Science.gov

Sample records for 90y-sirsphere treatment response

  1. Identifying predictors of treatment response.

    PubMed

    Yoder, Paul; Compton, Don

    2004-01-01

    This article provides a rationale for considering predictors of growth in a treatment group as inadequate to identifying predictors of treatment response. When we interpret predictors of growth in a treatment group as synonymous with predictors of treatment response, we implicitly attribute all of the treated children's growth to the treatment, an untenable assumption under most conditions. We also contend that the use of standard scores in predictors of growth studies does not allow us to differentiate growth from treatment, from growth from other factors. We present two research methodologies that are appropriate methods of identifying predictors of treatment response: (a) single-subject experimental logic utilized to identify the specific participants in which treatment responses (not just growth) were found, combined with follow-up group comparison logic to identify the characteristics on which responders and nonresponders differ, and (b) statistical interactions among child/family/context characteristics and randomly assigned group membership. Principles for selecting potential predictors of treatment response are provided.

  2. Pivotal Response Treatment: Case Reports.

    PubMed

    Ventola, Pamela; Friedman, Hannah; Oosting, Devon

    2015-01-01

    The current paper provides an overview of an evidence-based treatment, Pivotal Response Treatment (PRT), for autism spectrum disorder (ASD). The paper describes PRT principles and then illustrates the approach using two case reports. The children are preschool-aged children with high-functioning ASD. They were participating in a four-month clinical trial of PRT. At the start of treatment, they presented with significant social communication impairments, including a minimal understanding of reciprocity, limited play skills, and repetitive behaviors and speech. The paper outlines how behavioral treatment goals were identified and then how activities were designed, using principles of PRT, to target skill acquisition. Following the treatment course, both children made substantial and meaningful gains in social communication skill development.

  3. Non-response to osteoporosis treatment.

    PubMed

    Francis, Roger M

    2004-06-01

    There are now a number of effective treatments for osteoporosis, which increase bone mineral density (BMD) and decrease the risk of fractures. There is no clear consensus on the optimal method for assessing response to treatment in the individual patient. The goal of osteoporosis treatment is to prevent fractures after minimal trauma, but these are relatively uncommon events and cannot be totally avoided by the use of currently available therapies. Alternative methods of assessing response to treatment include serial measurement of BMD or the biochemical markers of bone turnover, but the observed changes may be misleading if they do not exceed the least significant change. The proportion of patients who fail to respond to osteoporosis treatments is difficult to quantify. Clinical trials show continuing bone loss in up to 15% of participants on hormone replacement therapy or bisphosphonates. Non-response to treatment is probably more common in clinical practice, but may be due to poor adherence to treatment recommendations. Other potential causes of an apparent failure to respond to treatment include the use of a weak antiresorptive agent, differences in bioavailability, low dietary calcium intake, vitamin D insufficiency and underlying causes of secondary osteoporosis. The management of patients who fail to respond to treatment includes confirmation that they are adhering to treatment and have an adequate dietary calcium intake and vitamin D status and excluding causes of secondary osteoporosis. Consideration should also be given to the addition of calcium and vitamin D supplementation and the use of alternative treatments for osteoporosis.

  4. Assessment of treatment response in tuberculosis.

    PubMed

    Rockwood, Neesha; du Bruyn, Elsa; Morris, Thomas; Wilkinson, Robert J

    2016-06-01

    Antibiotic treatment of tuberculosis has a duration of several months. There is significant variability of the host immune response and the pharmacokinetic-pharmacodynamic properties of Mycobacterium tuberculosis sub-populations at the site of disease. A limitation of sputum-based measures of treatment response may be sub-optimal detection and monitoring of Mycobacterium tuberculosis sub-populations. Potential biomarkers and surrogate endpoints should be benchmarked against hard clinical outcomes (failure/relapse/death) and may need tailoring to specific patient populations. Here, we assess the evidence supporting currently utilized and future potential host and pathogen-based models and biomarkers for monitoring treatment response in active and latent tuberculosis. Biomarkers for monitoring treatment response in extrapulmonary, pediatric and drug resistant tuberculosis are research priorities.

  5. Attraction, Discrepancy and Responses to Psychological Treatment.

    ERIC Educational Resources Information Center

    Patton, Michael J.

    The responses of a laboratory subject (S) to a counselor-accomplice and to the psychological treatment situation are examined by manipulating experimentally interpersonal attraction and communication discrepancy. Four treatment conditions were set up: (1) topic similarity and positive attraction for counselor, (2) topic discrepancy and positive…

  6. Heterogeneity of neural mechanisms of response to pivotal response treatment

    PubMed Central

    Ventola, Pamela; Yang, Daniel Y. J.; Friedman, Hannah E.; Oosting, Devon; Wolf, Julie; Sukhodolsky, Denis G.; Pelphrey, Kevin A.

    2016-01-01

    We investigated the mechanisms by which Pivotal Response Treatment (PRT) improves social communication in a case series of 10 preschool-aged children with Autism Spectrum Disorder (ASD). Functional magnetic resonance imaging (fMRI) identified brain responses during a biological motion perception task conducted prior to and following 16 weeks of PRT treatment. Overall, the neural systems supporting social perception in these 10 children were malleable through implementation of PRT; following treatment, neural responses were more similar to those of typically developing children (TD). However, at baseline, half of the children exhibited hypoactivation, relative to a group of TD children, in the right posterior superior temporal sulcus (pSTS), and half exhibited hyperactivation in this region. Strikingly, the groups exhibited differential neural responses to treatment: The five children who exhibited hypoactivation at baseline evidenced increased activation in components of the reward system including the ventral striatum and putamen. The five children who exhibited hyperactivation at baseline evidenced decreased activation in subcortical regions critical for regulating the flow of stimulation and conveying signals of salience to the cortex—the thalamus, amygdala, and hippocampus. Our results support further investigation into the differential effects of particular treatment strategies relative to specific neural targets. Identification of treatment strategies that address the patterns of neural vulnerability unique to each patient is consistent with the priority of creating individually tailored interventions customized to the behavioral and neural characteristics of a given person. PMID:25370452

  7. Daily Spiritual Experiences and Adolescent Treatment Response

    PubMed Central

    LEE, MATTHEW T.; VETA, PAIGE S.; JOHNSON, BYRON R.; PAGANO, MARIA E.

    2014-01-01

    The purpose of this study is to explore changes in belief orientation during treatment and the impact of increased daily spiritual experiences (DSE) on adolescent treatment response. One-hundred ninety-five adolescents court-referred to a 2-month residential treatment program were assessed at intake and discharge. Forty percent of youth who entered treatment as agnostic or atheist identified themselves as spiritual or religious at discharge. Increased DSE was associated with greater likelihood of abstinence, increased prosocial behaviors, and reduced narcissistic behaviors. Results indicate a shift in DSE that improves youth self-care and care for others that may inform intervention approaches for adolescents with addiction. PMID:25525291

  8. Treatment responses to tooth whitening in twins.

    PubMed

    Corby, Patricia M A; Biesbrock, Aaron; Gerlach, Robert; Corby, Andrea L; Moreira, Alexandre; Schork, Nicholas J; Bretz, Walter A

    2014-02-01

    The aim of this study was to determine heritability estimates of treatment responses to a 10% hydrogen peroxide strip-based whitening system in twins. Eighty-five twin pairs were randomly assigned to 10% hydrogen peroxide whitening strips or placebo strips without peroxide. Both twins (monozygotic or dizygotic) received the same treatment. Maxillary teeth were treated for 30 minutes twice daily for 7 days. Efficacy was measured objectively as L* (light-dark), a* (red-green), and b* (yellow-blue) color change from digital images at baseline (∆) and day 8. Heritability estimates for tooth whitening treatment responses for changes from day 8 to baseline were obtained using variance-component methodologies. Whitening treatment responses were highly heritable (h(2) = 71.0) for ∆b* and ∆a*(p < .0001), but not for ∆L* (h(2) = 27.0), which was essentially modulated by environmental factors. This study has demonstrated that both genetic and environmental factors significantly contributed to seven-day whitening treatment responses achieved with 10% hydrogen peroxide strips.

  9. Psychobiologic correlates of treatment response in schizophrenia.

    PubMed

    Lieberman, J A; Alvir, J M; Koreen, A; Geisler, S; Chakos, M; Sheitman, B; Woerner, M

    1996-03-01

    In studies conducted on largely treatment naive patients in their first episode of psychosis, we have found that treatment outcome is quite good and that most patients recover or at least achieve a substantial degree of symptom remission. However, over the course of their illness and in the context of subsequent psychotic episodes, they may experience some decrease in their treatment response from illness progression. In addition, the heterogeneity of treatment outcome is associated with specific clinical (gender, primary negative symptoms of the deficit state, duration of psychosis) and biological variables (pHVA, ventricular volume). It is unclear whether these variables represent aspects of discrete subtypes of schizophrenia or dimensional measures of pathology within the broad context of a unitary disease entity.

  10. Stream periphyton responses to mesocosm treatments of ...

    EPA Pesticide Factsheets

    A stream mesocosm experiment was designed to compare biotic responses among streams exposed to an equal excess specific conductivity target of 850 µS/cm relative to a control that was set for 200 µS/cm and three treatments comprised of different major ion contents. Each treatment and the control was replicated 4 times at the mesocosm scale (16 mesocosms total). The treatments were based on dosing the background mesocosm water, a continuous flow-through mixture of natural river water and reverse osmosis treated water, with stock salt solutions prepared from 1) a mixture of sodium chloride and calcium chloride (Na/Cl chloride), 2) sodium bicarbonate, and 3) magnesium sulfate. The realized average specific conductance over the first 28d of continuous dosing was 827, 829, and 847 µS/cm, for the chloride, bicarbonate, and sulfate based treatments, respectively, and did not differ significantly. The controls averaged 183 µS/cm. Here we focus on comparing stream periphyton communities across treatments based on measurements obtained from a Pulse-Amplitude Modulated (PAM) fluorometer. The fluorometer is used in situ and with built in algorithms distributes the total aerial algal biomass (µg/cm2) of the periphyton among cyanobacteria, diatoms, and green algae. A measurement is recorded in a matter of seconds and, therefore, many different locations can be measured with in each mesocosm at a high return frequency. Eight locations within each of the 1 m2 (0.3 m W x 3

  11. Preference for blocking or response redirection during stereotypy treatment.

    PubMed

    Giles, Aimee F; St Peter, Claire C; Pence, Sacha T; Gibson, Alexandra B

    2012-01-01

    Response redirection and response blocking reduce stereotypy maintained by automatic reinforcement. The current study evaluated the effects of redirection and response blocking on the stereotypic responding of three elementary-age children diagnosed with autism. During the treatment evaluation, redirection and response blocking were evaluated using an alternating treatment embedded in a reversal design. Both procedures resulted in comparably low levels of motor stereotypy. Following treatment evaluation, a concurrent chain was conducted to evaluate participant preference for redirection or response blocking. All three participants preferred redirection. Practitioners may wish to consider participant preference when developing and implementing treatments for stereotypy. Copyright © 2012 Elsevier Ltd. All rights reserved.

  12. Preference for Blocking or Response Redirection during Stereotypy Treatment

    ERIC Educational Resources Information Center

    Giles, Aimee F.; St. Peter, Claire C.; Pence, Sacha T.; Gibson, Alexandra B.

    2012-01-01

    Response redirection and response blocking reduce stereotypy maintained by automatic reinforcement. The current study evaluated the effects of redirection and response blocking on the stereotypic responding of three elementary-age children diagnosed with autism. During the treatment evaluation, redirection and response blocking were evaluated…

  13. Vegetation Response to Western Juniper Slash Treatments

    NASA Astrophysics Data System (ADS)

    O'Connor, Casey; Miller, Rick; Bates, Jonathan D.

    2013-09-01

    The expansion of piñon-juniper woodlands the past 100 years in the western United States has resulted in large scale efforts to kill trees and recover sagebrush steppe rangelands. It is important to evaluate vegetation recovery following woodland control to develop best management practices. In this study, we compared two fuel reduction treatments and a cut-and-leave (CUT) treatment used to control western juniper ( Juniperus occidentalis spp. occidentalis Hook.) of the northwestern United States. Treatments were; CUT, cut-and-broadcast burn (BURN), and cut-pile-and-burn the pile (PILE). A randomized complete block design was used with five replicates of each treatment located in a curl leaf mahogany ( Cercocarpus ledifolius Nutt. ex Torr. & A. Gray)/mountain big sagebrush ( Artemisia tridentata Nutt. spp. vaseyana (Rydb.) Beetle)/Idaho fescue ( Festuca idahoensis Elmer) association. In 2010, 4 years after tree control the cover of perennial grasses (PG) [Sandberg's bluegrass ( Poa secunda J. Pres) and large bunchgrasses] were about 4 and 5 % less, respectively, in the BURN (7.1 ± 0.6 %) than the PILE (11.4 ± 2.3 %) and CUT (12.4 ± 1.7 %) treatments ( P < 0.0015). In 2010, cover of invasive cheatgrass ( Bromus tectorum L.) was greater in the BURN (6.3 ± 1.0 %) and was 50 and 100 % greater than PILE and CUT treatments, respectively. However, the increase in perennial bunchgrass density and cover, despite cheatgrass in the BURN treatment, mean it unlikely that cheatgrass will persist as a major understory component. In the CUT treatment mahogany cover increased 12.5 % and density increased in from 172 ± 25 to 404 ± 123 trees/ha. Burning, killed most or all of the adult mahogany, and mahogany recovery consisted of 100 and 67 % seedlings in the PILE and BURN treatments, respectively. After treatment, juniper presence from untreated small trees (<1 m tall; PILE and CUT treatments) and seedling emergence (all treatments) represented 25-33 % of pre-treatment tree

  14. Novel Biomarker for Prognosis, Treatment Response

    Cancer.gov

    An NCI Cancer Currents blog about a study of a new type of cancer biomarker that measures the extent of chromosomal instability as a way to potentially predict patient prognosis and help guide cancer treatment choices.

