.gov Identifiers: 4374-04-13031; 094-2 in 000966421 PMID:18799004

Vascular endothelial growth factor inhibitor use and treatment approach for choroidal neovascularization secondary to pathologic myopia.

PubMed

Pakzad-Vaezi, Kaivon; Mehta, Hemal; Mammo, Zaid; Tufail, Adnan

2016-07-01

Myopic choroidal neovascularization (CNV) is the most common cause of CNV in those under 50 years of age. It is a significant cause of visual loss in those with pathologic myopia. The current standard of care involves therapy with intravitreal inhibitors of vascular endothelial growth factor (VEGF). The epidemiology of myopia, high myopia, pathologic myopia, and myopic CNV is reviewed, along with a brief discussion of historical treatments. The pharmacology of the three most commonly used anti-VEGF agents is discussed, with an emphasis on the licensed drugs, ranibizumab and aflibercept. A comprehensive clinical approach to diagnosis and treatment of myopic CNV is presented. The current standard of care for myopic CNV is intravitreal inhibition of VEGF, with ranibizumab and aflibercept licensed for intraocular use. The diagnosis, OCT features of disease activity and retreatment algorithm for myopic CNV is different from wet age-related macular degeneration. In the long-term, myopic CNV may be associated with gradual, irreversible visual loss due to progressive chorioretinal atrophy, for which there is currently no treatment.

Music therapy for depression.

PubMed

Maratos, A S; Gold, C; Wang, X; Crawford, M J

2008-01-23

Depression is a highly prevalent disorder associated with reduced social functioning, impaired quality of life, and increased mortality. Music therapy has been used in the treatment of a variety of mental disorders, but its impact on those with depression is unclear. To examine the efficacy of music therapy with standard care compared to standard care alone among people with depression and to compare the effects of music therapy for people with depression against other psychological or pharmacological therapies. CCDANCTR-Studies and CCDANCTR-References were searched on 7/11/2007, MEDLINE, PsycINFO, EMBASE, PsycLit, PSYindex, and other relevant sites were searched in November 2006. Reference lists of retrieved articles were hand searched, as well as specialist music and arts therapies journals. All randomised controlled trials comparing music therapy with standard care or other interventions for depression. Data on participants, interventions and outcomes were extracted and entered onto a database independently by two review authors. The methodological quality of each study was also assessed independently by two review authors. The primary outcome was reduction in symptoms of depression, based on a continuous scale. Five studies met the inclusion criteria of the review. Marked variations in the interventions offered and the populations studied meant that meta-analysis was not appropriate. Four of the five studies individually reported greater reduction in symptoms of depression among those randomised to music therapy than to those in standard care conditions. The fifth study, in which music therapy was used as an active control treatment, reported no significant change in mental state for music therapy compared with standard care. Dropout rates from music therapy conditions appeared to be low in all studies. Findings from individual randomised trials suggest that music therapy is accepted by people with depression and is associated with improvements in mood. However, the small number and low methodological quality of studies mean that it is not possible to be confident about its effectiveness. High quality trials evaluating the effects of music therapy on depression are required.

SERA -- An advanced treatment planning system for neutron therapy and BNCT

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

Nigg, D.W.; Wemple, C.A.; Wessol, D.E.

1999-09-01

Detailed treatment planning calculations on a patient-specific basis are required for boron neutron capture therapy (BNCT). Two integrated treatment planning systems developed specifically for BNCT have been in clinical use in the United States over the past few years. The MacNCTPLAN BNCT treatment planning system is used in the clinical BNCT trials that are underway at the Massachusetts Institute of Technology. A second system, BNCT{_}rtpe (BNCT radiation therapy planning environment), developed independently by the Idaho national Engineering and Environmental Laboratory (INEEL) in collaboration with Montana State University (MSU), is used for treatment planning in the current series of BNCT clinicalmore » trials for glioblastoma at Brookhaven National Laboratory (BNL). This latter system is also licensed for use at several other BNCT research facilities worldwide. Although the currently available BNCT planning systems have served their purpose well, they suffer from somewhat long computation times (2 to 3 CPU-hours or more per field) relative to standard photon therapy planning software. This is largely due to the need for explicit three-dimensional solutions to the relevant transport equations. The simplifying approximations that work well for photon transport computations are not generally applicable to neutron transport computations. Greater computational speeds for BNCT treatment planning must therefore generally be achieved through the application of improved numerical techniques rather than by simplification of the governing equations. Recent efforts at INEEL and MSU have been directed toward this goal. This has resulted in a new paradigm for this type of calculation and the subsequent creation of the new simulation environment for radiotherapy applications (SERA) treatment planning system for BNCT. SERA is currently in initial clinical testing in connection with the trials at BNL, and it is expected to replace the present BNCT{_}rtpe system upon general release during 1999.« less

[Cost of an intraperitoneal chemohyperthermia (IPCH) related to cytoreductive surgery].

PubMed

Bonastre, J; Jan, P; de Pouvourville, G; Pocard, M; Estphan, G; Elias, D

2005-10-01

A complete cytoreductive surgery followed with an intraperitoneal chemohyperthermia (IPCH) is a new treatment allowing curing some patients with a peritoneal carcinomatosis. The cost of this treatment, evaluated in different countries, is high. In France, we do not have any cost evaluation of this therapy, and this state slows its diffusion in our country. The aim of this study is to evaluate the real cost of maximal cytoreductive surgery with IPCH, and to compare it with the financial support given by the Ministery of Health. The real cost of this therapy was established on the standard analytic accountancy of our Institute. The analysis of the financial support received was done after the classification of the patients in the current official diagnosis-related groups, and according to the current rates of reimbursing of these acts. Seventy-three patients were treated with IPCH in our Institute during 2002 and 2003. The real mean cost for our hospital was 39,358 euros per patient, with a mean hospital staying of 27.7 days. In counterpart, our hospital received a mean financial support of 20,485 euros, resulting in a deficit of 18,873 euros per patient (and close to 1.4 million of euros for the two years). Our current classification of diagnosis-related groups does not allow to describe the real importance of this therapy which combines a maximal cytoreductive surgery with IPCH. In our system of reimbursing, the hospital which offers this type of new therapy to its patients receives only half of the real rate. Two correctives measures are suitable: to describe this combining treatment in the official list of medical acts, and to determine its specific cost for reimbursing.

A Randomised Trial of empiric 14-day Triple, five-day Concomitant, and ten-day Sequential Therapies for Helicobacter pylori in Seven Latin American Sites

PubMed Central

Greenberg, E. Robert; Anderson, Garnet L.; Morgan, Douglas R.; Torres, Javier; Chey, William D.; Bravo, Luis Eduardo; Dominguez, Ricardo L.; Ferreccio, Catterina; Herrero, Rolando; Lazcano-Ponce, Eduardo C.; Meza-Montenegro, Mercedes María; Peña, Rodolfo; Peña, Edgar M.; Salazar-Martínez, Eduardo; Correa, Pelayo; Martínez, María Elena; Valdivieso, Manuel; Goodman, Gary E.; Crowley, John J.; Baker, Laurence H.

2011-01-01

Summary Background Evidence from Europe, Asia, and North America suggests that standard three-drug regimens of a proton pump inhibitor plus amoxicillin and clarithromycin are significantly less effective for eradicating Helicobacter pylori (H. pylori) infection than five-day concomitant and ten-day sequential four-drug regimens that include a nitroimidazole. These four-drug regimens also entail fewer antibiotic doses and thus may be suitable for eradication programs in low-resource settings. Studies are limited from Latin America, however, where the burden of H. pylori-associated diseases is high. Methods We randomised 1463 men and women ages 21–65 selected from general populations in Chile, Colombia, Costa Rica, Honduras, Nicaragua, and Mexico (two sites) who tested positive for H. pylori by a urea breath test (UBT) to: 14 days of lansoprazole, amoxicillin, and clarithromycin (standard therapy); five days of lansoprazole, amoxicillin, clarithromycin, and metronidazole (concomitant therapy); or five days of lansoprazole and amoxicillin followed by five of lansoprazole, clarithromycin, and metronidazole (sequential therapy). Eradication was assessed by UBT six–eight weeks after randomisation. Findings In intention-to-treat analyses, the probability of eradication with standard therapy was 82·2%, which was 8·6% higher (95% adjusted CI: 2·6%, 14·5%) than with concomitant therapy (73·6%) and 5·6% higher (95% adjusted CI: −0·04%, 11·6%) than with sequential therapy (76·5%). In analyses limited to the 1314 participants who adhered to their assigned therapy, the probabilities of eradication were 87·1%, 78·7%, and 81·1% with standard, concomitant, and sequential therapies, respectively. Neither four-drug regimen was significantly better than standard triple therapy in any of the seven sites. Interpretation Standard 14-day triple-drug therapy is preferable to five-day concomitant or ten-day sequential four-drug regimens as empiric therapy for H. pylori among diverse Latin American populations. Funding Bill & Melinda Gates Foundation and US National Institutes of Health. PMID:21777974

Current and future pharmaceutical therapy for rheumatoid arthritis.

PubMed

Ruderman, Eric M

2005-01-01

Rheumatoid arthritis (RA) is a chronic, inflammatory arthritis with a population prevalence of approximately 1%. Pharmaceutical treatment includes both anti-inflammatory medications and disease modifying drugs (DMARDs) that impact the course of the damage associated with this disease. Traditional DMARD therapy includes immunomodulatory agents such as methotrexate, used both alone and in combination. Recently available biologic response modifiers are very effective at reducing both the clinical symptoms of disease and the radiographic damage that accompanies them. This manuscript describes the clinical assessments used to measure response to therapy in RA and reviews the results seen with the various treatment strategies in this disease. In addition, the clinical and structural outcomes seen in trials of newly available and pending biologic therapies are reviewed, along with the specific toxicity issues associated with these agents. Clinical trial data is reviewed for the TNF antagonists, which have become the standard of care in RA patients with an inadequate response to methotrexate. RA has been clearly shown to be a destructive and disabling disease. The widespread use of newer agents, however, along with more aggressive use of existing therapies, appears to limit disease progression very effectively, and should lead to better long-term outcomes for these patients.

What works in addiction treatment and what doesn't: is the best therapy no therapy?

PubMed

Peele, S

The current trend toward treating drug and alcohol (and other) addictions in disease-oriented, 12-step programs has had less success than most people believe. Treatments that teach coping skills, mobilize community forces, and instill values toward prosocial behavior have had success rates far superior to therapies that instruct individuals that they take drugs or drink excessively because they have a disease or because drugs are inherently addictive. Successful treatments instead deal with addicts' interactions with their environments and help them develop beliefs in their self-efficacy. Nonetheless, even addiction treatments which have demonstrated success face limitations in their ability to confront individual intentions and values, community standards, and environmental pressures and opportunities. At the same time, more individuals have quit addictions on their own than have been successfully treated by even the best therapies. Put simply, no therapy will ever be able in itself to make a substantial impact on our drug and alcohol or other addictive problems. In the meantime, addiction treatment is becoming more pervasive and coercive, and today holds out the possibility of corrupting our society and the self-conceptions of its members.

Stem cell transplantation as rescue therapy for refractory Crohn's disease: a sytematic review.

PubMed

Labidi, Asma; Serghini, Meriem; Ben Mustapha, Nadia; Fekih, Monia; Boubaker, Jalel; Filali, Azza

2014-11-01

Crohn's disease is a chronic relapsing- remitting affection. It has a strong immunologic component which represent the target of standard therapies including immunosppressants and biological therapies. However, many patients remain refracory or intolerant to these therapies. The aim of this review is to determine the effects of stem cell transplantation in patients with refractory Crohn's disease. Systematic review of observational studies, clinical trials and case reports that focused on the effectiveness and safety of stem cell transplantation in patients with refractory Crohn's disease. Hematopoietic stem cell transplantation seems to be efficient in maintaining clinical and endoscopic remission in patients with Crohn's disease refractory or intolerant to current therapies. However, it has been associated to high morbidity and mortality due to chemotherapy. Mesenchymal stem cell transplantation could induce remission in patients with fistulising refractory Crohns disease with no severe side effects. Its impact on luminal Crohns disease is still controversial. Stem cell transplantation seems to hold promising in patients with refractory Crohn's disease. However, because of the high morbidity and mortality related to chemotherapy, hematopoietic stem cell transplantation should be used as last resort to control this disease. Effectiveness of mesenchymal stem cell transplantation in luminal Crohn's disease has yet to be proven.

Host-directed therapies for infectious diseases: current status, recent progress, and future prospects.

PubMed

Zumla, Alimuddin; Rao, Martin; Wallis, Robert S; Kaufmann, Stefan H E; Rustomjee, Roxana; Mwaba, Peter; Vilaplana, Cris; Yeboah-Manu, Dorothy; Chakaya, Jeremiah; Ippolito, Giuseppe; Azhar, Esam; Hoelscher, Michael; Maeurer, Markus

2016-04-01

Despite extensive global efforts in the fight against killer infectious diseases, they still cause one in four deaths worldwide and are important causes of long-term functional disability arising from tissue damage. The continuing epidemics of tuberculosis, HIV, malaria, and influenza, and the emergence of novel zoonotic pathogens represent major clinical management challenges worldwide. Newer approaches to improving treatment outcomes are needed to reduce the high morbidity and mortality caused by infectious diseases. Recent insights into pathogen-host interactions, pathogenesis, inflammatory pathways, and the host's innate and acquired immune responses are leading to identification and development of a wide range of host-directed therapies with different mechanisms of action. Host-directed therapeutic strategies are now becoming viable adjuncts to standard antimicrobial treatment. Host-directed therapies include commonly used drugs for non-communicable diseases with good safety profiles, immunomodulatory agents, biologics (eg monoclonal antibodies), nutritional products, and cellular therapy using the patient's own immune or bone marrow mesenchymal stromal cells. We discuss clinically relevant examples of progress in identifying host-directed therapies as adjunct treatment options for bacterial, viral, and parasitic infectious diseases. Copyright © 2016 Elsevier Ltd. All rights reserved.

Innovations in energy expenditure assessment.

PubMed

Achamrah, Najate; Oshima, Taku; Genton, Laurence

2018-06-15

Optimal nutritional therapy has been associated with better clinical outcomes and requires providing energy as closed as possible to measured energy expenditure. We reviewed the current innovations in energy expenditure assessment in humans, focusing on indirect calorimetry and other new alternative methods. Although considered the reference method to measure energy expenditure, the use of indirect calorimetry is currently limited by the lack of an adequate device. However, recent technical developments may allow a broader use of indirect calorimetry for in-patients and out-patients. An ongoing international academic initiative to develop a new indirect calorimeter aimed to provide innovative and affordable technical solutions for many of the current limitations of indirect calorimetry. New alternative methods to indirect calorimetry, including CO2 measurements in mechanically ventilated patients, isotopic approaches and accelerometry-based fitness equipments, show promises but have been either poorly studied and/or are not accurate compared to indirect calorimetry. Therefore, to date, energy expenditure measured by indirect calorimetry remains the gold standard to guide nutritional therapy. Some new innovative methods are demonstrating promises in energy expenditure assessment, but still need to be validated. There is an ongoing need for easy-to-use, accurate and affordable indirect calorimeter for daily use in in-patients and out-patients.

Inhibition of the spindle assembly checkpoint kinase Mps-1 as a novel therapeutic strategy in malignant mesothelioma

PubMed Central

Szymiczek, Agata; Carbone, Michele; Pastorino, Sandra; Napolitano, Andrea; Tanji, Mika; Minaai, Michael; Pagano, Ian; Mason, Jacqueline M.; Pass, Harvey I.; Bray, Mark R.; Mak, Tak W.; Yang, Haining

2017-01-01

Malignant mesothelioma (MM) is an aggressive malignancy, highly resistant to current medical and surgical therapies, whose tumor cells characteristically show a high level of aneuploidy and genomic instability. We tested our hypothesis that targeting chromosomal instability in MM would improve response to therapy. TTK/Mps-1 (monopolar spindle 1 kinase) is a kinase of the spindle assembly checkpoint that controls cell division and cell fate. CFI-402257 is a novel, selective inhibitor of Mps-1 with antineoplastic activity. We found that CFI-402257 suppresses MM growth. We found that Mps-1 is overexpressed in MM and that its expression correlates with poor patients’ outcome. In vitro, CFI-402257-mediated inhibition of Mps-1 resulted in abrogation of the mitotic checkpoint, premature progression through mitosis, marked aneuploidy and mitotic catastrophe. In vivo, CFI-402257 reduced MM growth in an orthotopic, syngeneic model, when used as a single agent, and more so when used in combination with cisplatin+pemetrexed, the current standard of care. Our preclinical findings indicate that CFI-402257 is a promising novel therapeutic agent to improve the efficacy of the current chemotherapeutic regimens for MM patients. PMID:28759042

Predicting outcome following psychological therapy in IAPT (PROMPT): a naturalistic project protocol.