  15. Mobile Emergency Response Water Treatment Technology Results

    EPA Science Inventory

    When natural disasters like hurricanes, floods and earthquakes occur, safe drinking water can be compromised, limited or unavailable. Under such situations, communities have emergency response plans. One of many options for providing safe drinking water during emergency situati...

  16. Mobile Emergency Response Water Treatment Technology Results

    EPA Science Inventory

    When natural disasters like hurricanes, floods and earthquakes occur, safe drinking water can be compromised, limited or unavailable. Under such situations, communities have emergency response plans. One of many options for providing safe drinking water during emergency situati...

  17. Rapid Response to Treatment for Binge Eating Disorder

    ERIC Educational Resources Information Center

    Grilo, Carlos M.; Masheb, Robin M.; Wilson, Terence G.

    2006-01-01

    The authors examined rapid response among 108 patients with binge eating disorder (BED) who were randomly assigned to 1 of 4 16-week treatments: fluoxetine, placebo, cognitive-behavioral therapy (CBT) plus fluoxetine, or CBT plus placebo. Rapid response, defined as 65% or greater reduction in binge eating by the 4th treatment week, was determined…

  18. Rapid Response to Treatment for Binge Eating Disorder

    ERIC Educational Resources Information Center

    Grilo, Carlos M.; Masheb, Robin M.; Wilson, Terence G.

    2006-01-01

    The authors examined rapid response among 108 patients with binge eating disorder (BED) who were randomly assigned to 1 of 4 16-week treatments: fluoxetine, placebo, cognitive-behavioral therapy (CBT) plus fluoxetine, or CBT plus placebo. Rapid response, defined as 65% or greater reduction in binge eating by the 4th treatment week, was determined…

  19. Baseline Brain Activity Predicts Response to Neuromodulatory Pain Treatment

    PubMed Central

    Jensen, Mark P.; Sherlin, Leslie H.; Fregni, Felipe; Gianas, Ann; Howe, Jon D.; Hakimian, Shahin

    2015-01-01

    Objectives The objective of this study was to examine the associations between baseline electroencephalogram (EEG)-assessed brain oscillations and subsequent response to four neuromodulatory treatments. Based on available research, we hypothesized that baseline theta oscillations would prospectively predict response to hypnotic analgesia. Analyses involving other oscillations and the other treatments (meditation, neurofeedback, and both active and sham transcranial direct current stimulation) were viewed as exploratory, given the lack of previous research examining brain oscillations as predictors of response to these other treatments. Design Randomized controlled study of single sessions of four neuromodulatory pain treatments and a control procedure. Methods Thirty individuals with spinal cord injury and chronic pain had their EEG recorded before each session of four active treatments (hypnosis, meditation, EEG biofeedback, transcranial direct current stimulation) and a control procedure (sham transcranial direct stimulation). Results As hypothesized, more presession theta power was associated with greater response to hypnotic analgesia. In exploratory analyses, we found that less baseline alpha power predicted pain reduction with meditation. Conclusions The findings support the idea that different patients respond to different pain treatments and that between-person treatment response differences are related to brain states as measured by EEG. The results have implications for the possibility of enhancing pain treatment response by either 1) better patient/treatment matching or 2) influencing brain activity before treatment is initiated in order to prepare patients to respond. Research is needed to replicate and confirm the findings in additional samples of individuals with chronic pain. PMID:25287554

  20. Baseline brain activity predicts response to neuromodulatory pain treatment.

    PubMed

    Jensen, Mark P; Sherlin, Leslie H; Fregni, Felipe; Gianas, Ann; Howe, Jon D; Hakimian, Shahin

    2014-12-01

    The objective of this study was to examine the associations between baseline electroencephalogram (EEG)-assessed brain oscillations and subsequent response to four neuromodulatory treatments. Based on available research, we hypothesized that baseline theta oscillations would prospectively predict response to hypnotic analgesia. Analyses involving other oscillations and the other treatments (meditation, neurofeedback, and both active and sham transcranial direct current stimulation) were viewed as exploratory, given the lack of previous research examining brain oscillations as predictors of response to these other treatments. Randomized controlled study of single sessions of four neuromodulatory pain treatments and a control procedure. Thirty individuals with spinal cord injury and chronic pain had their EEG recorded before each session of four active treatments (hypnosis, meditation, EEG biofeedback, transcranial direct current stimulation) and a control procedure (sham transcranial direct stimulation). As hypothesized, more presession theta power was associated with greater response to hypnotic analgesia. In exploratory analyses, we found that less baseline alpha power predicted pain reduction with meditation. The findings support the idea that different patients respond to different pain treatments and that between-person treatment response differences are related to brain states as measured by EEG. The results have implications for the possibility of enhancing pain treatment response by either 1) better patient/treatment matching or 2) influencing brain activity before treatment is initiated in order to prepare patients to respond. Research is needed to replicate and confirm the findings in additional samples of individuals with chronic pain. Wiley Periodicals, Inc.

  1. Legal and regulatory responses to innovative treatment.

    PubMed

    Chan, Tracey Evans

    2013-01-01

    Developments in medical technology, healthcare delivery, and commercial interests in medicine have increased both the potential for conflicts of interest on the part of physicians, and doubts over the sufficiency of patient autonomy as a justification for administering innovative therapy. The legal and regulatory treatment of innovative therapy is therefore an important question, on which there is a current lack of consensus on a number of issues. This paper discusses recent developments in Singapore and uses them as a springboard to flesh out basic regulatory issues that arise from the deployment of innovative treatment: the distinction between innovative treatment and clinical research, the adequacy of the current post hoc scrutiny of innovative therapy under existing legal principles and the need for further specialised regulatory oversight.

  2. Natural regeneration response to initial treatments

    Treesearch

    G. E. Gruell; W. C. Schmidt; S. F. Arno; W. J. Reich; James Menakis

    1999-01-01

    During the 1907 to 1911 harvest, logs were transported to landings by means of log chutes, horse skidding, and steam donkey yarding. Slash was disposed of by piling and burning, which the purchaser considered to be an unnecessary practice (Koch 1998). Usually this type of logging and postlogging treatment results in relatively light site disturbance, and the photo...

  3. Automated Demand Response Opportunities in Wastewater Treatment Facilities

    SciTech Connect

    Thompson, Lisa; Song, Katherine; Lekov, Alex; McKane, Aimee

    2008-11-19

    Wastewater treatment is an energy intensive process which, together with water treatment, comprises about three percent of U.S. annual energy use. Yet, since wastewater treatment facilities are often peripheral to major electricity-using industries, they are frequently an overlooked area for automated demand response opportunities. Demand response is a set of actions taken to reduce electric loads when contingencies, such as emergencies or congestion, occur that threaten supply-demand balance, and/or market conditions occur that raise electric supply costs. Demand response programs are designed to improve the reliability of the electric grid and to lower the use of electricity during peak times to reduce the total system costs. Open automated demand response is a set of continuous, open communication signals and systems provided over the Internet to allow facilities to automate their demand response activities without the need for manual actions. Automated demand response strategies can be implemented as an enhanced use of upgraded equipment and facility control strategies installed as energy efficiency measures. Conversely, installation of controls to support automated demand response may result in improved energy efficiency through real-time access to operational data. This paper argues that the implementation of energy efficiency opportunities in wastewater treatment facilities creates a base for achieving successful demand reductions. This paper characterizes energy use and the state of demand response readiness in wastewater treatment facilities and outlines automated demand response opportunities.

  4. Prediction of treatment response to rivastigmine in Alzheimer's dementia

    PubMed Central

    Adler, G; Brassen, S; Chwalek, K; Dieter, B; Teufel, M

    2004-01-01

    Methods: A neuropsychological examination and a quantitative EEG study were done in 20 patients with Alzheimer's dementia before initiating treatment with rivastigmine. After one week of treatment a second EEG examination was done. Therapeutic efficacy was determined six months after treatment initiation. Treatment response was defined as improvement in short term memory after six months of rivastigmine treatment. Results: For the group of patients as a whole, there was a significant improvement in short term memory and orientation during rivastigmine treatment. The mini-mental state score improved from 20.2 to 21.7 (NS). In the EEG, theta power decreased significantly after one week of treatment. Treatment responders had a greater decrease in theta power after one week of treatment and a better short term memory at baseline than non-responders. Decrease in theta power during rivastigmine treatment and baseline short term memory were good predictors of treatment response. Conclusions: Generally available neuropsychological and EEG data may be useful for predicting response to rivastigmine in patients with Alzheimer's disease. PMID:14742608

  5. Predictors of Treatment Response in Pediatric Obsessive-Compulsive Disorder

    ERIC Educational Resources Information Center

    Ginsburg, Golda S.; Kingery, Julie Newman; Drake, Kelly L.; Grados, Marco A.

    2008-01-01

    The study examines predictors of treatment response in pediatric obsessive-compulsive disorder, which is a severe mental illness causing distress and impaired functioning. Summarized findings of psychosocial factors and medication interventions are presented.

  6. Predictors of Treatment Response in Pediatric Obsessive-Compulsive Disorder

    ERIC Educational Resources Information Center

    Ginsburg, Golda S.; Kingery, Julie Newman; Drake, Kelly L.; Grados, Marco A.

    2008-01-01

    The study examines predictors of treatment response in pediatric obsessive-compulsive disorder, which is a severe mental illness causing distress and impaired functioning. Summarized findings of psychosocial factors and medication interventions are presented.

  7. A system for identifying and investigating unexpected response to treatment.

    PubMed

    Ozery-Flato, Michal; Ein-Dor, Liat; Neuvirth, Hani; Parush, Naama; Kohn, Martin S; Hu, Jianying; Aharonov, Ranit

    2015-01-01

    The availability of electronic health records creates fertile ground for developing computational models for various medical conditions. Using machine learning, we can detect patients with unexpected responses to treatment and provide statistical testing and visualization tools to help further analysis. The new system was developed to help researchers uncover new features associated with reduced response to treatment, and to aid physicians in identifying patients that are not responding to treatment as expected and hence deserve more attention. The solution computes a statistical score for the deviation of a given patient's response from responses observed individuals with similar characteristics and medication regimens. Statistical tests are then applied to identify clinical features that correlate with cohorts of patients showing deviant responses. The results provide comprehensive visualizations, both at the cohort and the individual patient levels. We demonstrate the utility of this system in a population of diabetic patients.

  8. Implicit Learning Abilities Predict Treatment Response in Autism Spectrum Disorders

    DTIC Science & Technology

    2015-09-01

    2 AWARD NUMBER: W81XWH-14-1-0261 TITLE: Implicit Learning Abilities Predict Treatment Response in Autism Spectrum Disorders PRINCIPAL...Treatment Response in Autism Spectrum Disorders 5b. GRANT NUMBER W81XWH-14-1-0261 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER...for Autism Spectrum Disorder (ASD), but almost half of the children do not make significant gains. Implicit learning skills are integral to

  9. FDG-PET/CT based response-adapted treatment

    PubMed Central

    Vriens, Dennis; Arens, Anne I.J.; Hutchings, Martin; Oyen, Wim J.G.

    2012-01-01

    Abstract It has been shown that [18F]fluorodeoxyglucose (FDG)-positron emission tomography (PET) provides robust and reproducible data for early metabolic response assessment in various malignancies. This led to the initiation of several prospective multicenter trials in malignant lymphoma and adenocarcinoma of the esophagogastric junction, in order to investigate whether the use of PET-guided treatment individualization results in a survival benefit. In Hodgkin lymphoma and aggressive non-Hodgkin lymphoma, several trials are ongoing. Some studies aim to investigate the use of PET in early identification of metabolic non-responders in order to intensify treatment to improve survival. Other studies aim at reducing toxicity without adversely affecting cure rates by safely de-escalating therapy in metabolic responders. In solid tumors the first PET response-adjusted treatment trials have been realized in adenocarcinoma of the esophagogastric junction. These trials showed that patients with an early metabolic response to neoadjuvant chemotherapy benefit from this treatment, whereas metabolic non-responders should switch early to surgery, thus reducing the risk of tumor progression during chemotherapy and the risk of toxic death. The trials provide a model for designing response-guided treatment algorithms in other malignancies. PET-guided treatment algorithms are the promise of the near future; the choice of therapy, its intensity, and its duration will become better adjusted to the biology of the individual patient. Today’s major challenge is to investigate the impact on patient outcome of personalized response-adapted treatment concepts. PMID:23023063

  10. Choosing treatment for depression in older adults and evaluating response.

    PubMed

    Arean, Patricia A; Niu, Grace

    2014-08-01

    An update is provided on the current information regarding late life depression with regard to assessment, clinical implications, and treatment recommendations. Several treatments are considered evidence-based, but when deployed into field trials, the efficacy of these treatments falls short. It is thought that the lower impact in community trials is due in large part to patient, clinical, environmental, socio-economic, and cognitive correlates that influence treatment response. The aim is to assist providers in making decisions about what type of treatment to recommend based on a sound assessment of these clinical correlates. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. Pivotal Response Treatments for Autism: Communication, Social, and Academic Development

    ERIC Educational Resources Information Center

    Koegel, Robert L.; Kern Koegel, Lynn

    2006-01-01

    Recognized as one of the top state-of-the-art treatments for autism in the United States, the innovative Pivotal Response Treatment uses natural learning opportunities to target and modify key behaviors in children with autism, leading to widespread positive effects on communication, behavior, and social skills. The product of 20 years of…

  12. Initial response of understory vegetation to three alternative thinning treatments

    Treesearch

    Liane R. Davis; Klaus J. Puettmann

    2009-01-01

    This study compares initial understory vegetation response among three thinning treatments and a control in 30 - to 50-year-old even-aged Pseudotsuga menziesii (Mirbel) Franco (Douglas-fir) stands. It was conducted on four sites on the western slope of the central Oregon Cascades. Treatments included a control (no thinning), a light thinning, and...

  13. Pivotal Response Treatments for Autism: Communication, Social, and Academic Development

    ERIC Educational Resources Information Center

    Koegel, Robert L.; Kern Koegel, Lynn

    2006-01-01

    Recognized as one of the top state-of-the-art treatments for autism in the United States, the innovative Pivotal Response Treatment uses natural learning opportunities to target and modify key behaviors in children with autism, leading to widespread positive effects on communication, behavior, and social skills. The product of 20 years of…

  14. Examination of Studies Targeting Social Skills with Pivotal Response Treatment

    ERIC Educational Resources Information Center

    Bozkus Genc, Gulden; Vuran, Sezgin

    2013-01-01

    In early education, especially in effective teaching to children with autism spectrum disorders, the teaching methods which are applicable in natural settings like pivotal response treatment (PRT) are commonly used. It is one of the naturalistic intervention models aiming to facilitate the stimulant-response generalization, decrease the dependency…

  15. The heterogeneity of antipsychotic response in the treatment of schizophrenia

    PubMed Central

    Case, M.; Stauffer, V. L.; Ascher-Svanum, H.; Conley, R.; Kapur, S.; Kane, J. M.; Kollack-Walker, S.; Jacob, J.; Kinon, B. J.

    2011-01-01

    Background Schizophrenia is a heterogeneous disorder in terms of patient response to antipsychotic treatment. Understanding the heterogeneity of treatment response may help to guide treatment decisions. This study was undertaken to capture inherent patterns of response to antipsychotic treatment in patients with schizophrenia, characterize the subgroups of patients with similar courses of response, and examine illness characteristics at baseline as possible predictors of response. Method Growth mixture modeling (GMM) was applied to data from a randomized, double-blind, 12-week study of 628 patients with schizophrenia or schizo-affective disorder treated with risperidone or olanzapine. Results Four distinct response trajectories based on Positive and Negative Syndrome Scale (PANSS) total score over 12 weeks were identified: Class 1 (420 patients, 80.6%) with moderate average baseline PANSS total score showing gradual symptom improvement; Class 2 (65 patients, 12.5%) showing rapid symptom improvement; Class 3 (24 patients, 4.6%) with high average baseline PANSS total score showing gradual symptom improvement; and Class 4 (12 patients, 2.3%) showing unsustained symptom improvement. Latent class membership of early responders (ER) and early non-responders (ENR) was determined based on 20% symptom improvement criteria at 2 weeks and ultimate responders (UR) and ultimate non-responders (UNR) based on 40% symptom improvement criteria at 12 weeks. Baseline factors with potential influence on latent class membership were identified. Conclusions This study identified four distinct treatment response patterns with predominant representation of responders or non-responders to treatment in these classes. This heterogeneity may represent discrete endophenotypes of response to treatment with different etiologic underpinnings. PMID:20925971

  16. Patterns of Response After Preoperative Treatment in Gastric Cancer

    SciTech Connect

    Diaz-Gonzalez, Juan A.; Rodriguez, Javier; Hernandez-Lizoain, Jose L.; Ciervide, Raquel; Gaztanaga, Miren; San Miguel, Inigo; Arbea, Leire; Aristu, J. Javier; Chopitea, Ana; Martinez-Regueira, Fernando; Valenti, Victor; Garcia-Foncillas, Jesus; Martinez-Monge, Rafael; Sola, Jesus J.

    2011-07-01

    Purpose: To analyze the rate of pathologic response in patients with locally advanced gastric cancer treated with preoperative chemotherapy with and without chemoradiation at our institution. Methods and Materials: From 2000 to 2007 patients were retrospectively identified who received preoperative treatment for gastric cancer (cT3-4/ N+) with induction chemotherapy (Ch) or with Ch followed by concurrent chemoradiotherapy (45 Gy in 5 weeks) (ChRT). Surgery was planned 4-6 weeks after the completion of neoadjuvant treatment. Pathologic assessment was used to investigate the patterns of pathologic response after neoadjuvant treatment. Results: Sixty-one patients were analyzed. Of 61 patients, 58 (95%) underwent surgery. The R0 resection rate was 87%. Pathologic complete response was achieved in 12% of the patients. A major pathologic response (<10% of residual tumor) was observed in 53% of patients, and T downstaging was observed in 75%. Median follow-up was 38.7 months. Median disease-free survival (DFS) was 36.5 months. The only patient-, tumor-, and treatment-related factor associated with pathologic response was the use of preoperative ChRT. Patients achieving major pathologic response had a 3-year actuarial DFS rate of 63%. Conclusions: The patterns of pathologic response after preoperative ChRT suggest encouraging intervals of DFS. Such a strategy may be of interest to be explored in gastric cancer.

  17. Soft-Tissue Abnormalities Associated with Treatment-Resistant and Treatment-Responsive Clubfoot

    PubMed Central

    Moon, Daniel K.; Gurnett, Christina A.; Aferol, Hyuliya; Siegel, Marilyn J.; Commean, Paul K.; Dobbs, Matthew B.

    2014-01-01

    Background: Clubfoot treatment commonly fails and often results in impaired quality of life. An understanding of the soft-tissue abnormalities associated with both treatment-responsive and treatment-resistant clubfoot is important to improving the diagnosis of clubfoot, the prognosis for patients, and treatment. Methods: Twenty patients with clubfoot treated with the Ponseti method were recruited for magnetic resonance imaging (MRI) of their lower extremities. Among these were seven patients (six unilateral cases) with treatment-responsive clubfoot and thirteen patients (five unilateral cases) with treatment-resistant clubfoot. Demographic information and physical examination findings were recorded. A descriptive analysis of the soft-tissue abnormalities was performed for both patient cohorts. For the patients with unilateral clubfoot, we calculated the percentage difference in cross-sectional area between the affected limb and the unaffected limb in terms of muscle, subcutaneous fat, intracompartment fat, and total area. With use of the Wilcoxon signed-rank test, we compared inter-leg differences in cross-sectional areas and the intracompartment adiposity index (IAI) between treatment-responsive and treatment-resistant groups. The IAI characterizes the cross-sectional area of fat within a muscle compartment. Results: Extensive soft-tissue abnormalities were more present in patients with treatment-resistant clubfoot than in patients with treatment-responsive clubfoot. Treatment-resistant clubfoot abnormalities included excess epimysial fat and intramuscular fat replacement as well as unique patterns of hypoplasia in specific muscle groups that were present within a subset of patients. Among the unilateral cases, treatment-resistant clubfoot was associated with a significantly greater difference in muscle area between the affected and unaffected limb (−47.8%) compared with treatment-responsive clubfoot (−26.6%) (p = 0.02), a significantly greater difference in

  18. Modulation of the host response in the treatment of periodontitis.

    PubMed

    Golub, L M; Ryan, M E; Williams, R C

    1998-10-01

    Periodontitis has two distinct but interconnected etiologic components: periodontopathic bacteria adjacent to the periodontal tissues, and host-mediated connective tissue-destructive responses to the specific causative bacteria and their metabolic products. Although past and existing therapies have focused primarily on the causative microbial challenge, the host component of periodontal destruction has recently been intensely studied. New treatment strategies that focus on attenuating destructive host responses are emerging. Host modulatory agents, when used adjunctively, may enhance clinical therapeutic responses and make these responses more predictable in the susceptible host. The ongoing development of safe, effective pharmacotherapies that specifically target host response mechanisms, and the introduction of such pharmacotherapies as adjuncts to traditional, antimicrobial interventions may represent a new, integrated approach in the long-term treatment and management of this chronic disease.

  19. Is the Ultimate Treatment Response Predictable with Early Response in Major Depressive Episode?

    PubMed Central

    ÇİFTÇİ, Aslı; ULAŞ, Halis; TOPUZOĞLU, Ahmet; TUNCA, Zeliha

    2016-01-01

    Introduction New evidence suggests that the efficacy of antidepressants occurs within the first weeks of treatment and this early response predicts the later response. The purpose of the present study was to investigate if the partial response in the first week predicts the response at the end of treatment in patients with major depressive disorder who are treated with either antidepressant medication or electroconvulsive therapy. Methods Inpatients from Dokuz Eylül University Hospital with a major depressive episode, treated with antidepressant medication (n=52) or electroconvulsive therapy (ECT) (n=48), were recruited for the study. The data were retrospectively collected to decide whether a 25% decrease in the Hamilton Depression Rating Scale (HDRS) score at the first week of treatment predicts a 50% decrease at the third week using validity analysis. In addition, the effects of socio-demographic and clinical variables on the treatment response were assessed. Results A 25% decrease in the HDRS score in the first week of treatment predicted a 50% decrease in the HDRS score in the third week with a 78.3% positive predictive value, 62.1% negative predictive value, 62.1% sensitivity, and 78.3% specificity for antidepressant medications and an 88% positive predictive value, 52.2% negative predictive value, 66.7% sensitivity, and 80% specificity for ECT. The number of previous hospitalizations, comorbid medical illnesses, number of depressive episodes, duration of illness, and duration of the current episode were related to the treatment response. Conclusion Treatment response in the first week predicted the response in the third week with a high specificity and a high positive predictive value. Close monitoring of the response from the first week of treatment may thus help the clinician to predict the subsequent response. PMID:28373802

  20. Imaging in evaluation of response to neoadjuvant breast cancer treatment

    PubMed Central

    Ollivier, L; Balu-Maestro, C; Leclère, J

    2005-01-01

    The role of imaging for patients treated with neoadjuvant therapy for breast cancer is not only to evaluate the therapeutic response in terms of tumour shrinkage, but also to predict the histological response to chemotherapy, which is correlated to survival. Surgery and histopathological analysis after neoadjuvant therapy allow for an objective assessment of the accuracy of imaging techniques in evaluating response. The aim of this study is to compare the value of the different conventional and functional imaging techniques for determining response to neoadjuvant chemotherapy in breast cancer treatment. PMID:16154816

  1. Defining Treatment Response in Trichotillomania: A Signal Detection Analysis

    PubMed Central

    Houghton, David C.; Capriotti, Matthew R.; De Nadai, Alessandro S.; Compton, Scott N.; Twohig, Michael P.; Neal-Barnett, Angela M.; Saunders, Stephen M.; Franklin, Martin E.; Woods, Douglas W.

    2015-01-01

    The Massachusetts General Hospital Hairpulling Scale (MGH-HPS) and the NIMH Trichotillomania Severity Scale (NIMH-TSS) are two widely used measures of trichotillomania severity. Despite their popular use, currently no empirically-supported guidelines exist to determine the degrees of change on these scales that best indicate treatment response. Determination of such criteria could aid in clinical decision-making by defining clinically significant treatment response/recovery and producing accurate power analyses for use in clinical trials research. Adults with trichotillomania (N = 69) participated in a randomized controlled trial of psychotherapy and were assessed before and after treatment. Response status was measured via the Clinical Global Impressions-Improvement Scale, and remission status was measured via the Clinical Global Impressions-Severity Scale. For treatment response, a 45% reduction or 7-point raw score change on the MGH-HPS was the best indicator of clinically significant treatment response, and on the NIMH-TSS, a 30–40% reduction or 6-point raw score difference was most effective cutoff. For disorder remission, a 55–60% reduction or 7-point raw score change on the MGH-HPS was the best predictor, and on the NIMH-TSS, a 65% reduction or 6-point raw score change was the best indicator of disorder remission. Implications of these findings are discussed. PMID:26422605

  2. Antipsychotic induced metabolic changes & treatment response: a prospective study.

    PubMed

    Sharma, Eesha; Venkatasubramanian, Ganesan; Varambally, Shivarama; Sivakumar, Palanimuthu T; Subbakrishna, Doddaballapur K; Gangadhar, Bangalore N

    2014-10-01

    Metabolic side effects of antipsychotics contribute to morbidity and non-compliance in treatment of psychosis. Multiple studies suggest that metabolic side effects correlate with response to antipsychotic treatment. However, few studies have systematically looked at this. We conducted an exploratory, naturalistic, prospective, trans-diagnostic study to examine this association. 100 patients with psychosis, initiated on antipsychotic treatment alone, were assessed on Brief Psychiatric Rating Scale (BPRS), visual analog scale for appetite, anthropometric measurements (weight, waist circumference, body mass index), and fasting serum lipid and glucose profiles at baseline, 2-4 weeks (n=71) and 8-12 weeks (n=39). Subjects who dropped out at first/second follow-ups did not differ from those who followed-up, in age, sex, illness duration and BPRS scores. On forward stepwise multiple linear regression analysis, early (2-4 weeks) increase in appetite and triglyceride levels (R(2)=0.257; p=0.003) together predicted 26% variance in treatment response (BPRS score reduction) at first follow-up. At second follow-up 16% of variance in treatment response was predicted by early (2-4 weeks) increase in triglyceride levels (R(2)=0.169; p=0.009). Early appetite and triglyceride changes predicted antipsychotic treatment response. Involvement of dopaminergic, serotonergic and histaminergic neural pathways could explain the association between appetite and treatment response. Insulin signaling pathways have been implicated in lipid changes with antipsychotics. Study findings suggest metabolic side effects may be early predictors of antipsychotic response. These findings warrant further examination to elucidate the interaction between metabolic pathways and psychotic illnesses, and possibly mechanism of action of antipsychotics beyond dopamine blockade. Copyright © 2014 Elsevier B.V. All rights reserved.

  3. The Impact of PTSD Treatment on the Cortisol Awakening Response

    PubMed Central

    Pacella, Maria L.; Feeny, Norah; Zoellner, Lori; Delahanty, Douglas L.