PubMed

Grant, Nina; Hotopf, Matthew; Breen, Gerome; Cleare, Anthony; Grey, Nick; Hepgul, Nilay; King, Sinead; Moran, Paul; Pariante, Carmine M; Wingrove, Janet; Young, Allan H; Tylee, André

2014-06-09

Depression and anxiety are highly prevalent and represent a significant and well described public health burden. Whilst first line psychological treatments are effective for nearly half of attenders, there remain a substantial number of patients who do not benefit. The main objective of the present project is to establish an infrastructure platform for the identification of factors that predict lack of response to psychological treatment for depression and anxiety, in order to better target treatments as well as to support translational and experimental medicine research in mood and anxiety disorders. Predicting outcome following psychological therapy in IAPT (PROMPT) is a naturalistic observational project that began patient recruitment in January 2014. The project is currently taking place in Southwark Psychological Therapies Service, an Improving Access to Psychological Therapies (IAPT) service currently provided by the South London and Maudsley NHS Foundation Trust (SLaM). However, the aim is to roll-out the project across other IAPT services. Participants are approached before beginning treatment and offered a baseline interview whilst they are waiting for therapy to begin. This allows us to test for relationships between predictor variables and patient outcome measures. At the baseline interview, participants complete a diagnostic interview; are asked to give blood and hair samples for relevant biomarkers, and complete psychological and social questionnaire measures. Participants then complete their psychological therapy as offered by Southwark Psychological Therapies Service. Response to psychological therapy will be measured using standard IAPT outcome data, which are routinely collected at each appointment. This project addresses a need to understand treatment response rates in primary care psychological therapy services for those with depression and/or anxiety. Measurement of a range of predictor variables allows for the detection of bio-psycho-social factors which may be relevant for treatment outcome. This will enable future clinical decision making to be based on the individual needs of the patient in an evidence-based manner. Moreover, the identification of individuals who fail to improve following therapy delivered by IAPT services could be utilised for the development of novel interventions.

78 FR 42975 - Notice Pursuant to the National Cooperative Research and Production Act of 1993-American Massage...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-18

... standards in cooperation with the Alliance for Massage Therapy Education, Associated Bodywork and Massage..., the Massage Therapy Foundation, and the National Certification Board for Therapeutic Massage and... training and education in massage therapy. AMTA's standards development activities are ongoing in nature...

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

USDA-ARS?s Scientific Manuscript database

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

Feasibility of a clinical trial of vision therapy for treatment of amblyopia.

PubMed

Lyon, Don W; Hopkins, Kristine; Chu, Raymond H; Tamkins, Susanna M; Cotter, Susan A; Melia, B Michele; Holmes, Jonathan M; Repka, Michael X; Wheeler, David T; Sala, Nicholas A; Dumas, Janette; Silbert, David I

2013-05-01

We conducted a pilot randomized clinical trial of office-based active vision therapy for the treatment of childhood amblyopia to determine the feasibility of conducting a full-scale randomized clinical trial. A training and certification program and manual of procedures were developed to certify therapists to administer a standardized vision therapy program in ophthalmology and optometry offices consisting of weekly visits for 16 weeks. Nineteen children, aged 7 to less than 13 years, with amblyopia (20/40-20/100) were randomly assigned to receive either 2 hours of daily patching with active vision therapy or 2 hours of daily patching with placebo vision therapy. Therapists in diverse practice settings were successfully trained and certified to perform standardized vision therapy in strict adherence with protocol. Subjects completed 85% of required weekly in-office vision therapy visits. Eligibility criteria based on age, visual acuity, and stereoacuity, designed to identify children able to complete a standardized vision therapy program and judged likely to benefit from this treatment, led to a high proportion of screened subjects being judged ineligible, resulting in insufficient recruitment. There were difficulties in retrieving adherence data for the computerized home therapy procedures. This study demonstrated that a 16-week treatment trial of vision therapy was feasible with respect to maintaining protocol adherence; however, recruitment under the proposed eligibility criteria, necessitated by the standardized approach to vision therapy, was not successful. A randomized clinical trial of in-office vision therapy for the treatment of amblyopia would require broadening of the eligibility criteria and improved methods to gather objective data regarding the home therapy. A more flexible approach that customizes vision therapy based on subject age, visual acuity, and stereopsis might be required to allow enrollment of a broader group of subjects.

Feasibility of a Clinical Trial of Vision Therapy for Treatment of Amblyopia

PubMed Central

Lyon, Don W.; Hopkins, Kristine; Chu, Raymond H.; Tamkins, Susanna M.; Cotter, Susan A.; Melia, B. Michele; Holmes, Jonathan M.; Repka, Michael X.; Wheeler, David T.; Sala, Nicholas A.; Dumas, Janette; Silbert, David I.

2013-01-01

Purpose We conducted a pilot randomized clinical trial of office-based active vision therapy for the treatment of childhood amblyopia to determine the feasibility of conducting a full-scale randomized clinical trial. Methods A training and certification program and manual of procedures were developed to certify therapists to administer a standardized vision therapy program in ophthalmology and optometry offices consisting of weekly visits for 16 weeks. Nineteen children, 7 to less than 13 years of age, with amblyopia (20/40–20/100) were randomly assigned to receive either 2 hours of daily patching with active vision therapy or 2 hours of daily patching with placebo vision therapy. Results Therapists in diverse practice settings were successfully trained and certified to perform standardized vision therapy in strict adherence with protocol. Subjects completed 85% of required weekly in-office vision therapy visits. Eligibility criteria based on age, visual acuity, and stereoacuity, designed to identify children able to complete a standardized vision therapy program and judged likely to benefit from this treatment, led to a high proportion of screened subjects being judged ineligible, resulting in insufficient recruitment. There were difficulties in retrieving adherence data for the computerized home therapy procedures. Conclusions This study demonstrated that a 16-week treatment trial of vision therapy was feasible with respect to maintaining protocol adherence; however, recruitment under the proposed eligibility criteria, necessitated by the standardized approach to vision therapy, was not successful. A randomized clinical trial of in-office vision therapy for the treatment of amblyopia would require broadening of the eligibility criteria and improved methods to gather objective data regarding the home therapy. A more flexible approach that customizes vision therapy based on subject age, visual acuity, and stereopsis, might be required to allow enrollment of a broader group of subjects. PMID:23563444

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

PubMed Central

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

2018-01-01

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

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

PubMed

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

2018-01-01

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

Analysis of glycosaminoglycans in cerebrospinal fluid from patients with mucopolysaccharidoses by isotope-dilution ultra-performance liquid chromatography-tandem mass spectrometry.

PubMed

Zhang, Haoyue; Young, Sarah P; Auray-Blais, Christiane; Orchard, Paul J; Tolar, Jakub; Millington, David S

2011-07-01

New therapies for the treatment of mucopolysaccharidoses that target the brain, including intrathecal enzyme replacement, are being explored. Quantitative analysis of the glycosaminoglycans (GAGs) that accumulate in these disorders is required to assess the disease burden and monitor the effect of therapy in affected patients. Because current methods lack the required limit of quantification and specificity to analyze GAGs in small volumes of cerebrospinal fluid (CSF), we developed a method based on ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Samples of CSF (25 μL) were evaporated to dryness and subjected to methanolysis. The GAGs were degraded to uronic acid-N-acetylhexosamine dimers and mixed with internal standards derived from deuteriomethanolysis of GAG standards. Specific dimers derived from heparan, dermatan and chondroitin sulfates (HS, DS and CS) were separated by UPLC and analyzed by electrospray ionization MS/MS using selected reaction monitoring for each targeted GAG product and its corresponding internal standard. CSF from control pediatric subjects (n = 22) contained <0.38 mg/L HS, 0.26 mg/L DS, and 2.8 mg/L CS, whereas CSF from patients with Hurler syndrome (n = 7) contained concentrations of DS and HS that were at least 6-fold greater than the upper control limits. These concentrations were reduced by 17.5% to 82.5% after allogeneic transplantation and treatment with intrathecal and intravenous enzyme replacement therapy. The method described here has potential value in monitoring patients with mucopolysaccharidoses receiving treatment targeted to the brain.

Efficacy and safety of oral alitretinoin in severe oral lichen planus--results of a prospective pilot study.

PubMed

Kunz, M; Urosevic-Maiwald, M; Goldinger, S M; Frauchiger, A L; Dreier, J; Belloni, B; Mangana, J; Jenni, D; Dippel, M; Cozzio, A; Guenova, E; Kamarachev, J; French, L E; Dummer, R

2016-02-01

Patients with severe oral lichen planus refractory to standard topical treatment currently have limited options of therapy suitable for long-term use. Oral alitretinoin (9-cis retinoic acid) was never systematically investigated in clinical trials, although case reports suggest its possible efficacy. To assess the efficacy and safety of oral alitretinoin taken at 30 mg once daily for up to 24 weeks in the treatment of severe oral lichen planus refractory to standard topical therapy. We conducted a prospective open-label single arm pilot study to test the efficacy and safety of 30 mg oral alitretinoin once daily for up to 24 weeks in severe oral lichen planus. Ten patients were included in the study. Primary end point was reduction in signs and symptoms measured by the Escudier severity score. Secondary parameters included pain and quality of life scores. Safety parameters were assessed during a follow-up period of 5 weeks. A substantial response at the end of treatment, i.e. >50% reduction in disease severity measured by the Escudier severity score, was apparent in 40% of patients. Therapy was well tolerated. Adverse events were mild and included headache, mucocutaneous dryness, musculoskeletal pain, increased thyroid-stimulating hormone and dyslipidaemia. Alitretinoin given at 30 mg daily reduced disease severity of severe oral lichen planus in a substantial proportion of patients refractory to standard treatment, was well tolerated and may thus represent one therapeutic option for this special group of patients. © 2015 European Academy of Dermatology and Venereology.

Standardization of definitions in focal therapy of prostate cancer: report from a Delphi consensus project.

PubMed

Postema, A W; De Reijke, T M; Ukimura, O; Van den Bos, W; Azzouzi, A R; Barret, E; Baumunk, D; Blana, A; Bossi, A; Brausi, M; Coleman, J A; Crouzet, S; Dominguez-Escrig, J; Eggener, S; Ganzer, R; Ghai, S; Gill, I S; Gupta, R T; Henkel, T O; Hohenfellner, M; Jones, J S; Kahmann, F; Kastner, C; Köhrmann, K U; Kovacs, G; Miano, R; van Moorselaar, R J; Mottet, N; Osorio, L; Pieters, B R; Polascik, T J; Rastinehad, A R; Salomon, G; Sanchez-Salas, R; Schostak, M; Sentker, L; Tay, K J; Varkarakis, I M; Villers, A; Walz, J; De la Rosette, J J

2016-10-01

To reach standardized terminology in focal therapy (FT) for prostate cancer (PCa). A four-stage modified Delphi consensus project was undertaken among a panel of international experts in the field of FT for PCa. Data on terminology in FT was collected from the panel by three rounds of online questionnaires. During a face-to-face meeting on June 21, 2015, attended by 38 experts, all data from the online rounds were reviewed and recommendations for definitions were formulated. Consensus was attained on 23 of 27 topics; Targeted FT was defined as a lesion-based treatment strategy, treating all identified significant cancer foci; FT was generically defined as an anatomy-based (zonal) treatment strategy. Treatment failure due to the ablative energy inadequately destroying treated tissue is defined as ablation failure. In targeting failure the energy is not adequately applied to the tumor spatially and selection failure occurs when a patient was wrongfully selected for FT. No definition of biochemical recurrence can be recommended based on the current data. Important definitions for outcome measures are potency (minimum IIEF-5 score of 21), incontinence (new need for pads or leakage) and deterioration in urinary function (increase in IPSS >5 points). No agreement on the best quality of life tool was established, but UCLA-EPIC and EORTC-QLQ-30 were most commonly supported by the experts. A complete overview of statements is presented in the text. Focal therapy is an emerging field of PCa therapeutics. Standardization of definitions helps to create comparable research results and facilitate clear communication in clinical practice.

Optimization of low-level light therapy's illumination parameters for spinal cord injury in a rat model

NASA Astrophysics Data System (ADS)

Shuaib, Ali; Bourisly, Ali

2018-02-01

Spinal cord injury (SCI) can result in complete or partial loss of sensation and motor function due to interruption along the severed axonal tract(s). SCI can result in tetraplegia or paraplegia, which can have prohibitive lifetime medical costs and result in shorter life expectancy. A promising therapeutic technique that is currently in experimental phase and that has the potential to be used to treat SCI is Low-level light therapy (LLLT). Preclinical studies have shown that LLLT has reparative and regenerative capabilities on transected spinal cords, and that LLLT can enhance axonal sprouting in animal models. However, despite the promising effects of LLLT as a therapy for SCI, it remains difficult to compare published results due to the use of a wide range of illumination parameters (i.e. different wavelengths, fluences, beam types, and beam diameter), and due to the lack of a standardized experimental protocol(s). Before any clinical applications of LLLT for SCI treatment, it is crucial to standardize illumination parameters and efficacy of light delivery. Therefore, in this study we aim to evaluate the light fluence distribution on a 3D voxelated SCI rat model with different illumination parameters (wavelengths: 660, 810, and 980 nm; beam types: Gaussian and Flat; and beam diameters: 0.1, 0.2, and 0.3 cm) for LLLT using Monte Carlo simulation. This study provides an efficient approach to guide researchers in optimizing the illumination parameters for LLLT spinal cord injury in an experimental model and will aid in quantitative and qualitative standardization of LLLT-SCI treatment.

A Case of Therapy-Related Acute Myeloid Leukemia Associated with Adjuvant Temozolomide Chemotherapy for Anaplastic Astrocytoma.

PubMed

Kosugi, Kenzo; Saito, Katsuya; Takahashi, Wataru; Tokuda, Yukina; Tomita, Hideyuki

2017-05-01

Temozolomide (TMZ) is now standard adjuvant therapy in combination with radiotherapy for patients with newly diagnosed malignant glioma. Treatment-related myelodysplastic syndrome and acute treatment-related leukemia (t-AML) associated with TMZ chemotherapy for patients with glioma is quite a rare complication. A 43-year-old man with an anaplastic astrocytoma received radiation therapy synchronized with ranimustine and adjuvant TMZ chemotherapy for 15 cycles. Close follow-up magnetic resonance imaging of the head during TMZ chemotherapy showed no evidence of tumor progression. One year after the completion of TMZ chemotherapy, a bone-marrow aspiration was performed because the patient's white blood cell count decreased. He was diagnosed with t-AML based on the bone marrow examination, and then he was referred to the cancer center for the treatment of t-AML. In this case study, we continued adjuvant TMZ therapy beyond the recommended 6 cycles. Currently, there is no consensus as to how long the adjuvant TMZ therapy should be continued for the treatment of residual tumor showing no apparent interval change. A new decision-making tool to assess the clinical benefits against the side effects for long-term adjuvant TMZ therapy is needed. Copyright © 2017 Elsevier Inc. All rights reserved.

Navigation through inter- and intratumoral heterogeneity of endocrine resistance mechanisms in breast cancer: A potential role for Liquid Biopsies?

PubMed

Reinhardt, Florian; Franken, André; Fehm, Tanja; Neubauer, Hans

2017-11-01

The majority of breast cancers are hormone receptor positive due to the expression of the estrogen and/or progesterone receptors. Endocrine therapy is a major treatment option for all disease stages of hormone receptor-positive breast cancer and improves overall survival. However, endocrine therapy is limited by de novo and acquired resistance. Several factors have been proposed for endocrine therapy failures, which include molecular alterations in the estrogen receptor pathway, altered expression of cell-cycle regulators, autophagy, and epithelial-to-mesenchymal transition as a consequence of tumor progression and selection pressure. It is essential to reveal and monitor intra- and intertumoral alterations in breast cancer to allow optimal therapy outcome. Endocrine therapy navigation by molecular profiling of tissue biopsies is the current gold standard but limited in many reasons. "Liquid biopsies" such as circulating-tumor cells and circulating-tumor DNA offer hope to fill that gap in allowing non-invasive serial assessment of biomarkers predicting success of endocrine therapy regimen. In this context, this review will provide an overview on inter- and intratumoral heterogeneity of endocrine resistance mechanisms and discuss the potential role of "liquid biopsies" as navigators to personalize treatment methods and prevent endocrine treatment resistance in breast cancer.

Design of clinical trials of gene therapy in Parkinson disease.

PubMed

Lewis, Travis B; Standaert, David G

2008-01-01

No current therapy for Parkinson disease has been shown to slow or reverse the progressive course of the disease. As a departure from traditional treatments, gene therapy approaches provide a new hope for realizing this long-sought goal; but before they can be widely employed for use in patients, they must first be submitted to the rigorous safety and efficacy standards of the clinical trial. Some of the challenges of gene therapy clinical trial design are similar to those in studies of conventional pharmacological agents and include addressing the heterogeneity of the disease, the need for clinical and surrogate endpoints, and the issue of distinguishing "symptomatic" from "neuroprotective" effects. Gene therapy trials also raise the issues of the risks of viral therapy, issues of dose-response, the need for sham surgery, and the long duration of risks and benefits. We conclude that the most feasible designs are for those treatments that are expected to produce a rapid improvement in directly observable symptoms. Trials of agents which are expected to produce only a slowing of progression and not a reversal of the disease course are likely to take much longer and will require the development of methods to assess quality of life and other non-motor aspects of the disease.

Radical Prostatectomy for Locally Advanced Prostate Cancers-Review of Literature.

PubMed

Srivatsa, N; Nagaraja, H; Shweta, S; Raghunath, S K

2017-06-01

Twenty-five to thirty percent of patients with prostate cancer present with locally advanced disease. While risk stratification remains the same with high incidence of upstaging of disease on imaging and histopathological evaluation; there have been progressive refinements in surgical therapy. With availability of reasonably robust data, radical prostatectomy in men with locally advanced prostate cancers seems to effect improvement in both cancer specific and overall survival rates in comparison to the current standard of care of radiation with androgen deprivation therapy. Studies using radical prostatectomy as a part of multimodality approach have also shown promising results. There is an imminent need for well-designed prospective studies of benefits of radical prostatectomy over radiation and androgen deprivation as well as benefits of multimodality therapy over monotherapy. Surgery for patients with locally advanced prostate cancer is technically challenging. Surgical outcomes are comparable to those of organ-confined disease when performed in high-volume centers. Neoadjuvant therapies prior to radical prostatectomy might improve surgical outcomes, but whether they will translate into a better cancer specific and overall survival are yet to be ascertained.

Adjuvant therapy for resected colon cancer 2017, including the IDEA analysis.

PubMed

Tang, Monica; Price, Timothy Jay; Shapiro, Jeremy; Gibbs, Peter; Haller, Daniel G; Arnold, Dirk; Peeters, Marc; Segelov, Eva; Roy, Amitesh; Tebbutt, Niall; Pavlakis, Nick; Karapetis, Chris; Burge, Matthew

2018-04-01

Oxaliplatin-based adjuvant chemotherapy has been the standard of care for resected early colon cancer for over a decade. Recent results from the IDEA meta-analysis attempt to address the question of whether 3 or 6 months of adjuvant chemotherapy is preferable in Stage III colon cancer. Areas covered: A review of the literature and recent conference presentations was undertaken on the topic of adjuvant therapy for resected early colon cancers. This article reviews the current evidence for adjuvant treatment of Stage II and III colon cancer, as well as up-to-date data regarding optimal duration of therapy. This article reviews the evidence for lifestyle modifications in the management of early colorectal cancer and other future directions for research in early colon cancer. Expert commentary: In recent years, there have been no advances in the development of novel agents for adjuvant therapy in colorectal cancer. Although the IDEA meta-analysis was negative for its primary non-inferiority endpoint, the detailed results provide valuable information that allows personalisation of treatment regimen and duration.

The Therapeutic Relationship in E-Therapy for Mental Health: A Systematic Review

PubMed Central

Schnur, Julie B; Constantino, Michael J; Miller, Sarah J; Brackman, Emily H; Montgomery, Guy H

2012-01-01

Background E-therapy is defined as a licensed mental health care professional providing mental health services via e-mail, video conferencing, virtual reality technology, chat technology, or any combination of these. The use of e-therapy has been rapidly expanding in the last two decades, with growing evidence suggesting that the provision of mental health services over the Internet is both clinically efficacious and cost effective. Yet there are still unanswered concerns about e-therapy, including whether it is possible to develop a successful therapeutic relationship over the Internet in the absence of nonverbal cues. Objective Our objective in this study was to systematically review the therapeutic relationship in e-therapy. Methods We searched PubMed, PsycINFO, and CINAHL through August 2011. Information on study methods and results was abstracted independently by the authors using a standardized form. Results From the 840 reviewed studies, only 11 (1.3%) investigated the therapeutic relationship. The majority of the reviewed studies were focused on the therapeutic alliance—a central element of the therapeutic relationship. Although the results do not allow firm conclusions, they indicate that e-therapy seems to be at least equivalent to face-to-face therapy in terms of therapeutic alliance, and that there is a relationship between the therapeutic alliance and e-therapy outcome. Conclusions Overall, the current literature on the role of therapeutic relationship in e-therapy is scant, and much more research is needed to understand the therapeutic relationship in online environments. PMID:22858538

The therapeutic relationship in e-therapy for mental health: a systematic review.

PubMed

Sucala, Madalina; Schnur, Julie B; Constantino, Michael J; Miller, Sarah J; Brackman, Emily H; Montgomery, Guy H

2012-08-02

E-therapy is defined as a licensed mental health care professional providing mental health services via e-mail, video conferencing, virtual reality technology, chat technology, or any combination of these. The use of e-therapy has been rapidly expanding in the last two decades, with growing evidence suggesting that the provision of mental health services over the Internet is both clinically efficacious and cost effective. Yet there are still unanswered concerns about e-therapy, including whether it is possible to develop a successful therapeutic relationship over the Internet in the absence of nonverbal cues. Our objective in this study was to systematically review the therapeutic relationship in e-therapy. We searched PubMed, PsycINFO, and CINAHL through August 2011. Information on study methods and results was abstracted independently by the authors using a standardized form. From the 840 reviewed studies, only 11 (1.3%) investigated the therapeutic relationship. The majority of the reviewed studies were focused on the therapeutic alliance-a central element of the therapeutic relationship. Although the results do not allow firm conclusions, they indicate that e-therapy seems to be at least equivalent to face-to-face therapy in terms of therapeutic alliance, and that there is a relationship between the therapeutic alliance and e-therapy outcome. Overall, the current literature on the role of therapeutic relationship in e-therapy is scant, and much more research is needed to understand the therapeutic relationship in online environments.

Intrahepatic Cholangiocarcinoma: expert consensus statement

PubMed Central

Weber, Sharon M; Ribero, Dario; O=Reilly, Eileen M; Kokudo, Norihiro; Miyazaki, Masaru; Pawlik, Timothy M

2015-01-01

An American Hepato-Pancreato-Biliary Association (AHPBA)-sponsored consensus meeting of expert panellists met on 15 January 2014 to review current evidence on the management of intrahepatic cholangiocarcinoma (ICC) in order to establish practice guidelines and to agree on consensus statements. The treatment of ICC requires a coordinated, multidisciplinary approach to optimize survival. Biopsy is not necessary if the surgeon suspects ICC and is planning curative resection, although biopsy should be obtained before systemic or locoregional therapies are initiated. Assessment of resectability is best accomplished using cross-sectional imaging [computed tomography (CT) or magnetic resonance imaging (MRI)], but the role of positron emission tomography (PET) is unclear. Resectability in ICC is defined by the ability to completely remove the disease while leaving an adequate liver remnant. Extrahepatic disease, multiple bilobar or multicentric tumours, and lymph node metastases beyond the primary echelon are contraindications to resection. Regional lymphadenectomy should be considered a standard part of surgical therapy. In patients with high-risk features, the routine use of diagnostic laparoscopy is recommended. The preoperative diagnosis of combined hepatocellular carcinoma and cholangiocarcinoma (cHCC–CC) by imaging studies is extremely difficult. Surgical resection remains the mainstay of treatment, but survival is worse than in HCC alone. There are no adequately powered, randomized Phase III trials that can provide definitive recommendations for adjuvant therapy for ICC. Patients with high-risk features (lymphovascular invasion, multicentricity or satellitosis, large tumours) should be encouraged to enrol in clinical trials and to consider adjuvant therapy. Cisplatin plus gemcitabine represents the standard-of-care, front-line systemic therapy for metastatic ICC. Genomic analyses of biliary cancers support the development of targeted therapeutic interventions. PMID:26172134

Use of compounded hormone therapy in the United States: report of The North American Menopause Society Survey.

PubMed

Gass, Margery L S; Stuenkel, Cynthia A; Utian, Wulf H; LaCroix, Andrea; Liu, James H; Shifren, Jan L

2015-12-01

A national survey was conducted to determine the extent of use of compounded hormone therapy (C-HT) and to characterize the differences between C-HT users and users of hormone therapy approved by the US Food and Drug Administration (FDA-HT users). This Internet survey enrolled 3,725 women aged 40 to 84 years who were postmenopausal or experiencing the menopause transition. The sample was weighted slightly by age, region, education, and race to reflect population attributes based on US Census data. Overall, 9% of women were current users of HT, and 28% of all respondents were ever-users of HT. C-HT users represented 31% of ever-users of HT, 35% of current users of HT, and 41% of ever-users aged 40 to 49 years. Approximately 13% of ever-users indicated current or past use of testosterone. The most cited reason for using HT was vasomotor symptoms (∼70%). Nonapproved indications for using HT were selected more often by C-HT users. There were four reports of endometrial cancer among the 326 C-HT users compared with none reported among the 738 FDA-HT users. Significance was not determined because of small numbers. This survey indicates substantial use of C-HT across the country and the possibility of higher rates of endometrial side effects with such products. There is a need for standardized data collection on the extent of use of compounded hormones and their potential risks.

Concise Review: The Clinical Application of Mesenchymal Stem Cells for Musculoskeletal Regeneration: Current Status and Perspectives

PubMed Central

Steinert, Andre F.; Rackwitz, Lars; Gilbert, Fabian; Nöth, Ulrich

2012-01-01

Regenerative therapies in the musculoskeletal system are based on the suitable application of cells, biomaterials, and/or factors. For an effective approach, numerous aspects have to be taken into consideration, including age, disease, target tissue, and several environmental factors. Significant research efforts have been undertaken in the last decade to develop specific cell-based therapies, and in particular adult multipotent mesenchymal stem cells hold great promise for such regenerative strategies. Clinical translation of such therapies, however, remains a work in progress. In the clinical arena, autologous cells have been harvested, processed, and readministered according to protocols distinct for the target application. As outlined in this review, such applications range from simple single-step approaches, such as direct injection of unprocessed or concentrated blood or bone marrow aspirates, to fabrication of engineered constructs by seeding of natural or synthetic scaffolds with cells, which were released from autologous tissues and propagated under good manufacturing practice conditions (for example, autologous chondrocyte implantation). However, only relatively few of these cell-based approaches have entered the clinic, and none of these treatments has become a “standard of care” treatment for an orthopaedic disease to date. The multifaceted reasons for the current status from the medical, research, and regulatory perspectives are discussed here. In summary, this review presents the scientific background, current state, and implications of clinical mesenchymal stem cell application in the musculoskeletal system and provides perspectives for future developments. PMID:23197783

Lipid-Based Drug Delivery Systems in Cancer Therapy: What Is Available and What Is Yet to Come

PubMed Central

Yingchoncharoen, Phatsapong; Kalinowski, Danuta S.

2016-01-01

Cancer is a leading cause of death in many countries around the world. However, the efficacy of current standard treatments for a variety of cancers is suboptimal. First, most cancer treatments lack specificity, meaning that these treatments affect both cancer cells and their normal counterparts. Second, many anticancer agents are highly toxic, and thus, limit their use in treatment. Third, a number of cytotoxic chemotherapeutics are highly hydrophobic, which limits their utility in cancer therapy. Finally, many chemotherapeutic agents exhibit short half-lives that curtail their efficacy. As a result of these deficiencies, many current treatments lead to side effects, noncompliance, and patient inconvenience due to difficulties in administration. However, the application of nanotechnology has led to the development of effective nanosized drug delivery systems known commonly as nanoparticles. Among these delivery systems, lipid-based nanoparticles, particularly liposomes, have shown to be quite effective at exhibiting the ability to: 1) improve the selectivity of cancer chemotherapeutic agents; 2) lower the cytotoxicity of anticancer drugs to normal tissues, and thus, reduce their toxic side effects; 3) increase the solubility of hydrophobic drugs; and 4) offer a prolonged and controlled release of agents. This review will discuss the current state of lipid-based nanoparticle research, including the development of liposomes for cancer therapy, different strategies for tumor targeting, liposomal formulation of various anticancer drugs that are commercially available, recent progress in liposome technology for the treatment of cancer, and the next generation of lipid-based nanoparticles. PMID:27363439

A randomised trial of povidone-iodine to reduce visual impairment from corneal ulcers in rural Nepal

PubMed Central

Katz, J; Khatry, S K; Thapa, M D; Schein, O D; Kimbrough Pradhan, E; LeClerq, S C; West , K P

2004-01-01

Aim: To assess whether povidone-iodine provided any benefit over and above a standard regimen of antibiotic therapy for the treatment of corneal ulcers. Methods: All patients diagnosed with corneal ulcers presenting for care at a primary eye care clinic in rural Nepal were randomised to a standard protocol of antibiotic therapy versus standard therapy plus 2.5% povidone-iodine every 2 hours for 2 weeks. The main outcomes were corrected visual acuity and presence, size, and position of corneal scarring in the affected eye at 2–4 months following treatment initiation. Results: 358 patients were randomised and 81% were examined at follow up. The two groups were comparable before treatment. At follow up, 3.9% in the standard therapy and 6.9% in the povidone-iodine group had corrected visual acuity worse than 20/400 (relative risk (RR) 1.77, 95% confidence interval (CI) 0.62 to 5.03). 9.4% in the standard therapy and 13.1% in the povidone-iodine group had corrected visual acuity worse than 20/60 (RR 1.39, 95% CI 0.71 to 2.77), and 17.0% and 18.8% had scars in the visual axis in each of these groups, respectively (RR 1.11, 95% CI 0.67 to 1.82). Conclusions: A small proportion of patients with corneal ulceration treated in this setting had poor visual outcomes. The addition of povidone-iodine to standard antibiotic therapy did not improve visual outcomes, although this design was unable to assess whether povidone-iodine on its own would have resulted in comparable visual outcomes to that of standard therapy. PMID:15548795

Subdissociative intranasal ketamine plus standard pain therapy versus standard pain therapy in the treatment of paediatric sickle cell disease vaso-occlusive crises in resource-limited settings: study protocol for a randomised controlled trial.