    2015-01-01

    Background Posttraumatic stress disorder (PTSD) is associated with abnormal functioning of the hypothalamic-pituitary-adrenal (HPA) axis; however, limited research has examined whether cortisol levels change following successful PTSD treatment. The current study examined the impact of successful PTSD treatment on the cortisol awakening response (CAR). Method Twenty-nine adults participating in a treatment trial for chronic PTSD provided saliva samples (upon waking, and 30, 45, and 60-min post-waking) before and after receiving either prolonged exposure therapy or sertraline. PTSD responder status (i.e., loss or retention of a PTSD diagnosis) served as the predictor variable. Outcome measures included area under the curve with respect to ground and increase, reflecting total cortisol output and HPA axis reactivity, respectively. Results A series of hierarchical regressions revealed no significant main effects of PTSD responder status for either CAR outcome. However, a significant gender by treatment response interaction for cortisol reactivity revealed that female treatment non-responders displayed higher cortisol reactivity following treatment than female responders, whereas cortisol reactivity did not change pre- to post-treatment for male responders. Findings remained after controlling for age, trauma history, baseline medication status, baseline PTSD, and baseline depressive symptoms. Conclusion Loss of a PTSD diagnosis may contribute to decreased cortisol reactivity in females. Neuroendocrine changes following treatment may emerge only for specific subgroups, highlighting the importance of exploring treatment moderators. PMID:25327949

  4. Is treatment-resistant schizophrenia categorically distinct from treatment-responsive schizophrenia? a systematic review.

    PubMed

    Gillespie, Amy L; Samanaite, Ruta; Mill, Jonathan; Egerton, Alice; MacCabe, James H

    2017-01-13

    Schizophrenia is a highly heterogeneous disorder, and around a third of patients are treatment-resistant. The only evidence-based treatment for these patients is clozapine, an atypical antipsychotic with relatively weak dopamine antagonism. It is plausible that varying degrees of response to antipsychotics reflect categorically distinct illness subtypes, which would have significant implications for research and clinical practice. If these subtypes could be distinguished at illness onset, this could represent a first step towards personalised medicine in psychiatry. This systematic review investigates whether current evidence supports conceptualising treatment-resistant and treatment-responsive schizophrenoa as categorically distinct subtypes. A systematic literature search was conducted, using PubMed, EMBASE, PsycInfo, CINAHL and OpenGrey databases, to identify all studies which compared treatment-resistant schizophrenia (defined as either a lack of response to two antipsychotic trials or clozapine prescription) to treatment-responsive schizophrenia (defined as known response to non-clozapine antipsychotics). Nineteen studies of moderate quality met inclusion criteria. The most robust findings indicate that treatment-resistant patients show glutamatergic abnormalities, a lack of dopaminergic abnormalities, and significant decreases in grey matter compared to treatment-responsive patients. Treatment-resistant patients were also reported to have higher familial loading; however, no individual gene-association study reported their findings surviving correction for multiple comparisons. Tentative evidence supports conceptualising treatment-resistant schizophrenia as a categorically different illness subtype to treatment-responsive schizophrenia. However, research is limited and confirmation will require replication and rigorously controlled studies with large sample sizes and prospective study designs.

  5. Effect of inadequate response to treatment in patients with depression.

    PubMed

    Knoth, Russell L; Bolge, Susan C; Kim, Edward; Tran, Quynh-Van

    2010-08-01

    To assess the effects of inadequate response to antidepressant treatment on healthcare resource utilization and on work productivity in patients diagnosed as having major depressive disorder (MDD). This study used data from the 2006 US National Health and Wellness Survey, a cross-sectional survey of adults 18 years and older. Patients who self-reported a confirmed diagnosis of depression and were currently taking antidepressant medication were included in the analyses. Adequacy of antidepressant treatment response was determined from responses to the mental health domain of the 8-Item Short Form Health Survey (SF-8). Logistic regression analyses adjusted for demographics, comorbidity, and component scores on the SF-8 were used to determine the associations between inadequacy of treatment response and health outcomes. Of 5988 patients who met the inclusion criteria for the study, 30.9% were classified as antidepressant treatment responders, 31.2% were partial responders, and 37.9% were nonresponders. Partial response and nonresponse to treatment were associated with greater likelihood of emergency department utilization (odds ratios [ORs], 1.26 and 1.54, respectively; P <.01 for both) and hospitalization (OR, 1.23; P = .05 and OR, 1.39; P <.01, respectively). Similarly, partial response and nonresponse were associated with lower likelihood of current employment (OR, 0.83; P = .01 and OR, 0.63; P <.01, respectively) and with greater likelihood of work productivity loss among the employed (ORs, 1.42 and 1.99, respectively; P <.01 for both). Patients with MDD who failed to respond to antidepressant treatment as evidenced by poor self-reported mental health status used more healthcare resources, were less likely to be employed, and had more work productivity loss than those who responded to antidepressant therapy.

  6. Opportunities for Automated Demand Response in California Wastewater Treatment Facilities

    SciTech Connect

    Aghajanzadeh, Arian; Wray, Craig; McKane, Aimee

    2015-08-30

    Previous research over a period of six years has identified wastewater treatment facilities as good candidates for demand response (DR), automated demand response (Auto-­DR), and Energy Efficiency (EE) measures. This report summarizes that work, including the characteristics of wastewater treatment facilities, the nature of the wastewater stream, energy used and demand, as well as details of the wastewater treatment process. It also discusses control systems and automated demand response opportunities. Furthermore, this report summarizes the DR potential of three wastewater treatment facilities. In particular, Lawrence Berkeley National Laboratory (LBNL) has collected data at these facilities from control systems, submetered process equipment, utility electricity demand records, and governmental weather stations. The collected data were then used to generate a summary of wastewater power demand, factors affecting that demand, and demand response capabilities. These case studies show that facilities that have implemented energy efficiency measures and that have centralized control systems are well suited to shed or shift electrical loads in response to financial incentives, utility bill savings, and/or opportunities to enhance reliability of service. In summary, municipal wastewater treatment energy demand in California is large, and energy-­intensive equipment offers significant potential for automated demand response. In particular, large load reductions were achieved by targeting effluent pumps and centrifuges. One of the limiting factors to implementing demand response is the reaction of effluent turbidity to reduced aeration at an earlier stage of the process. Another limiting factor is that cogeneration capabilities of municipal facilities, including existing power purchase agreements and utility receptiveness to purchasing electricity from cogeneration facilities, limit a facility’s potential to participate in other DR activities.

  7. Expectation, the placebo effect and the response to treatment.

    PubMed

    Brown, Walter A

    2015-05-01

    What we believe we will experience from a treatment--our expectation--has a substantial impact on what we actually experience. Expectation has been established as a key process behind the placebo effect. Studies in both laboratory and clinical settings consistently show that when people ingest a pharmacologically inert substance (placebo) but believe that it is an active substance, they experience both the subjective sensations and physiologic effects expected from that active substance. Expectation has an important place in the response to "real" treatment as well. This paper provides an overview of the data which point to the role of expectation in both the placebo effect and the response to treatment. These data suggest that clinicians might enhance the benefit of all treatments by promoting patients' positive expectations.

  8. Predictors of response to neuroleptic treatment in schizophrenia.

    PubMed

    Stern, R G; Kahn, R S; Davidson, M

    1993-06-01

    Baseline symptom severity, early reduction in symptom severity, initial subjective response to neuroleptic treatment, the degree of brain atrophy, and early changes in pHVA levels appear to predict treatment outcome in schizophrenic patients. Computerized EEG results, neuropsychological and neurophysiologic tests, and baseline pHVA concentrations require further examination. Only a limited proportion of variance in treatment response, however, could be explained by either of the nine predictors alone or combined. Therefore, further research is necessary to discover yet unidentified determinants of treatment response. Future studies should test the validity and reliability of these five promising predictors in large groups of male and female patients, employ high standards for assessment reliability of clinical parameters, and use absolute rating scores on psychopathology as well as functional scales for the definition of good and poor treatment response. Furthermore, the statistical approach for data analysis should take in consideration the need for appropriate corrections when multiple correlations are performed and should test the extent to which these predictors are interdependent.

  9. A new paradigm for the prediction of antidepressant treatment response

    PubMed Central

    Leuchter, Andrew F.; Cook, Ian A.; Hunter, Aimee M.; Korb, Alexander S.

    2009-01-01

    Current treatment of Major Depressive Disorder utilizes a trial-and-error sequential treatment strategy that results in delays in achieving response and remission for a majority of patients. Protracted ineffective treatment prolongs patient suffering and increases health care costs. In addition, long and unsuccessful antidepressant trials may diminish patient expectations, reinforce negative cognitions, and condition patients not to respond during subsequent antidepressant trials, thus contributing to further treatment resistance. For these reasons, it is critical to identify reliable predictors of antidepressant treatment response that can be used to shorten or eliminate lengthy and ineffective trials. Research on possible endophenotypic as well as genomic predictors has not yet yielded reliable predictors. The most reliable predictors identified thus far are symptomatic and physiologic characteristics of patients that emerge early in the course of treatment. We propose here the term “response endophenotypes” (REs) to describe this class of predictors, defined as latent measurable symptomatic or neurobiologie responses of individual patients that emerge early in the course of treatment, and which carry strong predictive power for individual patient outcomes. Use of REs constitutes a new paradigm in which medication treatment trials that are likely to be ineffective could be stopped within 1 to 2 weeks and other medication more likely to be effective could be started. Data presented here suggest that early changes in symptoms, quantitative electroencephalography, and gene expression could be used to construct effective REs. We posit that this new paradigm could lead to earlier recovery from depressive illness and ultimately produce profound health and economic benefits. PMID:20135901

  10. Treatment-Resistant Schizophrenia Patients Show Elevated Anterior Cingulate Cortex Glutamate Compared to Treatment-Responsive.

    PubMed

    Mouchlianitis, Elias; Bloomfield, Michael A P; Law, Vincent; Beck, Katherine; Selvaraj, Sudhakar; Rasquinha, Naresh; Waldman, Adam; Turkheimer, Federico E; Egerton, Alice; Stone, James; Howes, Oliver D

    2016-05-01

    Resistance to antipsychotic treatment is a significant clinical problem in patients with schizophrenia with approximately 1 in 3 showing limited or no response to repeated treatments with antipsychotic medication. The neurobiological basis for treatment resistance is unknown but recent evidence implicates glutamatergic function in the anterior cingulate cortex. We examined glutamate levels of chronically ill treatment-resistant patients directly compared to treatment-responsive patients. We acquired proton magnetic resonance spectroscopy (1H-MRS) at 3 Tesla from 21 treatment-resistant and 20 treatment-responsive patients. All participants had a DSM-IV diagnosis of schizophrenia. Treatment-resistant patients were classified using the modified Kane criteria. The groups were matched for age, sex, smoking status, and illness duration. Glutamate to creatine ratio levels were higher in treatment-resistant patients (Mean [SD] = 1.57 [0.24]) than in treatment-responsive patients (Mean[SD] = 1.38 [0.23]), (T[35] = 2.34, P = .025, 2-tailed), with a large effect size of d = 0.76. A model assuming 2 populations showed a 25% improvement in the fit of the Akaike weights (0.55) over a model assuming 1 population (0.44), producing group values almost identical to actual group means. Increased anterior cingulate glutamate level is associated with treatment-resistant schizophrenia. This appears to be a stable neurobiological trait of treatment-resistant patients. We discuss possible explanations for glutamatergic dysfunction playing a significant role in resistance to conventional antipsychotic treatments, which are all dopamine-2 receptor blockers. Our findings suggest that glutamatergic treatments may be particularly effective in resistant patients and that 1H-MRS glutamate indices can potentially have clinical use. © The Author 2015. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email

  11. Predicting and Monitoring Cancer Treatment Response with DW-MRI

    PubMed Central

    Thoeny, Harriet C.; Ross, Brian D.

    2010-01-01

    An imaging biomarker that would provide for an early quantitative metric of clinical treatment response in cancer patients would provide for a paradigm shift in cancer care. Currently, non-image based clinical outcome metrics include morphology, clinical and laboratory parameters however, these are obtained relatively late following treatment. Diffusion-weighted MRI (DW-MRI) holds promise for use as a cancer treatment response biomarker as it is sensitive to macromolecular and microstructural changes which can occur at the cellular level earlier than anatomical changes during therapy. Studies have shown that successful treatment of a many tumor types can be detected using DW-MRI as an early increase in the apparent diffusion coefficient (ADC) values. Additionally, low pre-treatment ADC values of various tumors are often predictive of better outcome. These capabilities, once validated, could provide for an important opportunity to individualize therapy thereby minimizing unnecessary systemic toxicity associated with ineffective therapies with the additional advantage of improving overall patient health care and associated costs. In this report, we provide a brief technical overview of DW-MRI acquisition protocols, quantitative image analysis approaches and review studies which have implemented DW-MRI for the purpose of early prediction of cancer treatment response. PMID:20575076

  12. Predictors of treatment response to brief behavioral treatment of insomnia (BBTI) in older adults.

    PubMed

    Troxel, Wendy M; Conrad, Tyler S; Germain, Anne; Buysse, Daniel J

    2013-12-15

    The extant literature on predictors of treatment response to behavioral treatments for insomnia is equivocal and limited in scope. The current study examined demographic, clinical, and sleep characteristics as predictors of clinically significant treatment response to brief behavioral treatment of insomnia (BBTI) in older adults with insomnia. Thirty-nine older adults with insomnia (67% females, mean age: 72.54 years) were randomized to BBTI treatment. Treatment outcomes were defined according to 2 criteria: (1) "response," defined as change in Pittsburgh Sleep Quality Index (PSQI) score ≥ 3 points or increase in sleep diary sleep efficiency ≥ 10%); or (2) remission, defined as absence of a clinical diagnosis of insomnia according to standard diagnostic criteria. Logistic regression examined whether baseline demographic, clinical, or sleep characteristics predicted treatment outcomes at 1 month follow-up. Demographic variables did not predict treatment outcomes for either criterion. Higher anxiety, depression, poorer sleep quality, and longer polysomnography (PSG)-assessed sleep latency predicted greater likelihood of response at follow-up (p < 0.05). Longer sleep duration at baseline (measured by sleep diary and PSG) predicted greater likelihood of the remission at follow-up (p < 0.05). Patients with insomnia who have greater distress at baseline or prolonged sleep latency are more likely to show positive response to BBTI. In contrast, short sleepers at baseline are less likely to have resolution of insomnia diagnosis following BBTI, perhaps due to the sleep restriction component of the treatment. Identifying the characteristics that predict positive BBTI treatment outcomes can facilitate personalized behavioral treatments to improve outcomes.