PubMed

Young, James R; Sawe, Hendry Robert; Mfinanga, Juma A; Nshom, Ernest; Helm, Ethan; Moore, Charity G; Runyon, Michael S; Reynolds, Stacy L

2017-07-10

Pediatric sickle cell disease, highly prevalent in sub-Saharan Africa, carries great morbidity and mortality risk. Limited resources and monitoring make management of acute vaso-occlusive crises challenging. This study aims to evaluate the efficacy and safety of subdissociative intranasal ketamine as a cheap, readily available and easily administered adjunct to standard pain therapy. We hypothesise that subdissociative, intranasal ketamine may significantly augment current approaches to pain management in resource-limited settings in a safe and cost-effective manner. This is a multicentred, randomised, double-blind, placebo-controlled trial enrolling children 4-16 years of age with sickle cell disease and painful vaso-occlusive pain crises. Study sites include two sub-Saharan teaching and referral hospitals with acute intake areas. All patients receive standard analgesic therapy during evaluation. Patients randomised to the treatment arm receive 1 mg/kg intranasal ketamine at onset of therapy, while placebo arm participants receive volume-matched intranasal normal saline. All participants and clinical staff are blinded to the treatment allocation. Data will be analysed on an intention-to-treat basis. Primary endpoints are changes in self-report pain scales (Faces Pain Scale-Revised) at 30, 60 and 120 minutes and rates of adverse events. Secondary endpoints include hospital length of stay, total analgesia use and quality of life assessment 2-3 weeks postintervention. The research methods for this study have been approved by the Cameroon Baptist Convention Health Board Institutional Review Board (IRB2015-07), the Tanzanian National Institute for Medical Research (NIMR/HQ/R.8a/Vol. IX/2299), Muhimbili National Hospital IRB (MNH/IRB/I/2015/14) and the Tanzanian Food and Drugs Authority (TFDA0015/CTR/0015/9). Data reports will be provided to the Data and Safety Monitoring Board (DSMB) periodically throughout the study as well as all reports of adverse events. All protocol amendments will also be reviewed by the DSMB. Study results, regardless of direction or amplitude, will be submitted for publication in relevant peer-reviewed journals. ClinicalTrials.Gov, NCT02573714. Date of registration: 8 October 2015. Pre-results. © 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.

Subdissociative intranasal ketamine plus standard pain therapy versus standard pain therapy in the treatment of paediatric sickle cell disease vaso-occlusive crises in resource-limited settings: study protocol for a randomised controlled trial

PubMed Central

Sawe, Hendry Robert; Mfinanga, Juma A; Nshom, Ernest; Helm, Ethan; Moore, Charity G; Runyon, Michael S; Reynolds, Stacy L

2017-01-01

Introduction Pediatric sickle cell disease, highly prevalent in sub-Saharan Africa, carries great morbidity and mortality risk. Limited resources and monitoring make management of acute vaso-occlusive crises challenging. This study aims to evaluate the efficacy and safety of subdissociative intranasal ketamine as a cheap, readily available and easily administered adjunct to standard pain therapy. We hypothesise that subdissociative, intranasal ketamine may significantly augment current approaches to pain management in resource-limited settings in a safe and cost-effective manner. Methods and analysis This is a multicentred, randomised, double-blind, placebo-controlled trial enrolling children 4–16 years of age with sickle cell disease and painful vaso-occlusive pain crises. Study sites include two sub-Saharan teaching and referral hospitals with acute intake areas. All patients receive standard analgesic therapy during evaluation. Patients randomised to the treatment arm receive 1 mg/kg intranasal ketamine at onset of therapy, while placebo arm participants receive volume-matched intranasal normal saline. All participants and clinical staff are blinded to the treatment allocation. Data will be analysed on an intention-to-treat basis. Primary endpoints are changes in self-report pain scales (Faces Pain Scale-Revised) at 30, 60 and 120 minutes and rates of adverse events. Secondary endpoints include hospital length of stay, total analgesia use and quality of life assessment 2–3 weeks postintervention. Ethics and dissemination The research methods for this study have been approved by the Cameroon Baptist Convention Health Board Institutional Review Board (IRB2015-07), the Tanzanian National Institute for Medical Research (NIMR/HQ/R.8a/Vol. IX/2299), Muhimbili National Hospital IRB (MNH/IRB/I/2015/14) and the Tanzanian Food and Drugs Authority (TFDA0015/CTR/0015/9). Data reports will be provided to the Data and Safety Monitoring Board (DSMB) periodically throughout the study as well as all reports of adverse events. All protocol amendments will also be reviewed by the DSMB. Study results, regardless of direction or amplitude, will be submitted for publication in relevant peer-reviewed journals. Trial registration ClinicalTrials.Gov, NCT02573714. Date of registration: 8 October 2015. Pre-results. PMID:28698351

Standardized definitions and clinical endpoints in carotid artery and supra-aortic trunk revascularization trials.

PubMed

Nedeltchev, Krassen; Pattynama, Peter M; Biaminoo, Giancarlo; Diehm, Nicolas; Jaff, Michael R; Hopkins, L Nelson; Ramee, Stephen; van Sambeek, Marc; Talen, Aly; Vermassen, Frank; Cremonesi, Alberto

2010-09-01

Endovascular therapy has emerged as a promising alternative to open surgery for stroke prevention in patients with obstructive disease of the supra-aortic arteries. Although most previous studies have used similar safety and efficacy endpoints, differences in definitions, timing of assessments, and standards of reporting have hampered direct comparisons across various trials. The DEFINE group, an informal collaboration of multidisciplinary physicians, involved in the therapy of patients with obstructive disease of the supra-aortic arteries in Europe and the United States reviewed the current literature and, after extensive correspondence and meetings, proposed the definitions outlined in the present manuscript. Three meetings including all authors of the manuscript, along with representatives of the United States Food and Drug Administration (FDA) and commercial device manufacturers were held in Barcelona, Spain, in May 2008, in Munich, Germany, in July 2008, and in New York in November 2008. The proposed definitions encompass baseline clinical and anatomic characteristics, clinical and radiologic outcomes, complications, standards of reporting, and timing of assessment. Considering the broad consensus between the multidisciplinary scientific members and the regulatory authorities, the proposed definitions are expected to find adoption in future clinical investigations. These definitions can be applied to both endovascular and open surgery trials and will allow reliable comparisons between these two revascularization methods.

Modelling the cost-utility of bio-electric stimulation therapy compared to standard care in the treatment of elderly patients with chronic non-healing wounds in the UK.

PubMed

Clegg, John P; Guest, Julian F

2007-04-01

To estimate the cost-utility of bio-electric stimulation therapy (Posifect) compared to standard care in elderly patients with chronic, non-healing wounds of > 6 months duration, from the perspective of the National Health Service (NHS) in the UK. Clinical and resource use data from a 16 week clinical evaluation of bio-electric stimulation therapy among patients who had recalcitrant wounds were combined with utility data obtained from a standard gamble analysis to construct a 16 week Markov model. The model considers the decision by a clinician to continue with a patient's previous care plan or treat with bio-electric stimulation therapy. Unit resource costs at 2005/2006 prices were applied to the resource utilisation estimates within the model, enabling the cost-utility of bio-electric stimulation therapy compared to standard care to be estimated. The acquisition cost of Posifect had not been decided at the time of performing this study. Hence, the base case analysis used a cost of 50 pounds per dressing. 33% of all wounds are expected to heal within 16 weeks after the start of bio-electric stimulation therapy. Consequently, using bio-electric stimulation therapy is expected to lead to a 51% decrease in the number of domiciliary clinician visits, from 4.7 to 2.3 per week. The model also showed that using bio-electric stimulation therapy instead of patients' standard care is expected to reduce the NHS cost of managing them by 16% from 2287 pounds (95% CI: 1838 pounds; 2735 pounds) to 1921 pounds (95% CI: 1609 pounds; 2233 pounds) and result in a health gain of 0.023 QALYs over 16 weeks. Hence, bio-electric stimulation therapy was found to be a dominant treatment. Sensitivity analyses demonstrated that the cost-utility of using bio-electric stimulation therapy relative to standard care is very sensitive to the acquisition cost of the therapy, the acquisition cost of patients' drugs and the number of clinician visits and less sensitive to utility values and the acquisition cost of other dressings. Within the limitations of the model, bio-electric stimulation therapy is expected to afford the NHS a cost-effective dressing compared to standard care in the management of chronic non-healing wounds of > 6 months duration. Bio-electric stimulation therapy's acquisition cost is expected to be offset by a reduction in the requirement for domiciliary clinician visits, leading to a release of NHS resources for use elsewhere in the system, thereby generating an increase in NHS efficiency.

Novel dietary supplement association reduces symptoms in endometriosis patients.

PubMed

Signorile, Pietro G; Viceconte, Rosa; Baldi, Alfonso

2018-08-01

Endometriosis is characterized by disabling symptoms that afflict young women with severe physical discomfort, difficulty in relationship life, and infertility; however, the currently available therapeutic strategies are unsatisfactory. Goal of this research was to identify a new combination of natural active ingredients that, administered as dietary supplements, could have the effect of reducing inflammatory response in endometriosis patients, decreasing the symptoms the disease produces and its harmful effects on affected organs. A cohort of endometriosis patient was treated for 3 months with a composition including quercitin, curcumin, parthenium, nicotinamide, 5-methyltetrahydrofolate, and omega 3/6. Using a VAS scale, we demonstrated a significant reduction of the symptoms in endometriosis patients treated with the dietary composition respect to the controls. Moreover, we demonstrated also a significant reduction in the serum levels of PGE2 and CA-125. Further study are required to compare the effect of this combination of molecules with standard therapies and to evaluate if the use of these dietary supplements in combination with standard therapies may lead to the improvement of the regular medical treatment for endometriosis. © 2017 Wiley Periodicals, Inc.

Neurobehavioral testing in subarachnoid hemorrhage: A review of methods and current findings in rodents.

PubMed

Turan, Nefize; Miller, Brandon A; Heider, Robert A; Nadeem, Maheen; Sayeed, Iqbal; Stein, Donald G; Pradilla, Gustavo

2017-11-01

The most important aspect of a preclinical study seeking to develop a novel therapy for neurological diseases is whether the therapy produces any clinically relevant functional recovery. For this purpose, neurobehavioral tests are commonly used to evaluate the neuroprotective efficacy of treatments in a wide array of cerebrovascular diseases and neurotrauma. Their use, however, has been limited in experimental subarachnoid hemorrhage studies. After several randomized, double-blinded, controlled clinical trials repeatedly failed to produce a benefit in functional outcome despite some improvement in angiographic vasospasm, more rigorous methods of neurobehavioral testing became critical to provide a more comprehensive evaluation of the functional efficacy of proposed treatments. While several subarachnoid hemorrhage studies have incorporated an array of neurobehavioral assays, a standardized methodology has not been agreed upon. Here, we review neurobehavioral tests for rodents and their potential application to subarachnoid hemorrhage studies. Developing a standardized neurobehavioral testing regimen in rodent studies of subarachnoid hemorrhage would allow for better comparison of results between laboratories and a better prediction of what interventions would produce functional benefits in humans.

Phase II trial of CH5424802 (alectinib hydrochloride) for recurrent or refractory ALK-positive anaplastic large cell lymphoma: study protocol for a non-randomized non-controlled trial.

PubMed

Nagai, Hirokazu; Fukano, Reiji; Sekimizu, Masahiro; Kada, Akiko; M Saito, Akiko; Asada, Ryuta; Mori, Tetsuya

2017-08-01

Currently, a standard therapy has not been established for recurrent or refractory anaplastic lymphoma kinase-positive anaplastic large cell lymphoma. While there are many treatment options, such as hematopoietic stem cell transplantation, patients with resistant disease to conventional chemotherapies have particularly poor prognosis. There is urgent need to develop new drugs because of the lack of a standard therapy and poor prognoses. This phase II trial is designed for evaluating the efficacy and safety of alectinib hydrochloride for patients with recurrent or refractory anaplastic lymphoma kinase -positive anaplastic large cell lymphoma. The primary endpoint is the response rate according to the Revised Response Criteria for Malignant Lymphoma. The secondary endpoints are pharmacokinetics, safety in children, complete response rate, response duration, progression-free survival, event-free survival, overall survival, and adverse events. The results of this trial will be the pivotal data for the drug approval of alectinib hydrochloride for recurrent or refractory anaplastic lymphoma kinase-positive anaplastic large cell lymphoma.

Do patterns of change during treatment for panic disorder predict future panic symptoms?

PubMed Central

Steinman, Shari A.; Hunter, Michael D.; Teachman, Bethany A.

2012-01-01

Background and Objectives Cognitive-behavioral therapies are currently the gold standard for panic disorder treatment, with well-documented treatment response. However, following interventions, some individuals continue to improve, while others experience a return of symptoms. The field lacks reliable ways to predict follow-up symptomology. In the current study, a cluster analysis with a repeated measures design was conducted to examine change patterns over 12 weeks of cognitive behavioral group therapy for panic disorder. The central aim of the study was to evaluate if change patterns predict level of panic symptom severity at a six month follow-up in this sample. Methods Individuals with panic disorder (N = 36) completed a measure of panic symptoms (Panic Disorder Severity Scale) at the outset of every therapy session and at a six month follow-up. Results Results revealed three patterns of change in this specific trial, which significantly predicted level of panic symptoms six months post-treatment, beyond initial or final level of panic symptoms, and beyond total symptom change. Limitations Given the relatively small, lab-based sample, replications in other settings and samples will be important. Conclusions Overall, results provide initial evidence that change patterns are meaningful predictors of panic symptom severity well after the final session of treatment. PMID:23187115

Treatment of Intravenous Leiomyomatosis with Cardiac Extension following Incomplete Resection.

PubMed

Doyle, Mathew P; Li, Annette; Villanueva, Claudia I; Peeceeyen, Sheen C S; Cooper, Michael G; Hanel, Kevin C; Fermanis, Gary G; Robertson, Greg

2015-01-01

Aim. Intravenous leiomyomatosis (IVL) with cardiac extension (CE) is a rare variant of benign uterine leiomyoma. Incomplete resection has a recurrence rate of over 30%. Different hormonal treatments have been described following incomplete resection; however no standard therapy currently exists. We review the literature for medical treatments options following incomplete resection of IVL with CE. Methods. Electronic databases were searched for all studies reporting IVL with CE. These studies were then searched for reports of patients with inoperable or incomplete resection and any further medical treatments. Our database was searched for patients with medical therapy following incomplete resection of IVL with CE and their results were included. Results. All studies were either case reports or case series. Five literature reviews confirm that surgery is the only treatment to achieve cure. The uses of progesterone, estrogen modulation, gonadotropin-releasing hormone antagonism, and aromatase inhibition have been described following incomplete resection. Currently no studies have reviewed the outcomes of these treatments. Conclusions. Complete surgical resection is the only means of cure for IVL with CE, while multiple hormonal therapies have been used with varying results following incomplete resection. Aromatase inhibitors are the only reported treatment to prevent tumor progression or recurrence in patients with incompletely resected IVL with CE.

Treatment of Intravenous Leiomyomatosis with Cardiac Extension following Incomplete Resection

PubMed Central

Doyle, Mathew P.; Li, Annette; Villanueva, Claudia I.; Peeceeyen, Sheen C. S.; Cooper, Michael G.; Hanel, Kevin C.; Fermanis, Gary G.; Robertson, Greg

2015-01-01

Aim. Intravenous leiomyomatosis (IVL) with cardiac extension (CE) is a rare variant of benign uterine leiomyoma. Incomplete resection has a recurrence rate of over 30%. Different hormonal treatments have been described following incomplete resection; however no standard therapy currently exists. We review the literature for medical treatments options following incomplete resection of IVL with CE. Methods. Electronic databases were searched for all studies reporting IVL with CE. These studies were then searched for reports of patients with inoperable or incomplete resection and any further medical treatments. Our database was searched for patients with medical therapy following incomplete resection of IVL with CE and their results were included. Results. All studies were either case reports or case series. Five literature reviews confirm that surgery is the only treatment to achieve cure. The uses of progesterone, estrogen modulation, gonadotropin-releasing hormone antagonism, and aromatase inhibition have been described following incomplete resection. Currently no studies have reviewed the outcomes of these treatments. Conclusions. Complete surgical resection is the only means of cure for IVL with CE, while multiple hormonal therapies have been used with varying results following incomplete resection. Aromatase inhibitors are the only reported treatment to prevent tumor progression or recurrence in patients with incompletely resected IVL with CE. PMID:26783463

Recurrent glioblastoma: Current patterns of care in an Australian population.

PubMed

Parakh, Sagun; Thursfield, Vicky; Cher, Lawrence; Dally, Michael; Drummond, Katharine; Murphy, Michael; Rosenthal, Mark A; Gan, Hui K

2016-02-01

This retrospective population-based survey examined current patterns of care for patients with recurrent glioblastoma (rGBM) who had previously undergone surgery and post-operative therapy at original diagnosis. The patients were identified from the Victorian Cancer Registry (VCR) from 2006 to 2008. Patient demographics, tumour characteristics and oncological management were extracted using a standardised survey by the treating clinicians/VCR staff and results analysed by the VCR. Kaplan-Meier estimates of overall survival (OS) at diagnosis and progression were calculated. A total of 95 patients (48%) received treatment for first recurrence; craniotomy and post-operative treatment (38), craniotomy only (34) and non-surgical treatment (23). Patients receiving treatment at first progression had a higher median OS than those who did not (7 versus 3 months, p<0.0001). All patients progressed after treatment for first progression with 43 patients (45%) receiving treatment at second progression. To our knowledge this is the first population-based pattern of care survey of treatment for rGBM in an era where post-operative "Stupp" chemo-radiation is standard. First and second line therapy for rGBM is common and associated with significant benefit. Treatment generally includes re-resection and/or systemic therapy. Copyright © 2015 Elsevier Ltd. All rights reserved.

Randomized Trial of Group Music Therapy With Chinese Prisoners: Impact on Anxiety, Depression, and Self-Esteem.

PubMed

Chen, Xi-Jing; Hannibal, Niels; Gold, Christian

2016-07-01

This study investigated the effects of group music therapy on improving anxiety, depression, and self-esteem in Chinese prisoners. Two-hundred male prisoners were randomly assigned to music therapy (n = 100) or standard care (n = 100). The music therapy had 20 sessions of group therapy compared with standard care. Anxiety (State and Trait Anxiety Inventory [STAI]), depression (Beck Depression Inventory [BDI]), and self-esteem (Texas Social Behavior Inventory [TSBI], Rosenberg Self-Esteem Inventory [RSI]) were measured by standardized scales at baseline, mid-program, and post-program. Data were analyzed based on the intention to treat principle. Compared with standard care, anxiety and depression in the music therapy condition decreased significantly at mid-test and post-test; self-esteem improved significantly at mid-test (TSBI) and at post-test (TSBI, RSI). Improvements were greater in younger participants (STAI-Trait, RSI) and/or in those with a lower level of education (STAI-State, STAI-Trait). Group music therapy seems to be effective in improving anxiety, depression, and self-esteem and was shown to be most beneficial for prisoners of younger age or with lower education level. © The Author(s) 2015.

Intravesical administration of combined hyaluronic acid (HA) and chondroitin sulfate (CS) for the treatment of female recurrent urinary tract infections: a European multicentre nested case-control study.

PubMed

Ciani, Oriana; Arendsen, Erik; Romancik, Martin; Lunik, Richard; Costantini, Elisabetta; Di Biase, Manuel; Morgia, Giuseppe; Fragalà, Eugenia; Roman, Tomaskin; Bernat, Marian; Guazzoni, Giorgio; Tarricone, Rosanna; Lazzeri, Massimo

2016-03-31

To compare the clinical effectiveness of the intravesical administration of combined hyaluronic acid and chondroitin sulfate (HA+CS) versus current standard management in adult women with recurrent urinary tract infections (RUTIs). A European Union-based multicentre, retrospective nested case-control study. 276 adult women treated for RUTIs starting from 2009 to 2013. Patients treated with either intravesical administration of HA+CS or standard of care (antimicrobial/immunoactive prophylaxis/probiotics/cranberry). The primary outcome was occurrence of bacteriologically confirmed recurrence within 12 months. Secondary outcomes were time to recurrence, total number of recurrences, health-related quality of life and healthcare resource consumption. Crude and adjusted results for unbalanced characteristics are presented. 181 patients treated with HA+CS and 95 patients treated with standard of care from 7 centres were included. The crude and adjusted ORs (95% CI) for the primary end point were 0.77 (0.46 to 1.28) and 0.51 (0.27 to 0.96), respectively. However, no evidence of improvement in terms of total number of recurrences (incidence rate ratio (95% CI), 0.99 (0.69 to 1.43)) or time to first recurrence was seen (HR (95% CI), 0.99 (0.61 to 1.61)). The benefit of intravesical HA+CS therapy improves when the number of instillations is ≥ 5. Our results show that bladder instillations of combined HA+CS reduce the risk of bacteriologically confirmed recurrences compared with the current standard management of RUTIs. Total incidence rates and hazard rates were instead non-significantly different between the 2 groups after adjusting for unbalanced factors. In contrast to what happens with antibiotic prophylaxis, the effectiveness of the HA+CS reinstatement therapy improves over time. NCT02016118. 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/

Effects of early combinatorial treatment of autologous split-thickness skin grafts in red duroc pig model using pulsed dye laser and fractional CO2 laser.

PubMed

Bailey, J Kevin; Blackstone, Britani N; DeBruler, Danielle M; Kim, Jayne Y; Baumann, Molly E; McFarland, Kevin L; Imeokparia, Folasade O; Supp, Dorothy M; Powell, Heather M

2018-01-01

The use of pulsed dye laser (PDL) and fractional CO 2 (FX CO 2 ) laser therapy to treat and/or prevent scarring following burn injury is becoming more widespread with a number of studies reporting reduction in scar erythema and pruritus following treatment with lasers. While the majority of studies report positive outcomes following PDL or FX CO 2 therapy, a number of studies have reported no benefit or worsening of the scar following treatment. The objective of this study was to directly compare the efficacy of PDL, FX CO 2 , and PDL + FX CO 2 laser therapy in reducing scarring post burn injury and autografting in a standardized animal model. Eight female red Duroc pigs (FRDP) received 4 standardized, 1 in. x 1 in. third degree burns that were excised and autografted. Wound sites were treated with PDL, FX CO 2 , or both at 4, 8, and 12 weeks post grafting. Grafts receiving no laser therapy served as controls. Scar appearance, morphology, size, and erythema were assessed and punch biopsies collected at weeks 4, 8, 12, and 16. At week 16, additional tissue was collected for biomechanical analyses and markers for inflammatory cytokines, extracellular matrix (ECM) proteins, re-epithelialization, pigmentation, and angiogenesis were quantified at all time points using qRT-PCR. Treatment with PDL, FX CO 2 , or PDL + FX CO 2 resulted in significantly less contraction versus skin graft only controls with no statistically significant difference among laser therapy groups. Scars treated with both PDL and FX CO 2 were visually more erythematous than other groups with a significant increase in redness between two and three standard deviations above normal skin redness. Scars treated with FX CO 2 were visually smoother and contained significantly fewer wrinkles. In addition, hyperpigmentation was significantly reduced in scars treated with FX CO 2 . The use of fractional carbon dioxide or pulsed dye laser therapy within 1 month of autografting significantly reduced scar contraction versus control, though no statistically significant difference was detected between laser modalities or use of both modalities. Overall, FX CO 2 therapy appears to be modestly more effective at reducing erythema, and improving scar texture and biomechanics. The current data adds to prior studies supporting the role of laser therapy in the treatment of burn scars and indicates more study is needed to optimize delivery protocols for maximum efficacy. Lasers Surg. Med. 50:78-87, 2018. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

A case of nosocomial Legionnaires' disease: The importance of early diagnosis, adequate prevention and eradication measures.

PubMed

Lucardie, A; Rogiers, Ph; Floré, K

2016-02-03

This case-report describes a patient with confirmed nosocomial Legionnaires' disease, a diagnosis which should be suspected when pneumonia does not respond to empiric therapy with beta-lactam antibiotics, or develops in the presence of certain risk factors. Culture is currently the golden standard for diagnosis, although the use of more modern techniques, such as a combination of urinary antigen testing and polymerase chain reaction, are on the rise. Specific detection and eradication methods are discussed.

Pneumocystis carinii pneumonia: a late presentation following treatment for stage IV neuroblastoma.

PubMed

Clarke, Edward; Glaser, Adam W; Picton, Susan V

2003-09-01

This report describes a child who develops Pneumocystis carinii pneumonia 7 months after high-dose chemotherapy for stage IV neuroblastoma. In addition to chemotherapy the child had also been treated with abdominal radiotherapy and 13-cis-retinoic acid. Standard practice has been to treat patients with prophylactic co-trimoxazole for 3 months after high-dose therapy, but this report highlights the intensity and complexity of current treatment for stage IV neuroblastoma and the need to be aware of prolonged lymphopenia after such treatment.

Assessment of Quality of Life in a Cohort of Newly Diagnosed Patients on HAART Regimen, in Resource Restricted Tribal Region of Chhattisgarh, India: A Prospective Study

PubMed Central

Singh, Harminder; Kaur, Kamalpreet; Dulhani, Navin; Bansal, Akash; Kumar, Bithika N.; Chouhan, Vinod Kumar Singh

2013-01-01

Background: Highly active antiretroviral therapy regimens have resulted in the systemic/clinical healing for human immune deficiency virus-infected patients but the consequence of antiretroviral therapy on the whole quality of life has become a major concern. The current study correlates the relationship of quality of life with successful highly active antiretroviral therapy. Aim: To determine the health-related quality of life in human immune deficiency virus-infected patients on highly active anti-retroviral therapy regimen in tribal region of Chhattisgarh. Design: An open label prospective study. Materials and Methods: Health-related quality of life was assessed using a standardized questionnaire, the Medical Outcomes Survey Short Form 36. Physical health summary scores and mental health summary scores were compared of pre-Highly Active Anti-Retroviral Therapy (at baseline) and post 12 months of therapy. Results: The increase in CD4 cell counts was extremely significant (P < 0.0001). The Physical Composite Summary (P value = 0.0003) improved significantly, whereas the Mental Composite Summary (with a baseline value of 40.7), post 12 months, was calculated as 42.8 (P value = 0.2371) and was statistically not significant. Conclusion: Efficacy measurement is the key ingredient of highly active anti-retroviral therapy, which must also include assessment of health-related quality of life to maximize the holistic approach towards disease. PMID:24049364

Effects of intensive glucose lowering in type 2 diabetes.

PubMed

Gerstein, Hertzel C; Miller, Michael E; Byington, Robert P; Goff, David C; Bigger, J Thomas; Buse, John B; Cushman, William C; Genuth, Saul; Ismail-Beigi, Faramarz; Grimm, Richard H; Probstfield, Jeffrey L; Simons-Morton, Denise G; Friedewald, William T

2008-06-12

Epidemiologic studies have shown a relationship between glycated hemoglobin levels and cardiovascular events in patients with type 2 diabetes. We investigated whether intensive therapy to target normal glycated hemoglobin levels would reduce cardiovascular events in patients with type 2 diabetes who had either established cardiovascular disease or additional cardiovascular risk factors. In this randomized study, 10,251 patients (mean age, 62.2 years) with a median glycated hemoglobin level of 8.1% were assigned to receive intensive therapy (targeting a glycated hemoglobin level below 6.0%) or standard therapy (targeting a level from 7.0 to 7.9%). Of these patients, 38% were women, and 35% had had a previous cardiovascular event. The primary outcome was a composite of nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes. The finding of higher mortality in the intensive-therapy group led to a discontinuation of intensive therapy after a mean of 3.5 years of follow-up. At 1 year, stable median glycated hemoglobin levels of 6.4% and 7.5% were achieved in the intensive-therapy group and the standard-therapy group, respectively. During follow-up, the primary outcome occurred in 352 patients in the intensive-therapy group, as compared with 371 in the standard-therapy group (hazard ratio, 0.90; 95% confidence interval [CI], 0.78 to 1.04; P=0.16). At the same time, 257 patients in the intensive-therapy group died, as compared with 203 patients in the standard-therapy group (hazard ratio, 1.22; 95% CI, 1.01 to 1.46; P=0.04). Hypoglycemia requiring assistance and weight gain of more than 10 kg were more frequent in the intensive-therapy group (P<0.001). As compared with standard therapy, the use of intensive therapy to target normal glycated hemoglobin levels for 3.5 years increased mortality and did not significantly reduce major cardiovascular events. These findings identify a previously unrecognized harm of intensive glucose lowering in high-risk patients with type 2 diabetes. (ClinicalTrials.gov number, NCT00000620.) 2008 Massachusetts Medical Society

Effects of Intensive Glucose Lowering in Type 2 Diabetes

PubMed Central

2015-01-01

Background Epidemiologic studies have shown a relationship between glycated hemoglobin levels and cardiovascular events in patients with type 2 diabetes. We investigated whether intensive therapy to target normal glycated hemoglobin levels would reduce cardiovascular events in patients with type 2 diabetes who had either established cardiovascular disease or additional cardiovascular risk factors. Methods In this randomized study, 10,251 patients (mean age, 62.2 years) with a median glycated hemoglobin level of 8.1% were assigned to receive intensive therapy (targeting a glycated hemoglobin level below 6.0%) or standard therapy (targeting a level from 7.0 to 7.9%). Of these patients, 38% were women, and 35% had had a previous cardiovascular event. The primary outcome was a composite of nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes. The finding higher mortality in the intensive-therapy group led to a discontinuation of intensive therapy after a mean of 3.5 years of follow-up. Results At 1 year, stable median glycated hemoglobin levels of 6.4% and 7.5% were achieved in the intensive-therapy group and the standard-therapy group, respectively. During follow-up, the primary outcome occurred in 352 patients in the intensive-therapy group, as compared with 371 in the standard-therapy group (hazard ratio, 0.90; 95% confidence interval [CI], 0.78 to 1.04; P = 0.16). At the same time, 257 patients in the intensive-therapy group died, as compared with 203 patients in the standard-therapy group (hazard ratio, 1.22; 95% CI, 1.01 to 1.46; P = 0.04). Hypoglycemia requiring assistance and weight gain of more than 10 kg were more frequent in the intensive-therapy group (P<0.001). Conclusions As compared with standard therapy, the use of intensive therapy to target normal glycated hemoglobin levels for 3.5 years increased mortality and did not significantly reduce major cardiovascular events. These findings identify a previously unrecognized harm of intensive glucose lowering in high-risk patients with type 2 diabetes. (ClinicalTrials.gov number, NCT00000620.) PMID:18539917

Pharmacotherapy of Acute Lung Injury and Acute Respiratory Distress Syndrome

PubMed Central

Raghavendran, Krishnan; Pryhuber, Gloria S.; Chess, Patricia R.; Davidson, Bruce A.; Knight, Paul R.; Notter, Robert H.

2009-01-01

Acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS) are characterized by rapid-onset respiratory failure following a variety of direct and indirect insults to the parenchyma or vasculature of the lungs. Mortality from ALI/ARDS is substantial, and current therapy primarily emphasizes mechanical ventilation and judicial fluid management plus standard treatment of the initiating insult and any known underlying disease. Current pharmacotherapy for ALI/ARDS is not optimal, and there is a significant need for more effective medicinal chemical agents for use in these severe and lethal lung injury syndromes. To facilitate future chemical-based drug discovery research on new agent development, this paper reviews present pharmacotherapy for ALI/ARDS in the context of biological and biochemical drug activities. The complex lung injury pathophysiology of ALI/ARDS offers an array of possible targets for drug therapy, including inflammation, cell and tissue injury, vascular dysfunction, surfactant dysfunction, and oxidant injury. Added targets for pharmacotherapy outside the lungs may also be present, since multiorgan or systemic pathology is common in ALI/ARDS. The biological and physiological complexity of ALI/ARDS requires the consideration of combined-agent treatments in addition to single-agent therapies. A number of pharmacologic agents have been studied individually in ALI/ARDS, with limited or minimal success in improving survival. However, many of these agents have complementary biological/biochemical activities with the potential for synergy or additivity in combination therapy as discussed in this article. PMID:18691048

Ocular melanoma: an overview of the current status

PubMed Central

Jovanovic, Predrag; Mihajlovic, Marija; Djordjevic-Jocic, Jasmina; Vlajkovic, Slobodan; Cekic, Sonja; Stefanovic, Vladisav

2013-01-01

Ocular melanoma is the second most common type of melanoma after cutaneous and the most common primary intraocular malignant tumor in adults. Large majority of ocular melanomas originate from uvea, while conjunctival melanomas are far less frequent. Incidence of uveal melanoma has remained stable over last three decades. Diagnosis is in most cases established by clinical examination with great accuracy. Local treatment of uveal melanoma has improved, with increased use of conservative methods and preservation of the eye, but survival rates have remained unchanged. Recent advances in cytogenetics and genetics enhanced prognostication and enabled to determine tumors with high metastatic potential. However, due to lack of effective systemic therapy, prognosis of patients with metastasis remains poor and metastatic disease remains the leading cause of death among patients with uveal melanoma. Conjunctival melanoma is rare, but its incidence is increasing. It mostly occurs among white adults. In majority of cases it originates from preceding primary acquired melanosis. Current standard treatment for conjunctival melanoma is wide local excision with adjuvant therapy, including brachytherapy, cryotherapy and topical application of chemotherapeutic agent. Rarity of this tumor limits conduction of controlled trials to define the best treatment modality. As well as for uveal melanoma, prognosis of patients with metastasis is poor because there is no effective systemic therapy. Better understanding of underlying genetic and molecular abnormalities implicated in development and progression of ocular melanomas provides a great opportunity for development of targeted therapy, which will hopefully improve prognosis of patients with metastatic disease. PMID:23826405

Combination Therapy with Cholinesterase Inhibitors and Memantine for Alzheimer’s Disease: A Systematic Review and Meta-Analysis

PubMed Central

Kishi, Taro; Iwata, Nakao

2015-01-01

Background: We performed an updated meta-analysis of randomized controlled trials of combination therapy with cholinesterase inhibitors and memantine in patients with Alzheimer’s disease. Methods: We reviewed cognitive function, activities of daily living, behavioral disturbance, global assessment, discontinuation rate, and individual side effects. Results: Seven studies (total n=2182) were identified. Combination therapy significantly affected behavioral disturbance scores (standardized mean difference=−0.13), activity of daily living scores (standardized mean difference=−0.10), and global assessment scores (standardized mean difference=−0.15). In addition, cognitive function scores (standardized mean difference=−0.13, P=.06) exhibited favorable trends with combination therapy. The effects of combination therapy were more significant in the moderate-to-severe Alzheimer’s disease subgroup in terms of all efficacy outcome scores. The discontinuation rate was similar in both groups, and there were no significant differences in individual side effects. Conclusions: Combination therapy was beneficial for the treatment of moderate-to-severe Alzheimer’s disease in terms of cognition, behavioral disturbances, activities of daily living, and global assessment was well tolerated. PMID:25548104

Combination therapy with cholinesterase inhibitors and memantine for Alzheimer's disease: a systematic review and meta-analysis.