  13. Peer-nominated deviant talk within residential treatment: individual and group influences on treatment response.

    PubMed

    Zakriski, Audrey L; Wright, Jack C; Cardoos, Stephanie L

    2011-10-01

    This research examined deviant talk during summer residential treatment using peer nominations and extensive field observations. Participants were 239 youth (M (age) = 12.62, SD = 2.60; 67% male), nested in 26 treatment groups. Deviant talk was present in this setting, showed individual differences, and increased over time, especially for younger boys. As expected, its relationship to treatment response was moderated by peer behavior. Initial levels of individual deviant talk were related to clinical improvement, but primarily when peer deviant talk was low. Initial levels of peer deviant talk were related to higher than expected end of treatment aggression, especially for youth who were high in deviant talk. Deviant talk effects were observed for staff impressions of change and observations of aggression and adjustment. Initial antisocial behavior affected whether individual or peer levels of deviant talk more heavily influenced treatment response. Implications for clinical assessment and treatment monitoring are discussed.

  14. The Antidepressant Treatment Response Index as a Predictor of Reboxetine Treatment Outcome in Major Depressive Disorder.

    PubMed

    Caudill, Marissa M; Hunter, Aimee M; Cook, Ian A; Leuchter, Andrew F

    2015-10-01

    Biomarkers to predict clinical outcomes early during the treatment of major depressive disorder (MDD) could reduce suffering and improve outcomes. A quantitative electroencephalogram (qEEG) biomarker, the Antidepressant Treatment Response (ATR) index, has been associated with outcomes of treatment with selective serotonin reuptake inhibitor antidepressants in patients with MDD. Here, we report the results of a post hoc analysis initiated to evaluate whether the ATR index may also be associated with reboxetine treatment outcome, given that its putative mechanism of action is via norepinephrine reuptake inhibition (NRI). Twenty-five adults with MDD underwent qEEG studies during open-label treatment with reboxetine at doses of 8 to 10 mg daily for 8 weeks. The ATR index calculated after 1 week of reboxetine treatment was significantly associated with overall Hamilton Depression Rating Scale (HAM-D) improvement at week 8 (r=0.605, P=.001), even after controlling for baseline depression severity (P=.002). The ATR index predicted response (≥50% reduction in HAM-D) with 70.6% sensitivity and 87.5% specificity, and remission (final HAM-D≤7) with 87.5% sensitivity and 64.7% specificity. These results suggest that the ATR index may be a useful biomarker of clinical response during NRI treatment of adults with MDD. Future studies are warranted to investigate further the potential utility of the ATR index as a predictor of noradrenergic antidepressant treatment response.

  15. Does Temperament Moderate Treatment Response in Adolescent Substance Use Disorders?

    ERIC Educational Resources Information Center

    Burleson, Joseph A.; Kaminer, Yifrah

    2008-01-01

    To assess whether temperament moderates response to treatment for substance use disorders (SUD), n = 88 consecutively referred adolescents with SUD were randomized to cognitive-behavioral (CBT) or psychoeducational (PET) therapies. Principal components analyses reduced the 10-attribute Dimensions of Temperament Revised (DOTS-R) to three factors…

  16. Rethinking responsibility in offenders with acquired paedophilia: punishment or treatment?

    PubMed

    Gilbert, Frédéric; Focquaert, Farah

    2015-01-01

    This article reviews the current neurobiological literature on the aetiology of developmental and acquired paedophilia and examines what the consequences could be in terms of responsibility and treatment for the latter. Addressing the question of responsibility and punishment of offenders with acquired paedophilia from a neurobiological perspective is controversial. Consequently it is essential to avoid hasty conclusions based strictly on neurobiological abnormality justifications. This study establishes a distinction between developmental and acquired paedophilia. The article investigates whether offenders who fulfil the diagnosis of acquired paedophilia should be held fully responsible, particularly in cases where the offender's conduct appears to result from volitionally controlled behaviour that is seemingly incompatible with a neurological cause. Moreover, the article explores how responsibility can be compromised when offenders with acquired paedophilia have (partially) preserved moral knowledge despite their sexual disorder. The article then examines the option of offering mandatory treatment as an alternative to imprisonment for offenders with acquired paedophilia. Furthermore, the article addresses the ethical issues related to offering any form of quasi-coercive treatment as a condition of release. This study concludes that decisions to fully or partially excuse an individual who fulfil the diagnosis of acquired paedophilia should take all relevant information into account, both neurobiological and other environmental evidence, and should proceed on a careful case by case analysis before sentencing or offering treatment. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Poroelastic response of geothermal reservoirs during hydraulic stimulation treatment

    NASA Astrophysics Data System (ADS)

    Jacquey, Antoine; Urpi, Luca; Cacace, Mauro; Blöcher, Guido; Zimmermann, Günter; Scheck-Wenderoth, Magdalena

    2017-04-01

    Enhanced geothermal systems (EGS) are engineered reservoirs developed to extract heat from low permeability and low porosity geological formations. Cyclic hydraulic stimulation treatments are used in such a context to create hydraulic fractures, minimizing the fluid injected volume (recently proposed as a mitigation strategy for induced seismicity) to gain access to the target formation fluids, drain the geothermal fluid and therefore increase the overall productivity of the geothermal reservoir. During these operations, successive cycles of injection of high flow rates are conducted to decrease the effective minimum principal stress, and therefore the tensile strength of the material, developing a hydraulic fracture. Opening of these newly developed fractures induces an additional deformation of the reservoir rocks. In this study, the poroelastic response resulting from induced deformation during cyclic hydraulic stimulation treatment of a well is investigated using hydromechanical coupling between pore pressure variations and solid rock deformation. The effects of this poroelastic response on the hydromechanical state of a reservoir is illustrated by means of field measurements of a cyclic hydraulic stimulation treatment conducted at the Groß Schönebeck geothermal research site in August 2007. This study points out that a nonlinear pore pressure response arises within the reservoir rocks due to the deformation generated by the stimulation treatment. It is shown here that the 3D poroelastic response of the reservoir leads to an unexpected quasi-instantaneous pore pressure increase in a neighbor monitoring well located approximatively 475 m away from the stimulated well at reservoir depth.

  18. Does Temperament Moderate Treatment Response in Adolescent Substance Use Disorders?

    ERIC Educational Resources Information Center

    Burleson, Joseph A.; Kaminer, Yifrah

    2008-01-01

    To assess whether temperament moderates response to treatment for substance use disorders (SUD), n = 88 consecutively referred adolescents with SUD were randomized to cognitive-behavioral (CBT) or psychoeducational (PET) therapies. Principal components analyses reduced the 10-attribute Dimensions of Temperament Revised (DOTS-R) to three factors…

  19. Parental Marital Discord and Treatment Response in Depressed Adolescents

    ERIC Educational Resources Information Center

    Amaya, Meredith M.; Reinecke, Mark A.; Silva, Susan G.; March, John S.

    2011-01-01

    Evidence suggests that parental marital discord contributes to the development of internalizing and externalizing symptoms in children and adolescents. Few studies, however, have examined the association between parental marital discord and youth's response to treatment. The present study examined the impact of interparental discord on treatment…

  20. Parental Marital Discord and Treatment Response in Depressed Adolescents

    ERIC Educational Resources Information Center

    Amaya, Meredith M.; Reinecke, Mark A.; Silva, Susan G.; March, John S.

    2011-01-01

    Evidence suggests that parental marital discord contributes to the development of internalizing and externalizing symptoms in children and adolescents. Few studies, however, have examined the association between parental marital discord and youth's response to treatment. The present study examined the impact of interparental discord on treatment…

  1. Personality, Stressful Life Events, and Treatment Response in Major Depression

    ERIC Educational Resources Information Center

    Bulmash, Eric; Harkness, Kate L.; Stewart, Jeremy G.; Bagby, R. Michael

    2009-01-01

    The current study examined whether the personality traits of self-criticism or dependency moderated the effect of stressful life events on treatment response. Depressed outpatients (N = 113) were randomized to 16 weeks of cognitive-behavioral therapy, interpersonal psychotherapy, or antidepressant medication (ADM). Stressful life events were…

  2. Personality, Stressful Life Events, and Treatment Response in Major Depression

    ERIC Educational Resources Information Center

    Bulmash, Eric; Harkness, Kate L.; Stewart, Jeremy G.; Bagby, R. Michael

    2009-01-01

    The current study examined whether the personality traits of self-criticism or dependency moderated the effect of stressful life events on treatment response. Depressed outpatients (N = 113) were randomized to 16 weeks of cognitive-behavioral therapy, interpersonal psychotherapy, or antidepressant medication (ADM). Stressful life events were…

  3. Neoadjuvant treatment for advanced esophageal cancer: response assessment before surgery and how to predict response to chemoradiation before starting treatment

    PubMed Central

    Hölscher, Arnulf H.; Schmidt, Matthias; Warnecke-Eberz, Ute

    2015-01-01

    Patients with advanced esophageal cancer (T3-4, N) have a poor prognosis. Chemoradiation or chemotherapy before esophagectomy with adequate lymphadenectomy is the standard treatment for patients with resectable advanced esophageal carcinoma. However, only patients with major histopathologic response (regression to less than 10% of the primary tumor) after preoperative treatment will have a prognostic benefit of preoperative chemoradiation. Using current therapy regimens about 40% to 50% of the patients show major histopathological response. The remaining cohort does not benefit from this neoadjuvant approach but might benefit from earlier surgical resection. Therefore, it is an aim to develop tools for response prediction before starting the treatment and for early response assessment identifying responders. The current review discusses the different imaging techniques and the most recent studies about molecular markers for early response prediction. The results show that [18F]-fluorodeoxyglucose-positron emission tomography (FDG-PET) has a good sensitivity but the specificity is not robust enough for routine clinical use. Newer positron emission tomography detector technology, the combination of FDG-PET with computed tomography, additional evaluation criteria and standardization of evaluation may improve the predictive value. There exist a great number of retrospective studies using molecular markers for prediction of response. Until now the clinical use is missing. But the results of first prospective studies are promising. A future perspective may be the combination of imaging technics and special molecular markers for individualized therapy. Another aspect is the response assessment after finishing neoadjuvant treatment protocol. The different clinical methods are discussed. The results show that until now no non-invasive method is valid enough to assess complete histopathological response. PMID:26157318

  4. The evolution of the female sexual response concept: treatment implications.

    PubMed

    Damjanović, Aleksandar; Duisin, Dragana; Barisić, Jasmina

    2013-01-01

    Sexual dysfunctions have been the most prevalent group of sexual disorders and include a large number of populations of both sexes.The research of sexual behavior and treatment of women with sexual distress arises many questions related to differences in sexual response of men and women. The conceptualization of this response in modern sexology has changed over time.The objective of our paper was to present the changes and evolution of the female's sexual response concept in a summarized and integrated way, to analyze the expanded and revised definitions of the female sexual response as well as implications and recommendations of new approaches to diagnostics and treatment according to the established changes.The lack of adequate empirical basis of the female sexual response model is a critical question in the literature dealing with this issue. Some articles report that linear models demonstrate more correctly and precisely the sexual response of women with normal sexual functions in relation to women with sexual dysfunction. Modification of this model later resulted in a circular model which more adequately presented the sexual response of women with sexual function disorder than of women with normal sexual function.The nonlinear model of female sexual response constructed by Basson incorporates the value of emotional intimacy, sexual stimulus and satisfaction with the relationship. Female functioning is significantly affected by multiple psychosocial factors such as satisfaction with the relationship, self-image, earlier negative sexual experience, etc. Newly revised, expanded definitions of female sexual dysfunction try to contribute to new knowledge about a highly contextual nature of woman's sexuality so as to enhance clinical treatment of dysfunctions.The definitions emphasize the evaluation of the context of women's problematic sexual experiences.

  5. Rapid response in psychological treatments for binge eating disorder.

    PubMed

    Hilbert, Anja; Hildebrandt, Thomas; Agras, W Stewart; Wilfley, Denise E; Wilson, G Terence

    2015-06-01

    Analysis of short- and long-term effects of rapid response across 3 different treatments for binge eating disorder (BED). In a randomized clinical study comparing interpersonal psychotherapy (IPT), cognitive-behavioral therapy guided self-help (CBTgsh), and behavioral weight loss (BWL) treatment in 205 adults meeting Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV; APA, 1994) criteria for BED, the predictive value of rapid response, defined as ≥70% reduction in binge eating by Week 4, was determined for remission from binge eating and global eating disorder psychopathology at posttreatment, 6-, 12-, 18-, and 24-month follow-ups. Rapid responders in CBTgsh, but not in IPT or BWL, showed significantly greater rates of remission from binge eating than nonrapid responders, which was sustained over the long term. Rapid and nonrapid responders in IPT and rapid responders in CBTgsh showed a greater remission from binge eating than nonrapid responders in CBTgsh and BWL. Rapid responders in CBTgsh showed greater remission from binge eating than rapid responders in BWL. Although rapid responders in all treatments had lower global eating disorder psychopathology than nonrapid responders in the short term, rapid responders in CBTgsh and IPT were more improved than those in BWL and nonrapid responders in each treatment. Rapid responders in BWL did not differ from nonrapid responders in CBTgsh and IPT. Rapid response is a treatment-specific positive prognostic indicator of sustained remission from binge eating in CBTgsh. Regarding an evidence-based, stepped-care model, IPT, equally efficacious for rapid and nonrapid responders, could be investigated as a second-line treatment in case of nonrapid response to first-line CBTgsh. (c) 2015 APA, all rights reserved).