PubMed

Matsunaga, Shinji; Kishi, Taro; Iwata, Nakao

2014-12-28

We performed an updated meta-analysis of randomized controlled trials of combination therapy with cholinesterase inhibitors and memantine in patients with Alzheimer's disease. We reviewed cognitive function, activities of daily living, behavioral disturbance, global assessment, discontinuation rate, and individual side effects. Seven studies (total n=2182) were identified. Combination therapy significantly affected behavioral disturbance scores (standardized mean difference=-0.13), activity of daily living scores (standardized mean difference=-0.10), and global assessment scores (standardized mean difference=-0.15). In addition, cognitive function scores (standardized mean difference=-0.13, P=.06) exhibited favorable trends with combination therapy. The effects of combination therapy were more significant in the moderate-to-severe Alzheimer's disease subgroup in terms of all efficacy outcome scores. The discontinuation rate was similar in both groups, and there were no significant differences in individual side effects. Combination therapy was beneficial for the treatment of moderate-to-severe Alzheimer's disease in terms of cognition, behavioral disturbances, activities of daily living, and global assessment was well tolerated. © The Author 2015. Published by Oxford University Press on behalf of CINP.

Play Therapy: A Review

ERIC Educational Resources Information Center

Porter, Maggie L.; Hernandez-Reif, Maria; Jessee, Peggy

2009-01-01

This article discusses the current issues in play therapy and its implications for play therapists. A brief history of play therapy is provided along with the current play therapy approaches and techniques. This article also touches on current issues or problems that play therapists may face, such as interpreting children's play, implementing…

[Current situation and thoughts on radiofrequency ablation in the treatment of thyroid cancers].

PubMed

Zhang, H; Dong, W W

2017-08-01

Radiofrequency ablation (RFA) was originally used primarily for the treatment of regional metastatic lymph nodes from recurrent thyroid cancers in the field of thyroid surgery. In recent years it is gradually used to treat a part of benign thyroid nodules. However, the domestic issues resulting from indiscriminately enlarged RFA indication and lack of standardization of therapy become more and more prominent, including initial treatment of operable thyroid cancers by RFA, which is against by the current consensus about RFA for patients with thyroid nodules and management guidelines for patients with thyroid cancers. Therefore, RFA should be avoided for initial treatment of operable thyroid cancers before the introduction of guidelines based on evidence-based medicine.

Randomized controlled clinical trial of yoga in the treatment of eating disorders.

PubMed

Carei, T Rain; Fyfe-Johnson, Amber L; Breuner, Cora C; Brown, Margaret A

2010-04-01

This was a pilot project designed to assess the effect of individualized yoga treatment on eating disorder outcomes among adolescents receiving outpatient care for diagnosed eating disorders (anorexia nervosa, bulimia nervosa, eating disorder not otherwise specified). A total of 50 girls and 4 boys aged 11-21 years were randomized to an 8-week trial of standard care vs. individualized yoga plus standard care. Of these, 27 were randomized to standard care and 26 to yoga plus standard care (attrition: n = 4). Standard care (every other week physician and/or dietician appointments) was required to meet ethical guidelines. The No Yoga group was offered yoga after study completion as an incentive to maintain participation. Outcomes evaluated at baseline, end of trial, and 1-month follow-up included Eating Disorder Examination (EDE), Body Mass Index (BMI), Beck Depression Inventory, State-Trait Anxiety Inventory, and Food Preoccupation questionnaire. The Yoga group demonstrated greater decreases in eating disorder symptoms. Specifically, the EDE scores decreased over time in the Yoga group, whereas the No Yoga group showed some initial decline but then returned to baseline EDE levels at week 12. Food preoccupation was measured before and after each yoga session, and decreased significantly after all sessions. Both groups maintained current BMI levels and decreased in anxiety and depression over time. Individualized yoga treatment decreased EDE scores at 12 weeks, and significantly reduced food preoccupation immediately after yoga sessions. Yoga treatment did not have a negative effect on BMI. Results suggest that individualized yoga therapy holds promise as adjunctive therapy to standard care. Copyright 2010 Society for Adolescent Medicine. Published by Elsevier Inc. All rights reserved.

A systematic review and meta-analysis of music therapy for the older adults with depression.

PubMed

Zhao, K; Bai, Z G; Bo, A; Chi, I

2016-11-01

To determine the efficacy of music therapy in the management of depression in the elderly. We conducted a systematic review and meta-analysis of randomized controlled trials. Change in depressive symptoms was measured with various scales. Standardized mean differences were calculated for each therapy-control contrast. A comprehensive search yielded 2,692 citations; 19 articles met inclusion criteria. Meta-analysis suggests that music therapy plus standard treatment has statistical significance in reducing depressive symptoms among older adults (standardized mean differences = 1.02; 95% CI = 0.87, 1.17). This systematic review and meta-analysis suggests that music therapy has an effect on reducing depressive symptoms to some extent. However, high-quality trials evaluating the effects of music therapy on depression are required. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

A Phase II randomised controlled trial assessing the feasibility, acceptability and potential effectiveness of dignity therapy for older people in care homes: study protocol.

PubMed

Hall, Sue; Chochinov, Harvey; Harding, Richard; Murray, Scott; Richardson, Alison; Higginson, Irene J

2009-03-24

Although most older people living in nursing homes die there, there is a dearth of robust evaluations of interventions to improve their end-of-life care. Residents usually have multiple health problems making them heavily reliant on staff for their care, which can erode their sense of dignity. Dignity Therapy has been developed to help promote dignity and reduce distress. It comprises a recorded interview, which is transcribed, edited then returned to the patient, who can bequeath it to people of their choosing. Piloting has suggested that Dignity Therapy is beneficial to people dying of cancer and their families. The aims of this study are to assess the feasibility, acceptability and potential effectiveness of Dignity Therapy to reduce psychological and spiritual distress in older people reaching the end of life in care homes, and to pilot the methods for a Phase III RCT. A randomised controlled open-label trial. Sixty-four residents of care homes for older people are randomly allocated to one of two groups: (i) Intervention (Dignity Therapy offered in addition to any standard care), and (ii) Control group (standard care). Recipients of the "generativity" documents are asked their views on taking part in the study and the therapy. Both quantitative and qualitative outcomes are assessed in face-to-face interviews at baseline and at approximately one and eight weeks after the intervention (equivalent in the control group). The primary outcome is residents' sense of dignity (potential effectiveness) assessed by the Patient Dignity Inventory. Secondary outcomes for residents include depression, hopefulness and quality of life. In view of the relatively small sample size, quantitative analysis is mainly descriptive. The qualitative analysis uses the Framework method. Dignity Therapy is brief, can be done at the bedside and could help both patients and their families. This detailed exploratory research shows if it is feasible to offer Dignity Therapy to residents of care homes, whether it is acceptable to them, their families and care home staff, if it is likely to be effective, and determine whether a Phase III RCT is desirable. Current Controlled Clinical Trials: ISRCTN37589515.

Time-resolved singlet-oxygen luminescence detection with an efficient and practical semiconductor single-photon detector

PubMed Central

Boso, Gianluca; Ke, Damei; Korzh, Boris; Bouilloux, Jordan; Lange, Norbert; Zbinden, Hugo

2015-01-01

In clinical applications, such as PhotoDynamic Therapy, direct singlet-oxygen detection through its luminescence in the near-infrared range (1270 nm) has been a challenging task due to its low emission probability and the lack of suitable single-photon detectors. Here, we propose a practical setup based on a negative-feedback avalanche diode detector that is a viable alternative to the current state-of-the art for different clinical scenarios, especially where geometric collection efficiency is limited (e.g. fiber-based systems, confocal microscopy, scanning systems etc.). The proposed setup is characterized with Rose Bengal as a standard photosensitizer and it is used to measure the singlet-oxygen quantum yield of a new set of photosensitizers for site-selective photodynamic therapy. PMID:26819830

Lifelong antiretroviral therapy or HIV cure: The benefits for the individual patient.

PubMed

Buell, Kevin G; Chung, Christopher; Chaudhry, Zain; Puri, Aiysha; Nawab, Khizr; Ravindran, Rahul Prashanth

2016-01-01

There are an estimated 35 million people living with human immunodeficiency virus (HIV) globally, 19 million of whom are unaware of their HIV status and, in the absence of antiretroviral therapy (ART), will have a shortened life expectancy. Although ART remains the "gold standard" for treatment of HIV infection, the requirement for lifelong treatment poses multiple challenges for the patient. These include stigma, an untenable pill burden, side effects, and the threat of viral resistance in the case of non-compliance. This review evaluates the challenges of accessing, delivering, and sustaining ART for people living with HIV and will discuss the case for pursuing a goal of HIV cure, the potential benefits of such a cure for the individual patient, and the current potential candidates for such a cure.

Angiogenic therapy for cardiac repair based on protein delivery systems.

PubMed

Formiga, F R; Tamayo, E; Simón-Yarza, T; Pelacho, B; Prósper, F; Blanco-Prieto, M J

2012-05-01

Cardiovascular diseases remain the first cause of morbidity and mortality in the developed countries and are a major problem not only in the western nations but also in developing countries. Current standard approaches for treating patients with ischemic heart disease include angioplasty or bypass surgery. However, a large number of patients cannot be treated using these procedures. Novel curative approaches under investigation include gene, cell, and protein therapy. This review focuses on potential growth factors for cardiac repair. The role of these growth factors in the angiogenic process and the therapeutic implications are reviewed. Issues including aspects of growth factor delivery are presented in relation to protein stability, dosage, routes, and safety matters. Finally, different approaches for controlled growth factor delivery are discussed as novel protein delivery platforms for cardiac regeneration.

Treatment strategies for Aspergillus infections.

PubMed

Chiller, Tom M.; Stevens, David A.

2000-04-01

Infections caused by Aspergillus species consist of many different disease presentations, ranging from relatively benign asthma in atopic disease to life-threatening systemic invasive infections. The spectrum of disease manifestations is determined by a combination of genetic predisposition, host immune system defects, and virulence of the Aspergillus species. For the purposes of this discussion, we will address three principal entities: invasive aspergillosis, both primary and disseminated, pulmonary aspergilloma, and allergic bronchopulmonary aspergillosis. Amphotericin B is the standard of treatment for severe Aspergillus infections, despite the fact that mortality in these patients remains high. Alternative therapies such as combination regimens and itraconazole also have efficacy against Aspergillus infections. We discuss the role of current therapies, the potential role of drugs in development, and the results of ongoing research with combination and immunotherapies. Copyright 2000 Harcourt Publishers Ltd.

Randomized trial of harp therapy during in vitro fertilization-embryo transfer.

PubMed

Murphy, Erin M; Nichols, Jennifer; Somkuti, Steve G; Sobel, Michael; Braverman, Andrea; Barmat, Larry I

2014-04-01

This study evaluated whether harp therapy reduces levels of stress and improves clinical outcomes in patients undergoing embryo transfer. This prospective randomized trial enrolled 181 women undergoing embryo transfer, who were randomized to harp therapy during embryo transfer or standard treatment. Patients underwent standardized psychological testing and physiologic assessment of stress. The study was conducted in a reproductive medicine practice. No statistically significant differences were found in the heart and respiratory rates, nor was there a significant difference in event-based anxiety at baseline. Harp therapy had a significantly larger decrease in state anxiety from pre- to post-embryo transfer. Clinical pregnancy was 53% versus 48% for the harp therapy and standard treatment groups, respectively. Harp therapy decreases state, or event-based, anxiety, significantly lowering state scores posttransfer and having a positive effect on acute levels of stress. There was an increased pregnancy rate, but larger sample sizes are needed to evaluate whether harp therapy has an effect on clinical outcomes.

Effects of Improvisational Music Therapy vs Enhanced Standard Care on Symptom Severity Among Children With Autism Spectrum Disorder

PubMed Central

Bieleninik, Łucja; Geretsegger, Monika; Mössler, Karin; Assmus, Jörg; Thompson, Grace; Gattino, Gustavo; Elefant, Cochavit; Gottfried, Tali; Igliozzi, Roberta; Muratori, Filippo; Suvini, Ferdinando; Kim, Jinah; Crawford, Mike J.; Odell-Miller, Helen; Oldfield, Amelia; Casey, Órla; Finnemann, Johanna; Carpente, John; Park, A-La; Grossi, Enzo

2017-01-01

Importance Music therapy may facilitate skills in areas affected by autism spectrum disorder (ASD), such as social interaction and communication. Objective To evaluate effects of improvisational music therapy on generalized social communication skills of children with ASD. Design, Setting, and Participants Assessor-blinded, randomized clinical trial, conducted in 9 countries and enrolling children aged 4 to 7 years with ASD. Children were recruited from November 2011 to November 2015, with follow-up between January 2012 and November 2016. Interventions Enhanced standard care (n = 182) vs enhanced standard care plus improvisational music therapy (n = 182), allocated in a 1:1 ratio. Enhanced standard care consisted of usual care as locally available plus parent counseling to discuss parents’ concerns and provide information about ASD. In improvisational music therapy, trained music therapists sang or played music with each child, attuned and adapted to the child’s focus of attention, to help children develop affect sharing and joint attention. Main Outcomes and Measures The primary outcome was symptom severity over 5 months, based on the Autism Diagnostic Observation Schedule (ADOS), social affect domain (range, 0-27; higher scores indicate greater severity; minimal clinically important difference, 1). Prespecified secondary outcomes included parent-rated social responsiveness. All outcomes were also assessed at 2 and 12 months. Results Among 364 participants randomized (mean age, 5.4 years; 83% boys), 314 (86%) completed the primary end point and 290 (80%) completed the last end point. Over 5 months, participants assigned to music therapy received a median of 19 music therapy, 3 parent counseling, and 36 other therapy sessions, compared with 3 parent counseling and 45 other therapy sessions for those assigned to enhanced standard care. From baseline to 5 months, mean ADOS social affect scores estimated by linear mixed-effects models decreased from 14.08 to 13.23 in the music therapy group and from 13.49 to 12.58 in the standard care group (mean difference, 0.06 [95% CI, −0.70 to 0.81]; P = .88), with no significant difference in improvement. Of 20 exploratory secondary outcomes, 17 showed no significant difference. Conclusions and Relevance Among children with autism spectrum disorder, improvisational music therapy, compared with enhanced standard care, resulted in no significant difference in symptom severity based on the ADOS social affect domain over 5 months. These findings do not support the use of improvisational music therapy for symptom reduction in children with autism spectrum disorder. Trial Registration isrctn.org Identifier: ISRCTN78923965 PMID:28787504

Effects of Improvisational Music Therapy vs Enhanced Standard Care on Symptom Severity Among Children With Autism Spectrum Disorder: The TIME-A Randomized Clinical Trial.