  6. Rapid Response in Psychological Treatments for Binge-Eating Disorder

    PubMed Central

    Hilbert, Anja; Hildebrandt, Thomas; Agras, W. Stewart; Wilfley, Denise E.; Wilson, G. Terence

    2015-01-01

    Objective Analysis of short- and long-term effects of rapid response across three different treatments for binge-eating disorder (BED). Method In a randomized clinical study comparing interpersonal psychotherapy (IPT), cognitive-behavioral guided self-help (CBTgsh), and behavioral weight loss (BWL) treatment in 205 adults meeting DSM-IV criteria for BED, the predictive value of rapid response, defined as ≥ 70% reduction in binge-eating by week four, was determined for remission from binge-eating and global eating disorder psychopathology at posttreatment, 6-, 12-, 18-, and 24-month follow-up. Results Rapid responders in CBTgsh, but not in IPT or BWL, showed significantly greater rates of remission from binge-eating than non-rapid responders, which was sustained over the long term. Rapid and non-rapid responders in IPT and rapid responders in CBTgsh showed a greater remission from binge-eating than non-rapid responders in CBTgsh and BWL. Rapid responders in CBTgsh showed greater remission from binge-eating than rapid responders in BWL. Although rapid responders in all treatments had lower global eating disorder psychopathology than non-rapid responders in the short term, rapid responders in CBTgsh and IPT were more improved than those in BWL and non-rapid responders in each treatment. Rapid responders in BWL did not differ from non-rapid responders in CBTgsh and IPT. Conclusions Rapid response is a treatment-specific positive prognostic indicator of sustained remission from binge-eating in CBTgsh. Regarding an evidence-based stepped care model, IPT, equally efficacious for rapid and non-rapid responders, could be investigated as a second-line treatment in case of non-rapid response to first-line CBTgsh. PMID:25867446

  7. Trajectories of Response to Treatment for Posttraumatic Stress Disorder

    PubMed Central

    Stein, Nathan R.; Dickstein, Benjamin D.; Schuster, Jennifer; Litz, Brett T.; Resick, Patricia A.

    2012-01-01

    Research on the predictors of response to cognitive-behavioral treatments for PTSD has often produced inconsistent or ambiguous results. We argue this is in part due to the use of statistical techniques that explore relationships among the entire sample of participants rather than homogeneous subgroups. Using two large randomized controlled trials of Cognitive Processing Therapy (CPT), CPT components, and Prolonged Exposure, we employed growth mixture modeling to identify distinct trajectories of treatment response and to determine the predictors of those trajectories. We determined that the participants' trajectories could be best represented by two latent classes, which we subsequently labeled responders (87% of the sample) and non-responders (13% of the sample). Notably, there was not a separate class for partial responders. Assignment to the non-responder class was associated with receiving the written accounts (WA) component of CPT, a pre-treatment diagnosis of major depression (MDD), and more pre-treatment hyperarousal symptoms. Thus, it appears that some individuals do not benefit from merely writing about their trauma and processing it with the therapist; they may also need to engage in cognitive restructuring to successfully ameliorate their symptoms. Additionally, those who meet criteria for MDD or have high levels of hyperarousal at the onset of treatment might require additional treatment or support. PMID:23046781

  8. Dynamic Rendering of the Heterogeneous Cell Response to Anticancer Treatments

    PubMed Central

    Falcetta, Francesca; Lupi, Monica; Colombo, Valentina; Ubezio, Paolo

    2013-01-01

    The antiproliferative response to anticancer treatment is the result of concurrent responses in all cell cycle phases, extending over several cell generations, whose complexity is not captured by current methods. In the proposed experimental/computational approach, the contemporary use of time-lapse live cell microscopy and flow cytometric data supported the computer rendering of the proliferative process through the cell cycle and subsequent generations during/after treatment. The effects of treatments were modelled with modules describing the functional activity of the main pathways causing arrest, repair and cell death in each phase. A framework modelling environment was created, enabling us to apply different types of modules in each phase and test models at the complexity level justified by the available data. We challenged the method with time-course measures taken in parallel with flow cytometry and time-lapse live cell microscopy in X-ray-treated human ovarian cancer cells, spanning a wide range of doses. The most suitable model of the treatment, including the dose-response of each effect, was progressively built, combining modules with a rational strategy and fitting simultaneously all data of different doses and platforms. The final model gave for the first time the complete rendering in silico of the cycling process following X-ray exposure, providing separate and quantitative measures of the dose-dependence of G1, S and G2M checkpoint activities in subsequent generations, reconciling known effects of ionizing radiations and new insights in a unique scenario. PMID:24146610

  9. Covariate-adjusted response-adaptive designs for longitudinal treatment responses: PEMF trial revisited.

    PubMed

    Biswas, Atanu; Park, Eunsik; Bhattacharya, Rahul

    2012-08-01

    Response-adaptive designs have become popular for allocation of the entering patients among two or more competing treatments in a phase III clinical trial. Although there are a lot of designs for binary treatment responses, the number of designs involving covariates is very small. Sometimes the patients give repeated responses. The only available response-adaptive allocation design for repeated binary responses is the urn design by Biswas and Dewanji [Biswas A and Dewanji AA. Randomized longitudinal play-the-winner design for repeated binary data. ANZJS 2004; 46: 675-684; Biswas A and Dewanji A. Inference for a RPW-type clinical trial with repeated monitoring for the treatment of rheumatoid arthritis. Biometr J 2004; 46: 769-779.], although it does not take care of the covariates of the patients in the allocation design. In this article, a covariate-adjusted response-adaptive randomisation procedure is developed using the log-odds ratio within the Bayesian framework for longitudinal binary responses. The small sample performance of the proposed allocation procedure is assessed through a simulation study. The proposed procedure is illustrated using some real data set.

  10. Does temperament moderate treatment response in adolescent substance use disorders?

    PubMed

    Kaminer, Yifrah; Burleson, Joseph A

    2008-01-01

    To assess whether temperament moderates response to treatment for substance use disorders (SUD), n = 88 consecutively referred adolescents with SUD were randomized to cognitive- behavioral (CBT) or psychoeducational (PET) therapies. Principal components analyses reduced the 10-attribute Dimensions of Temperament Revised (DOTS-R) to three factors (Rhythmicity, Activity/Flexibility, and Mood/Sociability). Three response domains (Alcohol Use, Other Substance Use, and Psychological Function) from the Teen Addiction Severity Index (T-ASI) were assessed at baseline and at 3-month post-treatment completion. There was a significant moderator effect on Treatment only for Rhythmicity on T-ASI Alcohol and Psychological domains. For Alcohol use, for youth with poor levels of Rhythmicity, only PET effected significant improvement, whereas for youth with good levels of Rhythmicity, no treatment differences emerged. For Psychological function, for youth with good levels of Rhythmicity, only CBT effected significant improvement, whereas for youth with poor levels of Rhythmicity, no treatment differences emerged. Implications of these findings are discussed.

  11. Poor Response to Periodontal Treatment May Predict Future Cardiovascular Disease.

    PubMed

    Holmlund, A; Lampa, E; Lind, L

    2017-07-01

    Periodontal disease has been associated with cardiovascular disease (CVD), but whether the response to the treatment of periodontal disease affects this association has not been investigated in any large prospective study. Periodontal data obtained at baseline and 1 y after treatment were available in 5,297 individuals with remaining teeth who were treated at a specialized clinic for periodontal disease. Poor response to treatment was defined as having >10% sites with probing pocket depth >4 mm deep and bleeding on probing at ≥20% of the sites 1 y after active treatment. Fatal/nonfatal incidence rate of CVD (composite end point of myocardial infarction, stroke, and heart failure) was obtained from the Swedish cause-of-death and hospital discharge registers. Poisson regression analysis was performed to analyze future risk of CVD. During a median follow-up of 16.8 y (89,719 person-years at risk), those individuals who did not respond well to treatment (13.8% of the sample) had an increased incidence of CVD ( n = 870) when compared with responders (23.6 vs. 15.3%, P < 0.001). When adjusting for calendar time, age, sex, educational level, smoking, and baseline values for bleeding on probing, probing pocket depth >4 mm, and number of teeth, the incidence rate ratio for CVD among poor responders was 1.28 (95% CI, 1.07 to 1.53; P = 0.007) as opposed to good responders. The incidence rate ratio among poor responders increased to 1.39 (95% CI, 1.13 to 1.73; P = 0.002) for those with the most remaining teeth. Individuals who did not respond well to periodontal treatment had an increased risk for future CVD, indicating that successful periodontal treatment might influence progression of subclinical CVD.

  12. Measurements of treatment response in childhood acute leukemia

    PubMed Central

    Coustan-Smith, Elaine

    2012-01-01

    Measuring response to chemotherapy is a backbone of the clinical management of patients with acute leukemia. This task has historically relied on the ability to identify leukemic cells among normal bone marrow cells by their morphology. However, more accurate ways to identify leukemic cells have been developed, which allow their detection even when they are present in small numbers that would be impossible to be recognized by microscopic inspection. The levels of such minimal residual disease (MRD) are now widely used as parameters for risk assignment in acute lymphoblastic leukemia (ALL) and increasingly so in acute myeloid leukemia (AML). However, different MRD monitoring methods may produce discrepant results. Moreover, results of morphologic examination may be in stark contradiction to MRD measurements, thus creating confusion and complicating treatment decisions. This review focusses on the relation between results of different approaches to measure response to treatment and define relapse in childhood acute leukemia. PMID:23320002

  13. Idiopathic Hypersomnia: Clinical Features and Response to Treatment

    PubMed Central

    Ali, Mohsin; Auger, R. Robert; Slocumb, Nancy L.; Morgenthaler, Timothy I.

    2009-01-01

    Objective: A recent American Academy of Sleep Medicine publication identified a need for research regarding idiopathic hypersomnia. We describe various clinical and polysomnographic features of patients with idiopathic hypersomnia, with an emphasis on response to pharmacotherapy. Methods: A retrospective review of our database initially identified 997 patients, utilizing “idiopathic hypersomnia,” “hypersomnia NOS,” and “primary hypersomnia” as keywords. The charts of eligible patients were examined in detail, and data were abstracted and analyzed. Response to treatment was graded utilizing an internally developed scale. Results: Eighty-five patients were ultimately identified (65% female). Median (interquartile range) ages of onset and diagnosis were 19.6 (15.5) and 33.7 (15.5), respectively. During a median follow-up duration of 2.4 (4.7) years, 65% of patients demonstrated a “complete response” to pharmacotherapy as assessed by the authors' grading schema. Methylphenidate was most commonly used as a first-line agent prior to December 1998, but subsequently, modafinil became the most common first drug. At the last recorded follow-up visit, 92% of patients were on monotherapy, with greater representation of methylphenidate versus modafinil (51% vs. 32%). Among these patients, methylphenidate produced a higher percentage of “complete” or “partial” responses than modafinil, although statistical significance was not reached (38/40 [ 95%] vs 22/25 [88%], respectively, p = 0.291). Conclusions: The majority of patients with idiopathic hypersomnia respond well to treatment. Methylphenidate is chosen more often than modafinil as final monotherapy in the treatment of idiopathic hypersomnia, despite the fact that it is less commonly used initially. Further prospective comparisons of medications should be explored. Citation: Ali M; Auger RR; Slocumb NL; Morgenthaler TI. Idiopathic hypersomnia: clinical features and response to treatment. J Clin Sleep

  14. Measurement of response to treatment in colorectal liver metastases.

    PubMed Central

    Dworkin, M. J.; Burke, D.; Earlam, S.; Fordy, C.; Allen-Mersh, T. G.

    1995-01-01

    Assessment of tumour response to chemotherapy is important when assessing efficacy of treatment and comparing differing therapeutic regimens. Percentage hepatic replacement (PHR) is commonly used to assess response to treatment of colorectal hepatic metastases. PHR is dependent not only on tumour volume, but also on hepatic parenchymal volume. The effect of tumour growth on hepatic parenchymal volume is unclear but is of importance owing to its effect on PHR. We assessed tumour and hepatic parenchymal weights in an animal tumour model using dissection, and tumour and hepatic parenchymal volumes in patients with colorectal hepatic metastases using CT scanning, in order to establish how hepatic parenchyma varied with change in metastasis size. There was no significant correlation between tumour and liver parenchyma in either the animal model (r = -0.03, P > 0.05) or the patient study (r = 0.3, P < 0.05). This suggests that hepatic parenchymal volume was preserved in the presence of increasing tumour volume. In a further study of computerised tomographic (CT) scans before and after treatment in patients whose tumours either responded to chemotherapy or continued to grow, change in PHR (median proportion of PHR change = 0.40) significantly (P = 0.04) underestimated the change in tumour volume (median proportion of tumour volume change = 0.56), particularly at higher (> 400 ml) volumes. There was good correlation between change in tumour volume and WHO criteria in assigning patients to tumour growth, stable disease or tumour response categories. This study suggests that, in clinical trials comparing colorectal liver metastasis treatments, metastasis volume and not PHR should be used to assess extent of disease and the effect of treatment. PMID:7710957

  15. Image Registration for Quantitative Parametric Response Mapping of Cancer Treatment Response1

    PubMed Central

    Boes, Jennifer L; Hoff, Benjamin A; Hylton, Nola; Pickles, Martin D; Turnbull, Lindsay W; Schott, Anne F; Rehemtulla, Alnawaz; Chamberlain, Ryan; Lemasson, Benjamin; Chenevert, Thomas L; Galbán, Craig J; Meyer, Charles R; Ross, Brian D

    2014-01-01

    Imaging biomarkers capable of early quantification of tumor response to therapy would provide an opportunity to individualize patient care. Image registration of longitudinal scans provides a method of detecting treatment associated changes within heterogeneous tumors by monitoring alterations in the quantitative value of individual voxels over time, which is unattainable by traditional volumetric-based histogram methods. The concepts involved in the use of image registration for tracking and quantifying breast cancer treatment response using parametric response mapping (PRM), a voxel-based analysis of diffusion-weighted magnetic resonance imaging (DW-MRI) scans, are presented. Application of PRM to breast tumor response detection is described, wherein robust registration solutions for tracking small changes in water diffusivity in breast tumors during therapy are required. Methodologies that employ simulations are presented for measuring expected statistical accuracy of PRM for response assessment. Test-retest clinical scans are used to yield estimates of system noise to indicate significant changes in voxel-based changes in water diffusivity. Overall, registration-based PRM image analysis provides significant opportunities for voxel-based image analysis to provide the required accuracy for early assessment of response to treatment in breast cancer patients receiving neoadjuvant chemotherapy. PMID:24772213

  16. Predicting response to treatment in chronic inflammatory demyelinating polyradiculoneuropathy.

    PubMed

    Chan, Y-C; Allen, D C; Fialho, D; Mills, K R; Hughes, R A C

    2006-01-01

    To discover whether Inflammatory Neuropathy Cause and Treatment Group (INCAT) electrophysiological criteria for demyelinating neuropathy predict response to immunotherapy in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). This was a retrospective case note study of patients who had attended Guy's Hospital Peripheral Nerve Clinic between January 2001 and March 2004, been diagnosed as having CIDP, and given treatment with corticosteroids, intravenous immunoglobulin (IVIg), or plasma exchange (PE). Patients' nerve conduction studies (NCS) were reviewed for evidence of demyelination and whether the abnormalities fulfilled modified INCAT electrophysiological criteria. Patients whose NCS fulfilled the criteria were assigned to the neurophysiologically definite CIDP group, while those that did not were labelled as neurophysiologically probable CIDP. Responses to any of the three immunotherapy agents were compared between the two groups. Out of 50 patients, 27 (54%) were classified as neurophysiologically definite and 23 (46%) as neurophysiologically probable CIDP patients. Twenty (74%) neurophysiologically definite and 17 (73.9%) neurophysiologically probable CIDP patients responded to treatment. INCAT electrophysiological criteria did not predict a higher rate of response to immunotherapy. Neurophysiologically probable CIDP patients should be given a trial of immunotherapy.

  17. Predicting response to treatment in chronic inflammatory demyelinating polyradiculoneuropathy

    PubMed Central

    Chan, Y‐C; Allen, D C; Fialho, D; Mills, K R; Hughes, R A C

    2006-01-01

    Objective To discover whether Inflammatory Neuropathy Cause and Treatment Group (INCAT) electrophysiological criteria for demyelinating neuropathy predict response to immunotherapy in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Methods This was a retrospective case note study of patients who had attended Guy's Hospital Peripheral Nerve Clinic between January 2001 and March 2004, been diagnosed as having CIDP, and given treatment with corticosteroids, intravenous immunoglobulin (IVIg), or plasma exchange (PE). Patients' nerve conduction studies (NCS) were reviewed for evidence of demyelination and whether the abnormalities fulfilled modified INCAT electrophysiological criteria. Patients whose NCS fulfilled the criteria were assigned to the neurophysiologically definite CIDP group, while those that did not were labelled as neurophysiologically probable CIDP. Responses to any of the three immunotherapy agents were compared between the two groups. Results Out of 50 patients, 27 (54%) were classified as neurophysiologically definite and 23 (46%) as neurophysiologically probable CIDP patients. Twenty (74%) neurophysiologically definite and 17 (73.9%) neurophysiologically probable CIDP patients responded to treatment. Conclusions INCAT electrophysiological criteria did not predict a higher rate of response to immunotherapy. Neurophysiologically probable CIDP patients should be given a trial of immunotherapy. PMID:16361609

  18. Frontocingulate Dysfunction in Depression: Toward Biomarkers of Treatment Response

    PubMed Central

    Pizzagalli, Diego A

    2011-01-01

    Increased rostral anterior cingulate cortex (rACC) activity has emerged as a promising predictor of treatment response in depression, but neither the reliability of this relationship nor the mechanisms supporting it have been thoroughly investigated. This review takes a three-pronged approach to these issues. First, I present a meta-analysis demonstrating that the relationship between resting rACC activity and treatment response is robust. Second, I propose that the rACC plays a key role in treatment outcome because of its ‘hub' position in the default network. Specifically, I hypothesize that elevated resting rACC activity confers better treatment outcomes by fostering adaptive self-referential processing and by helping to recalibrate relationships between the default network and a ‘task-positive network' that comprises dorsolateral prefrontal and dorsal cingulate regions implicated in cognitive control. Third, I support this hypothesis by reviewing neuropsychological, electrophysiological, and neuroimaging data on frontocingulate dysfunction in depression. The review ends with a discussion of the limitations of current work and future directions. PMID:20861828

  19. Adolescents with Internet Gaming Disorder (IGD): profiles and treatment response.

    PubMed

    Martín-Fernández, María; Matalí, Josep Lluís; García-Sánchez, Sara; Pardo, Marta; Lleras, María; Castellano-Tejedor, Carmina

    2016-10-07

    Demand for treatment for problems related to the use of video games have increased significantly in adolescents. Most cases have a comorbid mental disorder that jeopardises both pathologies. The aim of this study is to describe profiles of adolescents with Internet Gaming Disorder (IGD) according to comorbidity and analyze treatment response at 3 and 6 months. A sample of 86 patients which consulted in the Addictive Behavior Unit of a hospital was assessed with diagnostic criteria for IGD, the interview K-SADS-PL for mental disorders and the Clinical Global Impression (CGI) to treatment progress. Of the initial sample, 68,6% (n = 59) met diagnostic criteria for IGD. Of these, the 45,76% matched an internalizing profile, presenting comorbidity with Mood Disorders (44,4%), Anxiety Disorders (44,4%) and Personality Disorders (11,1%). The externalizing profile would comprise 52,54% of the sample presenting Disruptive Behavior Disorder (48,4%=, ADHD (29%) and Disruptive Behavior Disorders not otherwise specified (22,6%). Unlike externalizing, the internalizing patients had a family history of psychiatric problems (63%), difficulties in social relationships (77,8%) and seemed to use video games preferably to escape discomfort (66,7%). After 3 months the externalizing profile showed improvements. Comorbid disorders allow the discrimination of two IGD profiles in adolescents and these could influence treatment response. Therefore, it is important to assess comorbidities to design a more accurate intervention focused on the specificities of each profile.

  20. Predictive response biomarkers in rectal cancer neoadjuvant treatment.

    PubMed

    Agostini, Marco; Crotti, Sara; Bedin, Chiara; Cecchin, Erika; Maretto, Isacco; D'Angelo, Edoardo; Pucciarelli, Salvatore; Nitti, Donato

    2014-01-01

    Locally advanced rectal cancer (RC) treatment is a challenge, because RC has a high rate of local recurrence. To date preoperative chemoradiotherapy (pCRT) is widely accepted as standard protocol of care for middle-low RC, but complete tumour response rate ranges from 4 to 44% and 5-year local recurrence rate is 6%. Better understanding of molecular biology and carcinogenesis pathways could be used both for pre-neoplastic lesions and locally recurrence diagnosis, and for tumour response prediction to therapy. Circulating molecules, gene expression and protein signature are promising sources to biomarker discovery. Several studies have evaluated potential predictors of response and recently, cell-free Nucleic Acid levels have been associated to tumour response to neoadjuvant therapies. Alternative method is the serum or plasma proteome and peptidome analysis. It may be ideally suited for its minimal invasiveness and it can be repeated at multiple time points throughout the treatment in contrast to tissue-based methods which still remain the most reliable and specific approach. Many studies have analyzed preoperative rectal tissue prognostic factor, but data are controversial or not confirmed.

  1. Electrochemical treatment of deproteinated whey wastewater and optimization of treatment conditions with response surface methodology.

    PubMed

    Güven, Güray; Perendeci, Altunay; Tanyolaç, Abdurrahman

    2008-08-30

    Electrochemical treatment of deproteinated whey wastewater produced during cheese manufacture was studied as an alternative treatment method for the first time in literature. Through the preliminary batch runs, appropriate electrode material was determined as iron due to high removal efficiency of chemical oxygen demand (COD), and turbidity. The electrochemical treatment conditions were optimized through response surface methodology (RSM), where applied voltage was kept in the range, electrolyte concentration was minimized, waste concentration and COD removal percent were maximized at 25 degrees C. Optimum conditions at 25 degrees C were estimated through RSM as 11.29 V applied voltage, 100% waste concentration (containing 40 g/L lactose) and 19.87 g/L electrolyte concentration to achieve 29.27% COD removal. However, highest COD removal through the set of runs was found as 53.32% within 8h. These results reveal the applicability of electrochemical treatment to the deproteinated whey wastewater as an alternative advanced wastewater treatment method.

  2. Enteric microbiome metabolites correlate with response to simvastatin treatment.

    PubMed

    Kaddurah-Daouk, Rima; Baillie, Rebecca A; Zhu, Hongjie; Zeng, Zhao-Bang; Wiest, Michelle M; Nguyen, Uyen Thao; Wojnoonski, Katie; Watkins, Steven M; Trupp, Miles; Krauss, Ronald M

    2011-01-01

    Although statins are widely prescribed medications, there remains considerable variability in therapeutic response. Genetics can explain only part of this variability. Metabolomics is a global biochemical approach that provides powerful tools for mapping pathways implicated in disease and in response to treatment. Metabolomics captures net interactions between genome, microbiome and the environment. In this study, we used a targeted GC-MS metabolomics platform to measure a panel of metabolites within cholesterol synthesis, dietary sterol absorption, and bile acid formation to determine metabolite signatures that may predict variation in statin LDL-C lowering efficacy. Measurements were performed in two subsets of the total study population in the Cholesterol and Pharmacogenetics (CAP) study: Full Range of Response (FR), and Good and Poor Responders (GPR) were 100 individuals randomly selected from across the entire range of LDL-C responses in CAP. GPR were 48 individuals, 24 each from the top and bottom 10% of the LDL-C response distribution matched for body mass index, race, and gender. We identified three secondary, bacterial-derived bile acids that contribute to predicting the magnitude of statin-induced LDL-C lowering in good responders. Bile acids and statins share transporters in the liver and intestine; we observed that increased plasma concentration of simvastatin positively correlates with higher levels of several secondary bile acids. Genetic analysis of these subjects identified associations between levels of seven bile acids and a single nucleotide polymorphism (SNP), rs4149056, in the gene encoding the organic anion transporter SLCO1B1. These findings, along with recently published results that the gut microbiome plays an important role in cardiovascular disease, indicate that interactions between genome, gut microbiome and environmental influences should be considered in the study and management of cardiovascular disease. Metabolic profiles could

  3. Conventional frequency ultrasonic biomarkers of cancer treatment response in vivo.

    PubMed

    Sadeghi-Naini, Ali; Falou, Omar; Tadayyon, Hadi; Al-Mahrouki, Azza; Tran, William; Papanicolau, Naum; Kolios, Michael C; Czarnota, Gregory J

    2013-06-01

    Conventional frequency quantitative ultrasound in conjunction with textural analysis techniques was investigated to monitor noninvasively the effects of cancer therapies in an in vivo preclinical model. Conventional low-frequency (∼7 MHz) and high-frequency (∼20 MHz) ultrasound was used with spectral analysis, coupled with textural analysis on spectral parametric maps, obtained from xenograft tumor-bearing animals (n = 20) treated with chemotherapy to extract noninvasive biomarkers of treatment response. Results indicated statistically significant differences in quantitative ultrasound-based biomarkers in both low- and high-frequency ranges between untreated and treated tumors 12 to 24 hours after treatment. Results of regression analysis indicated a high level of correlation between quantitative ultrasound-based biomarkers and tumor cell death estimates from histologic analysis. Applying textural characterization to the spectral parametric maps resulted in an even stronger correlation (r (2) = 0.97). The results obtained in this research demonstrate that quantitative ultrasound at a clinically relevant frequency can monitor tissue changes in vivo in response to cancer treatment administration. Using higher order textural information extracted from quantitative ultrasound spectral parametric maps provides more information at a high sensitivity related to tumor cell death.

  4. The myocardial heat shock response following sodium salicylate treatment

    PubMed Central

    Locke, Marius; Atance, Joel

    2000-01-01

    In cultured cells, salicylate has been shown to potentiate the induction of Hsp72 so that a mild heat stress (40°C) in the presence of salicylate induces an Hsp72 response that is similar to a severe heat stress (42°C). To determine whether salicylate can potentiate the myocardial Hsp70 response in vivo and confer protection from an ischemic stress, male Sprague-Dawley rats (250–300 g) were placed into 5 groups: (1) control, (2) salicylate only (400 mg/kg), (3) mild heat stress (40°C for 15 minutes), (4) mild heat stress plus salicylate, and (5) severe heat stress (42°C for 15 minutes). Twenty-four hours following salicylate treatment and/or heat stress, animals were anesthetized, their hearts rapidly isolated, and hemodynamic function evaluated using the Langendorff technique. Hsp72 content was subsequently assessed by Western blotting. Although salicylate in combination with a mild heat stress induced heat shock factor activation, only the hearts from severely heat-stressed animals (42°C) demonstrated a significantly elevated myocardial Hsp72 content and a significantly enhanced postischemic recovery of left ventricular developed pressure and rates of contraction and relaxation. These results support the role for Hsp72 as a protective protein and suggest that neither salicylate treatment alone nor salicylate in combination with a mild heat stress potentiates the myocardial Hsp72 response. PMID:11048658

  5. Changes in Trypanosoma cruzi-specific immune responses following treatment: surrogate markers of treatment efficacy

    PubMed Central

    Laucella, Susana A.; Mazliah, Damián Pérez; Bertocchi, Graciela; Alvarez, María G.; Cooley, Gretchen; Viotti, Rodolfo; Albareda, María C.; Lococo, Bruno; Postan, Miriam; Armenti, Alejandro; Tarleton, Rick L.