PubMed

Bieleninik, Lucja; Geretsegger, Monika; Mössler, Karin; Assmus, Jörg; Thompson, Grace; Gattino, Gustavo; Elefant, Cochavit; Gottfried, Tali; Igliozzi, Roberta; Muratori, Filippo; Suvini, Ferdinando; Kim, Jinah; Crawford, Mike J; Odell-Miller, Helen; Oldfield, Amelia; Casey, Órla; Finnemann, Johanna; Carpente, John; Park, A-La; Grossi, Enzo; Gold, Christian

2017-08-08

Music therapy may facilitate skills in areas affected by autism spectrum disorder (ASD), such as social interaction and communication. To evaluate effects of improvisational music therapy on generalized social communication skills of children with ASD. Assessor-blinded, randomized clinical trial, conducted in 9 countries and enrolling children aged 4 to 7 years with ASD. Children were recruited from November 2011 to November 2015, with follow-up between January 2012 and November 2016. Enhanced standard care (n = 182) vs enhanced standard care plus improvisational music therapy (n = 182), allocated in a 1:1 ratio. Enhanced standard care consisted of usual care as locally available plus parent counseling to discuss parents' concerns and provide information about ASD. In improvisational music therapy, trained music therapists sang or played music with each child, attuned and adapted to the child's focus of attention, to help children develop affect sharing and joint attention. The primary outcome was symptom severity over 5 months, based on the Autism Diagnostic Observation Schedule (ADOS), social affect domain (range, 0-27; higher scores indicate greater severity; minimal clinically important difference, 1). Prespecified secondary outcomes included parent-rated social responsiveness. All outcomes were also assessed at 2 and 12 months. Among 364 participants randomized (mean age, 5.4 years; 83% boys), 314 (86%) completed the primary end point and 290 (80%) completed the last end point. Over 5 months, participants assigned to music therapy received a median of 19 music therapy, 3 parent counseling, and 36 other therapy sessions, compared with 3 parent counseling and 45 other therapy sessions for those assigned to enhanced standard care. From baseline to 5 months, mean ADOS social affect scores estimated by linear mixed-effects models decreased from 14.08 to 13.23 in the music therapy group and from 13.49 to 12.58 in the standard care group (mean difference, 0.06 [95% CI, -0.70 to 0.81]; P = .88), with no significant difference in improvement. Of 20 exploratory secondary outcomes, 17 showed no significant difference. Among children with autism spectrum disorder, improvisational music therapy, compared with enhanced standard care, resulted in no significant difference in symptom severity based on the ADOS social affect domain over 5 months. These findings do not support the use of improvisational music therapy for symptom reduction in children with autism spectrum disorder. isrctn.org Identifier: ISRCTN78923965.

Response evaluation criteria for solid tumours in dogs (v1.0): a Veterinary Cooperative Oncology Group (VCOG) consensus document.

PubMed

Nguyen, S M; Thamm, D H; Vail, D M; London, C A

2015-09-01

In veterinary medical oncology, there is currently no standardized protocol for assessing response to therapy in solid tumours. The lack of such a formalized guideline makes it challenging to critically compare outcome measures across various treatment protocols. The Veterinary Cooperative Oncology Group (VCOG) membership consensus document presented here is based on the recommendations of a subcommittee of American College of Veterinary Internal Medicine (ACVIM) board-certified veterinary oncologists. This consensus paper has used the human response evaluation criteria in solid tumours (RECIST v1.1) as a framework to establish standard procedures for response assessment in canine solid tumours that is meant to be easy to use, repeatable and applicable across a variety of clinical trial structures in veterinary oncology. It is hoped that this new canine RECIST (cRECIST v1.0) will be adopted within the veterinary oncology community and thereby facilitate the comparison of current and future treatment protocols used for companion animals with cancer. © 2013 Blackwell Publishing Ltd.

Laparoscopic and Robotic Total Mesorectal Excision in the Treatment of Rectal Cancer. Brief Review and Personal Remarks

PubMed Central

Bianchi, Paolo Pietro; Petz, Wanda; Luca, Fabrizio; Biffi, Roberto; Spinoglio, Giuseppe; Montorsi, Marco

2014-01-01

The current standard treatment for rectal cancer is based on a multimodality approach with preoperative radiochemotherapy in advanced cases and complete surgical removal through total mesorectal excision (TME). The most frequent surgical approach is traditional open surgery, as laparoscopic TME requires high technical skill, a long learning curve, and is not widespread, still being confined to centers with great experience in minimally invasive techniques. Nevertheless, in several studies, the laparoscopic approach, when compared to open surgery, has shown some better short-term clinical outcomes and at least comparable oncologic results. Robotic surgery for the treatment of rectal cancer is an emerging technique, which could overcome some of the technical difficulties posed by standard laparoscopy, but evidence from the literature regarding its oncologic safety and clinical outcomes is still lacking. This brief review analyses the current status of minimally invasive surgery for rectal cancer therapy, focusing on oncologic safety and the new robotic approach. PMID:24834429

Incidence and management of arthralgias in breast cancer patients treated with aromatase inhibitors in an outpatient oncology clinic.

PubMed

Menas, Pamela; Merkel, Douglas; Hui, Wendy; Lawton, Jessica; Harper, Abigail; Carro, George

2012-12-01

Aromatase inhibitors (AIs) are routinely used as first-line adjuvant treatment of breast cancer in postmenopausal women with hormone receptor positive tumors. The current recommended length of treatment with an AI is 5 years. Arthralgias have been frequently cited as the primary reason for discontinuation of AI therapy. Various treatment strategies are proposed in literature, but a standardized treatment algorithm has not been established. The initial purpose of this study was to describe the incidence and management of AI-induced arthralgias in patients treated at Kellogg Cancer Center (KCC). Further evaluation led to the development and the implementation of a treatment algorithm and electronic medical record (EMR) documentation tools. The retrospective chart review included 206 adult patients with hormone receptor positive breast cancer who were receiving adjuvant therapy with an AI. A multidisciplinary treatment team consisting of pharmacists, collaborative practice nurses, and physicians met to develop a standardized treatment algorithm and corresponding EMR documentation tool. The treatment algorithm and documentation tool were developed after the study to better monitor and proactively treat patients with AI-induced arthralgias. RESULTS/ CONCLUSIONS: The overall incidence of arthralgias at KCC was 48% (n = 98/206). Of these patients, 32% were documented as having arthralgias within the first 6 months of therapy initiation. Patients who reported AI-induced arthralgias were younger than patients who did not report AI-induced arthralgias (61 vs. 65 years, p = 0.002). There was no statistical difference in the incidence of arthralgias in patients with a history of chemotherapy (including taxane therapy) compared to those who did not receive chemotherapy (p = 0.352). Of patients presenting with AI-induced arthralgias, 41% did not have physician-managed treatment documented in the EMR. A standardized treatment algorithm and electronic chart documentation tools were then developed by the multidisciplinary team.

Cost-effectiveness of alternative smoking cessation scenarios in Spain: results from the EQUIPTMOD.

PubMed

Trapero-Bertran, Marta; Muñoz, Celia; Coyle, Kathryn; Coyle, Doug; Lester-George, Adam; Leidl, Reiner; Németh, Bertalan; Cheung, Kei-Long; Pokhrel, Subhash; Lopez-Nicolás, Ángel

2018-03-13

To assess the cost-effectiveness of alternative smoking cessation scenarios from the perspective of the Spanish National Health Service (NHS). We used the European study on Quantifying Utility of Investment in Protection from Tobacco model (EQUIPTMOD), a Markov-based state transition economic model, to estimate the return on investment (ROI) of: (a) the current provision of smoking cessation services (brief physician advice and printed self-helped material + smoking ban and tobacco duty at current levels); and (b) four alternative scenarios to complement the current provision: coverage of proactive telephone calls; nicotine replacement therapy (mono and combo) [prescription nicotine replacement therapy (Rx NRT)]; varenicline (standard duration); or bupropion. A rate of 3% was used to discount life-time costs and benefits. Spain. Adult smoking population (16+ years). Health-care costs associated with treatment of smoking attributable diseases (lung cancer, coronary heart disease, chronic obstructive pulmonary infection and stroke); intervention costs; quality-adjusted life years (QALYs). Costs and outcomes were summarized using various ROI estimates. The cost of implementing the current provision of smoking cessation services is approximately €61 million in the current year. This translates to 18 quitters per 1000 smokers and a life-time benefit-cost ratio of 5, compared with no such provision. All alternative scenarios were dominant (cost-saving: less expensive to run and generated more QALYs) from the life-time perspective, compared with the current provision. The life-time benefit-cost ratios were: 1.87 (proactive telephone calls); 1.17 (Rx NRT); 2.40 (varenicline-standard duration); and bupropion (2.18). The results remained robust in the sensitivity analysis. According to the EQUIPTMOD modelling tool it would be cost-effective for the Spanish authorities to expand the reach of existing GP brief interventions for smoking cessation, provide pro-active telephone support, and reimburse smoking cessation medication to smokers trying to stop. Such policies would more than pay for themselves in the long run. © 2018 The Authors. Addiction published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.

Extra-Pulmonary Tuberculosis and Its Surgical Treatment.

PubMed

Fry, Donald E

2016-08-01

Tuberculous infection has declined in the United States but remains a major infectious disease with morbidity and death for millions of people. Although the primary therapy is drugs, complications of the disease require surgical interventions. The published literature on tuberculosis was reviewed to provide a current understanding of the medical treatment of the disease and to define those areas where surgical intervention continues to be necessary. Multi-drug therapy for tuberculosis has become the standard and has reduced the complications of the disease necessitating surgical intervention. However, multi-drug resistance and extensively drug-resistant tuberculosis continue to be major problems and require effective initial therapy with surveillance to define resistant infections. The roles of surgery in tuberculosis are in establishing the diagnosis in extra-pulmonary infection and in the management of complications of disseminated disease. Tuberculosis remains an occupational risk for surgeons and surgical personnel. Tuberculosis is still a global problem, mandating recognition and treatment. Surgeons should have an understanding of the diverse presentation and complications of the disease.

Spotlight on opicapone as an adjunct to levodopa in Parkinson’s disease: design, development and potential place in therapy

PubMed Central

Annus, Ádám; Vécsei, László

2017-01-01

Parkinson’s disease (PD) is a progressive, chronic, neurodegenerative disease characterized by rigidity, tremor, bradykinesia and postural instability secondary to dopaminergic deficit in the nigrostriatal system. Currently, disease-modifying therapies are not available, and levodopa (LD) treatment remains the gold standard for controlling motor and nonmotor symptoms of the disease. LD is extensively and rapidly metabolized by peripheral enzymes, namely, aromatic amino acid decarboxylase and catechol-O-methyltransferase (COMT). To increase the bioavailability of LD, COMT inhibitors are frequently used in clinical settings. Opicapone is a novel COMT inhibitor that has been recently approved by the European Medicines Agency as an adjunctive therapy to combinations of LD and aromatic amino acid decarboxylase inhibitor in adult PD patients with end-of-dose motor fluctuations. We aimed to review the biochemical properties of opicapone, summarize its preclinical and clinical trials and discuss its future potential role in the treatment of PD. PMID:28123288

The cutaneous bacterium Janthinobacterium lividum inhibits the growth of Trichophyton rubrum in vitro.

PubMed

Ramsey, Jeremy P; Mercurio, Albert; Holland, Jessica A; Harris, Reid N; Minbiole, Kevin P C

2015-02-01

Tinea pedis (athlete's foot) is a fungal infection that is both widespread and challenging to treat. Standard treatments consist of topical and systemic therapies of antifungal agents, such as miconazole, itraconazole, and terbinafine. The extended nature of topical therapy and the toxicity of long-term systemic therapy limit the utility of current treatments. An alternate approach relies on an understanding of bacterial-fungal interactions. Specifically, a probiotic antifungal bacterium such as Janthinobacterium lividum can counter infection; Janthinobacterium is a major constituent of the human skin microbiota. Janthinobacterium lividum has been shown to ameliorate the effects of the cutaneous fungal disease chytridiomycosis in a vertebrate species (Rana muscosa). Dual-culture plate challenge assays were performed using J. lividum and Trichophyton rubrum, the leading cause of athlete's foot. In all cases, T. rubrum colonies grew significantly smaller when co-cultured with J. lividum. These in vitro results suggest that J. lividum merits further investigation as a human cutaneous probiotic. © 2013 The International Society of Dermatology.

Electrical stimulation for gastroesophageal reflux disease: current state of the art.

PubMed

Kim, Sharon E; Soffer, Edy

2016-01-01

Patients with gastroesophageal reflux disease (GERD) who are not satisfied with acid suppression therapy can benefit primarily from fundoplication, a surgical intervention. Fundoplication has been the standard surgical procedure for GERD. It is effective but is associated with adverse effects, resulting in a declining number of interventions, creating a need for alternative interventions that are effective, yet have a better adverse effect profile. One such alternative involves the application of electrical stimulation to the lower esophageal sphincter. A number of animal studies showed that such stimulation can increase resting lower esophageal sphincter pressure. An acute human study confirmed this effect, and was followed by two open-label studies, with a follow-up of up to 3 years. Results thus far show that the therapy is associated with a significant improvement in symptoms, a significant reduction in esophageal acid exposure, and a very good safety profile. This review will describe the evolution of electrical stimulation therapy for GERD, as well as the safety and efficacy of this intervention.

Economic Evaluation of Pharmaco- and Behavioral Therapies for Smoking Cessation: A Critical and Systematic Review of Empirical Research

PubMed Central

Ruger, Jennifer Prah; Lazar, Christina M.

2014-01-01

Economic evaluations are an important tool to improve our understanding of the costs and effects of health care services and to create sustainable health care systems. This article critically assesses empirical evidence from economic evaluations of pharmaco- and behavioral therapies for smoking cessation. A comprehensive literature review of PubMed and the British National Health Service Economic Evaluation Database was conducted. The search identified 15 articles on nicotine-based pharmacotherapies, 12 articles on nonnicotine based pharmacotherapies, no articles on selegiline, and 10 articles on brief counseling for smoking cessation treatment. Results show that both pharmaco- and behavioral therapies for smoking cessation are cost-effective or even cost-saving. The review highlights several shortcomings in methodology and a lack of standardization of current economic evaluations. Efforts to improve methodology will help make future studies more comparable and increase the evidence base so that such evaluations can be more useful to public health practitioners and policy makers. PMID:22224889

Using Acellular Bioactive Extracellular Matrix Scaffolds to Enhance Endogenous Cardiac Repair

PubMed Central

Svystonyuk, Daniyil A.; Mewhort, Holly E. M.; Fedak, Paul W. M.

2018-01-01

An inability to recover lost cardiac muscle following acute ischemic injury remains the biggest shortcoming of current therapies to prevent heart failure. As compared to standard medical and surgical treatments, tissue engineering strategies offer the promise of improved heart function by inducing regeneration of functional heart muscle. Tissue engineering approaches that use stem cells and genetic manipulation have shown promise in preclinical studies but have also been challenged by numerous critical barriers preventing effective clinical translational. We believe that surgical intervention using acellular bioactive ECM scaffolds may yield similar therapeutic benefits with minimal translational hurdles. In this review, we outline the limitations of cellular-based tissue engineering strategies and the advantages of using acellular biomaterials with bioinductive properties. We highlight key anatomic targets enriched with cellular niches that can be uniquely activated using bioactive scaffold therapy. Finally, we review the evolving cardiovascular tissue engineering landscape and provide critical insights into the potential therapeutic benefits of acellular scaffold therapy. PMID:29696148

State of the Art for Deep Brain Stimulation Therapy in Movement Disorders: A Clinical and Technological Perspective.

PubMed

Wagle Shukla, Aparna; Okun, Michael S

2016-01-01

Deep brain stimulation (DBS) therapy is a widely used brain surgery that can be applied for many neurological and psychiatric disorders. DBS is American Food and Drug Administration approved for medication refractory Parkinson's disease, essential tremor and dystonia. Although DBS has shown consistent success in many clinical trials, the therapy has limitations and there are well-recognized complications. Thus, only carefully selected patients are ideal candidates for this surgery. Over the last two decades, there have been significant advances in clinical knowledge on DBS. In addition, the surgical techniques and technology related to DBS has been rapidly evolving. The goal of this review is to describe the current status of DBS in the context of movement disorders, outline the mechanisms of action for DBS in brief, discuss the standard surgical and imaging techniques, discuss the patient selection and clinical outcomes in each of the movement disorders, and finally, introduce the recent advancements from a clinical and technological perspective.

The effects of complementary and alternative medicine on the speech of patients with depression

NASA Astrophysics Data System (ADS)

Fraas, Michael; Solloway, Michele

2004-05-01

It is well documented that patients suffering from depression exhibit articulatory timing deficits and speech that is monotonous and lacking pitch variation. Traditional remediation of depression has left many patients with adverse side effects and ineffective outcomes. Recent studies indicate that many Americans are seeking complementary and alternative forms of medicine to supplement traditional therapy approaches. The current investigation wishes to determine the efficacy of complementary and alternative medicine (CAM) on the remediation of speech deficits associated with depression. Subjects with depression and normal controls will participate in an 8-week treatment session using polarity therapy, a form of CAM. Subjects will be recorded producing a series of spontaneous and narrative speech samples. Acoustic analysis of mean fundamental frequency (F0), variation in F0 (standard deviation of F0), average rate of F0 change, and pause and utterance durations will be conducted. Differences pre- and post-CAM therapy between subjects with depression and normal controls will be discussed.

Improving practice in community-based settings: a randomized trial of supervision - study protocol.

PubMed

Dorsey, Shannon; Pullmann, Michael D; Deblinger, Esther; Berliner, Lucy; Kerns, Suzanne E; Thompson, Kelly; Unützer, Jürgen; Weisz, John R; Garland, Ann F

2013-08-10

Evidence-based treatments for child mental health problems are not consistently available in public mental health settings. Expanding availability requires workforce training. However, research has demonstrated that training alone is not sufficient for changing provider behavior, suggesting that ongoing intervention-specific supervision or consultation is required. Supervision is notably under-investigated, particularly as provided in public mental health. The degree to which supervision in this setting includes 'gold standard' supervision elements from efficacy trials (e.g., session review, model fidelity, outcome monitoring, skill-building) is unknown. The current federally-funded investigation leverages the Washington State Trauma-focused Cognitive Behavioral Therapy Initiative to describe usual supervision practices and test the impact of systematic implementation of gold standard supervision strategies on treatment fidelity and clinical outcomes. The study has two phases. We will conduct an initial descriptive study (Phase I) of supervision practices within public mental health in Washington State followed by a randomized controlled trial of gold standard supervision strategies (Phase II), with randomization at the clinician level (i.e., supervisors provide both conditions). Study participants will be 35 supervisors and 130 clinicians in community mental health centers. We will enroll one child per clinician in Phase I (N = 130) and three children per clinician in Phase II (N = 390). We use a multi-level mixed within- and between-subjects longitudinal design. Audio recordings of supervision and therapy sessions will be collected and coded throughout both phases. Child outcome data will be collected at the beginning of treatment and at three and six months into treatment. This study will provide insight into how supervisors can optimally support clinicians delivering evidence-based treatments. Phase I will provide descriptive information, currently unavailable in the literature, about commonly used supervision strategies in community mental health. The Phase II randomized controlled trial of gold standard supervision strategies is, to our knowledge, the first experimental study of gold standard supervision strategies in community mental health and will yield needed information about how to leverage supervision to improve clinician fidelity and client outcomes. ClinicalTrials.gov NCT01800266.

Shockwave treatment for medial tibial stress syndrome: A randomized double blind sham-controlled pilot trial.

PubMed

Newman, Phil; Waddington, Gordon; Adams, Roger

2017-03-01

Up to 35% of runners develop medial tibial stress syndrome (MTSS) which often results in lengthy disruption to training and sometimes affects daily activities. There is currently no high quality evidence to support any particular intervention for MTSS. This study aims to investigate the effect of shockwave therapy for MTSS. A randomized, sham-controlled, pilot trial in a university-based health clinic including 28 active adults with MTSS. Intervention included standard dose shockwave therapy for the experimental group versus sham dose for the control group, delivered during Week 1-3, 5 and 9. Main outcome measures were pain measured during bone and muscle pressure as well as during running using a numerical rating scale (0-10) and running was measured as pain-limited distance (m), at Week 1 (baseline) and Week 10 (post-intervention). Self-perception of change was measured using the Global Rating of Change Scale (-7 to +7) at Week 10 (post-intervention). Pain (palpation) was reduced in the experimental group by 1.1 out of 10.0 (95% CI -2.3 to 0.0) less than the control group. There were no other statistically significant differences between the groups. Standard dose shockwave therapy is not more effective than sham dose at improving pain or running distance in MTSS. However, the sham dose may have had a clinical effect. Further investigation including a no intervention control is warranted to evaluate the effect of shockwave therapy in the management of MTSS. Copyright © 2016 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

Defining Clinical Response Criteria and Early Response Criteria for Precision Oncology: Current State-of-the-Art and Future Perspectives.

PubMed

Subbiah, Vivek; Chuang, Hubert H; Gambhire, Dhiraj; Kairemo, Kalevi

2017-02-15

In this era of precision oncology, there has been an exponential growth in the armamentarium of genomically targeted therapies and immunotherapies. Evaluating early responses to precision therapy is essential for "go" versus "no go" decisions for these molecularly targeted drugs and agents that arm the immune system. Many different response assessment criteria exist for use in solid tumors and lymphomas. We reviewed the literature using the Medline/PubMed database for keywords "response assessment" and various known response assessment criteria published up to 2016. In this article we review the commonly used response assessment criteria. We present a decision tree to facilitate selection of appropriate criteria. We also suggest methods for standardization of various response assessment criteria. The relevant response assessment criteria were further studied for rational of development, key features, proposed use and acceptance by various entities. We also discuss early response evaluation and provide specific case studies of early response to targeted therapy. With high-throughput, advanced computing programs and digital data-mining it is now possible to acquire vast amount of high quality imaging data opening up a new field of "omics in radiology"-radiomics that complements genomics for personalized medicine. Radiomics is rapidly evolving and is still in the research arena. This cutting-edge technology is poised to move soon to the mainstream clinical arena. Novel agents with new mechanisms of action require advanced molecular imaging as imaging biomarkers. There is an urgent need for development of standardized early response assessment criteria for evaluation of response to precision therapy.

Cost-effectiveness analysis of adjunct VSL#3 therapy versus standard medical therapy in pediatric ulcerative colitis.

PubMed

Park, K T; Perez, Felipe; Tsai, Raymond; Honkanen, Anita; Bass, Dorsey; Garber, Alan

2011-11-01

Inflammatory bowel diseases (IBDs) are costly chronic gastrointestinal diseases, with pediatric IBD representing increased costs per patient compared to adult disease. Health care expenditures for ulcerative colitis (UC) are >$2 billion annually. It is not clear whether the addition of VSL#3 to standard medical therapy in UC induction and maintenance of remission is a cost-effective strategy. We performed a systematic review of the literature and created a Markov model simulating a cohort of 10-year-old patients with severe UC, studying them until 100 years of age or death. We compared 2 strategies: standard medical therapy versus medical therapy + VSL#3. For both strategies, we assumed that patients progressed through escalating therapies--mesalamine, azathioprine, and infliximab--before receiving a colectomy + ileal pouch anal anastamosis (IPAA) if the 3 medical therapy options were exhausted. The primary outcome measure was the incremental cost-effectiveness ratio (ICER), defined as the difference of costs between strategies for each quality-adjusted life-year (QALY) gained. One-way sensitivity analyses were performed on variables to determine the key variables affecting cost-effectiveness. Standard medical care accrued a lifetime cost of $203,317 per patient, compared to $212,582 per patient for medical therapy + VSL#3. Lifetime QALYs gained was comparable for standard medical therapy and medical therapy + VSL#3 at 24.93 versus 25.05, respectively. Using the definition of ICER <50,000/QALY as a cost-effective intervention, medical therapy + VSL#3 produced an ICER of $79,910 per QALY gained, making this strategy cost-ineffective. Sensitivity analyses showed that 4 key parameters could affect the cost-effectiveness of the 2 strategies: cost of colectomy + IPAA, maintenance cost after surgery, probability of developing pouchitis after surgery, and the quality of life after a colectomy + IPAA. High surgical and postsurgical costs, a high probability of developing pouchitis, and a low quality of life after a colectomy + IPAA could make adjunct VSL#3 use a cost-effective strategy. Given present data, adjunct VSL#3 use for pediatric UC induction and maintenance of remission is not cost-effective, although several key parameters could make this strategy cost-effective. The quality of life after an IPAA is the single most important variable predicting whether this procedure benefits patients over escalating standard medical therapy.

Rationale for the tinnitus retraining therapy trial.

PubMed

Formby, Craig; Scherer, Roberta

2013-01-01

The Tinnitus Retraining Therapy Trial (TRTT) is a National Institutes of Health-sponsored, multi-centered, placebo-controlled, randomized trial evaluating the efficacy of tinnitus retraining therapy (TRT) and its component parts, directive counseling and sound therapy, as treatments for subjective debilitating tinnitus in the military. The TRTT will enroll 228 individuals at an allocation ratio of 1:1:1 to: (1) directive counseling and sound therapy using conventional sound generators; (2) directive counseling and placebo sound generators; or (3) standard of care as administered in the military. Study centers include a Study Chair's Office, a Data Coordinating Center, and six Military Clinical Centers with treatment and data collection standardized across all clinics. The primary outcome is change in Tinnitus Questionnaire (TQ) score assessed longitudinally at 3, 6, 12, and 18-month follow-up visits. Secondary outcomes include: Change in TQ sub-scales, Tinnitus Handicap Inventory, Tinnitus Functional Index, and TRT interview visual analog scale; audiometric and psychoacoustic measures; and change in quality of life. The TRTT will evaluate TRT efficacy by comparing TRT (directive counseling and conventional sound generators) with standard of care; directive counseling by comparing directive counseling plus placebo sound generators versus standard of care; and sound therapy by comparing conventional versus placebo sound generators. We hypothesize that full TRT will be more efficacious than standard of care, directive counseling and placebo sound generators more efficacious than standard of care, and conventional more efficacious than placebo sound generators in habituating the tinnitus awareness, annoyance, and impact on the study participant's life.

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

PubMed

Kumar, Neeraj; Goindi, Shishu

2014-09-10

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

Physiological closed-loop control in intelligent oxygen therapy: A review.

PubMed

Sanchez-Morillo, Daniel; Olaby, Osama; Fernandez-Granero, Miguel Angel; Leon-Jimenez, Antonio

2017-07-01

Oxygen therapy has become a standard care for the treatment of patients with chronic obstructive pulmonary disease and other hypoxemic chronic lung diseases. In current systems, manually continuous adjustment of O 2 flow rate is a time-consuming task, often unsuccessful, that requires experienced staff. The primary aim of this systematic review is to collate and report on the principles, algorithms and accuracy of autonomous physiological close-loop controlled oxygen devices as well to present recommendations for future research and studies in this area. A literature search was performed on medical database MEDLINE, engineering database IEEE-Xplore and wide-raging scientific databases Scopus and Web of Science. A narrative synthesis of the results was carried out. A summary of the findings of this review suggests that when compared to the conventional manual practice, the closed-loop controllers maintain higher saturation levels, spend less time below the target saturation, and save oxygen resources. Nonetheless, despite of their potential, autonomous oxygen therapy devices are scarce in real clinical applications. Robustness of control algorithms, fail-safe mechanisms, limited reliability of sensors, usability issues and the need for standardized evaluating methods of assessing risks can be among the reasons for this lack of matureness and need to be addressed before the wide spreading of a new generation of automatic oxygen devices. Copyright © 2017 Elsevier B.V. All rights reserved.

Juvenile idiopathic arthritis and athletic participation: are we adequately preparing for sports integration?

PubMed

Taxter, Alysha; Foss, Kim Barber; Melson, Paula; Ford, Kevin R; Shaffer, Michael; Myer, Gregory D

2012-09-01

Children with juvenile idiopathic arthritis (JIA) now have well-controlled disease due to improved therapies and management strategies. Children with JIA are more active than in the past and often participate in dynamic, high-loading sports. Standard measures of disease control include examination findings, laboratory values, and patient-directed surveys. However, these standards do not address the subtle deficits in biomechanics and neuromuscular control, which could place affected joints at higher risk for injury. Currently, there are limited evidence-based guidelines to structure conditioning recommendations as to the fitness and mechanics needed to provide safe integration into sports in this population; therefore, tools that objectively measure function with high accuracy and precision may be warranted. Previous work using 3-dimensional motion analysis demonstrated usefulness in guiding physical therapy treatment to correct these deficits. The use of a multidisciplinary team, including physical therapy, rheumatology, and sports medicine, is crucial for preparing these children to return to play. We suggest that the child transition into a sport preparatory-conditioning program to address any underlying deficits. A pediatric exercise specialist who is sensitive to the needs of this population can work with a physical therapist to then appropriately integrate the child safely into sport. Encouraging an active lifestyle is vital to the management of JIA and does not worsen the symptoms associated with childhood arthritis.

Adjuvant therapy in early-stage non-small cell lung cancer.

PubMed

Serke, Monika

2010-01-01

Evidence clearly supports adjuvant chemotherapy following resection in patients with stage II or III non-small cell lung cancer (NSCLC). Based on 3 landmark studies, adjuvant chemotherapy has become standard in completely resected NSCLC stage II and IIIA. Survival benefit from adjuvant chemotherapy is estimated to be between 3% and 15%, depending on stage. Treatment should include 4 cycles of platinum-based combination chemotherapy. There is uncertainty about chemotherapy prescription in those patients with resected stage IB NSCLC, as the risk of recurrence is lower in early NSCLC and the magnitude of benefit of adjuvant therapy is proportional to the risk of relapse according to stage. Postoperative radiotherapy (PORT) should not be used for stage I or II NSCLC, and remains controversial in resected stage IIIA (N2) disease. All positive adjuvant trials have utilized a cisplatin-based regimen, usually in combination with vinorelbine, and this should be considered the standard approach. Prognostic factors to select patients who will benefit from adjuvant therapy in general or from platinum-based chemotherapy are under discussion, but not yet established. In future we hope to optimize treatment convenience for the patients by using other combinations with the hope of better efficacy results. Work is currently under way to identify prognostic factors which in future may help to identify patients who are most likely to benefit from chemotherapy. Copyright 2010 S. Karger AG, Basel.

Targeted therapies in non-small cell lung cancer: a focus on ALK/ROS1 tyrosine kinase inhibitors.

PubMed

Sgambato, Assunta; Casaluce, Francesca; Maione, Paolo; Gridelli, Cesare

2018-01-01

Anaplastic lymphoma kinase (ALK) and ROS1 rearrangements define important molecular subgroups of advanced non-small cell lung cancer (NSCLC). The identification of these genetic driver alterations created new potential for highly active therapeutic interventions. After discovery of ALK rearrangements in NSCLC, it was recognized that these confer sensitivity to ALK inhibition. Areas covered: Crizotinib, the first-in-class ALK/ROS1/MET inhibitor, was initially approved as second-line treatment of ALK-positive advanced NSCLC but after this, it was firmly established as the standard first-line therapy for advanced ALK-positive NSCLC. After initial response to crizotinib, tumors inevitably relapse. Next-generation ALK inhibitors, more potent and brain-penetrable than crizotinib, may be effective in re-inducing remissions when cancers are still addicted to ALK. Ceritinib and alectinib are approved for metastatic ALK positive NSCLC patients, while brigatinib received granted accelerated approval by the United States Food and Drug Administration. Regarding ROS1 rearrangement, to date crizotinib is the only ALK-tyrosine kinase inhibitor receiving indication as treatment of ROS1 positive advanced NSCLC. Expert commentary: Although novel ALK-inhibitors are under clinical investigation compared to crizotinib as front-line treatment for ALK-positive NSCLC, nowadays the current standard first-line therapy for these patients is crizotinib. Further research will clarify the best management of ALK-positive NSCLC, above all who progress on first-line crizotinib.