    2009-01-01

    Background As many as 20 million people are living with Trypanosoma cruzi infection in Latin American, yet few receive any treatment. The major limitation in developing and evaluating potential new drugs for their efficacy is the lack of reliable tests to assess parasite burden and elimination. Methods Adults volunteers with chronic T. cruzi infection were evaluated clinically and stratified according to the Kuschnir classification. Individuals in group 0 and group 1 clinical status were treated with 5 mg benznidazole/kg/day for 30 days. The changes in T. cruzi-specific T cell and antibody responses, as well as in clinical status, were measured periodically over the 3-5 year follow-up period and compared to pre-treatment conditions and to an untreated control group. Results The frequency of peripheral IFN- g-producing T cells specific for T. cruzi declined as early as 12 months after BZ treatment and subsequently became undetectable in a substantial proportion of treated subjects. Addtionally decreases in antibody responses to a pool of recombinant T. cruzi proteins also declined in many of these same subjects. The shift to negative IFN- g T cell responses was highly associated with an early increase in IFN- g-producing T cells with phenotypic features of effector/effector memory cells in a subset of subjects. Benznidazole treatment also resulted in an increase in naïve and early differentiated memory-like CD8+ T cells in a majority of subjects. Conclusions BZ treatment during chronic Chagas disease has a substantial impact on parasite-specific immune response that is likely to be indicative of treatment efficacy and cure. PMID:19877967

  6. Peripheral biomarkers of cognitive response to dopamine receptor agonist treatment.

    PubMed

    Ersche, Karen D; Roiser, Jonathan P; Lucas, Mark; Domenici, Enrico; Robbins, Trevor W; Bullmore, Edward T

    2011-04-01

    Using biological markers to objectively measure addiction severity or to identify individuals who might benefit most from pro-cognitive treatment could potentially revolutionize neuropsychopharmacology. We investigated the use of dopamine receptor mRNA levels in circulating blood cells as predictors of cognitive response following dopamine agonist treatment, and as biomarkers of the severity of stimulant drug dependence. We employed a double-blind, placebo-controlled cross-over design, administering a single dose of the selective dopamine D(2/3) receptor agonist pramipexole (0.5 mg) to increase dopamine transmission in one session and a placebo treatment in another session in 36 volunteers. Half the volunteers had a formal diagnosis of stimulant dependence, while half had no psychiatric history. Participants performed neurocognitive tests from the CANTAB battery on both occasions, and stimulant-dependent individuals rated drug craving using visual analog scales. Whole-blood mRNA levels were measured for three dopamine-related genes: DRD3 and DRD4 (dopamine receptors), and catechol-O-methyltransferase (COMT; a dopamine catabolic enzyme). Stimulant users performed worse than healthy volunteers on the cognitive tests. The variation in peripheral dopamine D(3) receptor mRNA expression explained over one quarter of the variation in response to pramipexole on the spatial working memory test across all participants. The severity of stimulant dependence was also significantly associated with peripheral COMT mRNA expression in stimulant users. Peripheral expression of dopamine-related genes may be useful as a biomarker of cognitive response to dopamine agonist drugs and of severity of addiction to dopamine-releasing stimulant drugs.

  7. Clinical evaluation of tuberculosis viability microscopy for assessing treatment response.

    PubMed

    Datta, Sumona; Sherman, Jonathan M; Bravard, Marjory A; Valencia, Teresa; Gilman, Robert H; Evans, Carlton A

    2015-04-15

    It is difficult to determine whether early tuberculosis treatment is effective in reducing the infectiousness of patients' sputum, because culture takes weeks and conventional acid-fast sputum microscopy and molecular tests cannot differentiate live from dead tuberculosis. To assess treatment response, sputum samples (n=124) from unselected patients (n=35) with sputum microscopy-positive tuberculosis were tested pretreatment and after 3, 6, and 9 days of empiric first-line therapy. Tuberculosis quantitative viability microscopy with fluorescein diacetate, quantitative culture, and acid-fast auramine microscopy were all performed in triplicate. Tuberculosis quantitative viability microscopy predicted quantitative culture results such that 76% of results agreed within ±1 logarithm (rS=0.85; P<.0001). In 31 patients with non-multidrug-resistant (MDR) tuberculosis, viability and quantitative culture results approximately halved (both 0.27 log reduction, P<.001) daily. For patients with non-MDR tuberculosis and available data, by treatment day 9 there was a >10-fold reduction in viability in 100% (24/24) of cases and quantitative culture in 95% (19/20) of cases. Four other patients subsequently found to have MDR tuberculosis had no significant changes in viability (P=.4) or quantitative culture (P=.6) results during early treatment. The change in viability and quantitative culture results during early treatment differed significantly between patients with non-MDR tuberculosis and those with MDR tuberculosis (both P<.001). Acid-fast microscopy results changed little during early treatment, and this change was similar for non-MDR tuberculosis vs MDR tuberculosis (P=.6). Tuberculosis quantitative viability microscopy is a simple test that within 1 hour predicted quantitative culture results that became available weeks later, rapidly indicating whether patients were responding to tuberculosis therapy. © The Author 2014. Published by Oxford University Press on behalf of

  8. Chronic Cluster Headache with an Atypical Presentation and Treatment Response

    PubMed Central

    Morais, Hugo

    2016-01-01

    The management of cluster headache (CH) may be challenging. We report a 50-year-old male with recurrent attacks of dull and severe unilateral periorbital pain, lasting 30–45 minutes, twice a day, exclusively during sleep, and accompanied by ipsilateral rhinorrhea and lacrimation. The pain switched sides within every attack. CH treatment was initiated but the patient maintained recurrence rates compatible with chronic CH, even after increasing verapamil to 460 mg/day. Afterwards we decided to add lithium (800 mg/day). With this treatment the severity and recurrence of CH substantially decreased, despite the patient's autonomous decision to take lithium only during the acute phase of the cluster. The exclusively alternating location and the excellent response to short cycles of lithium represent two unique features of CH. PMID:28127484

  9. Transcriptomic Response to Nitric Oxide Treatment in Larix olgensis Henry

    PubMed Central

    Hu, Xiaoqing; Yang, Jingli; Li, Chenghao

    2015-01-01

    Larix olgensis Henry is an important coniferous species found in plantation forests in northeastern China, but it is vulnerable to pathogens. Nitric oxide (NO) is an important molecule involved in plant resistance to pathogens. To study the regulatory role of NO at the transcriptional level, we characterized the transcriptomic response of L. olgensis seedlings to sodium nitroprusside (SNP, NO donor) using Illumina sequencing and de novo transcriptome assembly. A significant number of putative metabolic pathways and functions associated with the unique sequences were identified. Genes related to plant pathogen infection (FLS2, WRKY33, MAPKKK, and PR1) were upregulated with SNP treatment. This report describes the potential contribution of NO to disease resistance in L. olgensis as induced by biotic stress. Our results provide a substantial contribution to the genomic and transcriptomic resources for L. olgensis, as well as expanding our understanding of the involvement of NO in defense responses at the transcriptional level. PMID:26633380

  10. Understanding the neuroinflammatory response following concussion to develop treatment strategies

    PubMed Central

    Patterson, Zachary R.; Holahan, Matthew R.

    2012-01-01

    Mild traumatic brain injuries (mTBI) have been associated with long-term cognitive deficits relating to trauma-induced neurodegeneration. These long-term deficits include impaired memory and attention, changes in executive function, emotional instability, and sensorimotor deficits. Furthermore, individuals with concussions show a high co-morbidity with a host of psychiatric illnesses (e.g., depression, anxiety, addiction) and dementia. The neurological damage seen in mTBI patients is the result of the impact forces and mechanical injury, followed by a delayed neuroimmune response that can last hours, days, and even months after the injury. As part of the neuroimmune response, a cascade of pro- and anti-inflammatory cytokines are released and can be detected at the site of injury as well as subcortical, and often contralateral, regions. It has been suggested that the delayed neuroinflammatory response to concussions is more damaging then the initial impact itself. However, evidence exists for favorable consequences of cytokine production following traumatic brain injuries as well. In some cases, treatments that reduce the inflammatory response will also hinder the brain's intrinsic repair mechanisms. At present, there is no evidence-based pharmacological treatment for concussions in humans. The ability to treat concussions with drug therapy requires an in-depth understanding of the pathophysiological and neuroinflammatory changes that accompany concussive injuries. The use of neurotrophic factors [e.g., nerve growth factor (NGF)] and anti-inflammatory agents as an adjunct for the management of post-concussion symptomology will be explored in this review. PMID:23248582

  11. Time to treatment response in first episode schizophrenia: should acute treatment trials last several months?

    PubMed Central

    Gallego, Juan A.; Robinson, Delbert G.; Sevy, Serge M.; Napolitano, Barbara; McCormack, Joanne; Lesser, Martin L.; Kane, John M.

    2010-01-01

    Objectives Response patterns may differ between patients with first episode and multi-episode schizophrenia. This analysis explored trial duration with first episode patients and whether early limited improvement predicts ultimate lack of treatment response with first episode patients as it does with multi-episode patients. Methods 112 subjects (mean age=23.3 years [SD=5.1]) who presented between November 1998 and October 2004 with a first episode of psychosis and had a DSM-IV diagnosis of schizophrenia, schizophreniform or schizoaffective disorder, were randomly assigned to treatment with olanzapine or risperidone for 16 weeks. Treatment response, the primary outcome measure, was defined as a rating of mild or better on all of the positive symptom items on the SADS-C + PD. Response rates were calculated for each study week. A logistic regression analysis examined the association between percent reduction in symptom severity scores from baseline values at weeks 2, 4 or 8 and response by week 16. Results The estimated cumulative response rate by week 8 was 39.59% (95% CI: 29.77% – 49.41%) and 65.19% (95% CI: 55.11% – 75.27%) by week 16. The confidence intervals for estimated response at weeks 10, 12, 14 and 16 were not distinct. Response rates increased approximately 5 to 6 percentage points each 2 week interval between week 10 and 16. Percent reduction in symptom severity score at week 4 (but not 2 or 8) was associated (Chi-square = 3.96; df = 1, p<0.05) with responder status at week 16 (odds ratio: 1.03; 95% CI: 1.00;1.05). However, receiver operating characteristic curves did not suggest any level of percent symptom reduction that would be clinically useful as a predictor of response by week 16. Conclusions Many first episode patients respond between weeks 8 and 16 of treatment with a single antipsychotic medication. Limited early symptom improvement does not identify with enough accuracy to be clinically useful those first episode patients who will not

  12. Mycobacteria-specific cytokine responses as correlates of treatment response in active and latent tuberculosis.

    PubMed

    Clifford, Vanessa; Tebruegge, Marc; Zufferey, Christel; Germano, Susie; Forbes, Ben; Cosentino, Lucy; McBryde, Emma; Eisen, Damon; Robins-Browne, Roy; Street, Alan; Denholm, Justin; Curtis, Nigel

    2017-08-01

    A biomarker indicating successful tuberculosis (TB) therapy would assist in determining appropriate length of treatment. This study aimed to determine changes in mycobacteria-specific antigen-induced cytokine biomarkers in patients receiving therapy for latent or active TB, to identify biomarkers potentially correlating with treatment success. A total of 33 adults with active TB and 36 with latent TB were followed longitudinally over therapy. Whole blood stimulation assays using mycobacteria-specific antigens (CFP-10, ESAT-6, PPD) were done on samples obtained at 0, 1, 3, 6 and 9 months. Cytokine responses (IFN-γ, IL-1ra, IL-2, IL-10, IL-13, IP-10, MIP-1β, and TNF-α) in supernatants were measured by Luminex xMAP immunoassay. In active TB cases, median IL-1ra (with CFP-10 and with PPD stimulation), IP-10 (CFP-10, ESAT-6), MIP-1β (ESAT-6, PPD), and TNF-α (ESAT-6) responses declined significantly over the course of therapy. In latent TB cases, median IL-1ra (CFP-10, ESAT-6, PPD), IL-2 (CFP-10, ESAT-6), and IP-10 (CFP-10, ESAT-6) responses declined significantly. Mycobacteria-specific cytokine responses change significantly over the course of therapy, and their kinetics in active TB differ from those observed in latent TB. In particular, mycobacteria-specific IL-1ra responses are potential correlates of successful therapy in both active and latent TB. Copyright © 2017 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

  13. Hepatic gene expression during treatment with peginterferon and ribavirin: Identifying molecular pathways for treatment response.

    PubMed

    Feld, Jordan J; Nanda, Santosh; Huang, Ying; Chen, Weiping; Cam, Maggie; Pusek, Susan N; Schweigler, Lisa M; Theodore, Dickens; Zacks, Steven L; Liang, T Jake; Fried, Michael W

    2007-11-01

    The reasons for hepatitis C treatment failure remain unknown but may be related to different host responses to therapy. In this study, we compared hepatic gene expression in patients prior to and during peginterferon and ribavirin therapy. In the on-treatment group, patients received either ribavirin for 72 hours prior to peginterferon alpha-2a injection or peginterferon alpha-2a for 24 hours, prior to biopsy. The patients were grouped into rapid responders (RRs) with a greater than 2-log drop and slow responders (SRs) with a less than 2-log drop in hepatitis C virus RNA by week 4. Pretreatment biopsy specimens were obtained from a matched control group. The pretreatment patients were grouped as RRs or SRs on the basis of the subsequent treatment response. Gene expression profiling was performed with Affymetrix microarray technology. Known interferon-stimulated genes (ISGs) were induced in treated patients. In the pretreatment group, future SRs had higher pretreatment ISG expression than RRs. On treatment, RRs and SRs had similar absolute ISG expression, but when it was corrected for the baseline expression with the pretreatment group, RRs showed a greater fold change in ISGs, whereas SRs showed a greater change in interferon (IFN)-inhibitory pathways. The patients pretreated with ribavirin had heightened induction of IFN-related genes and down-regulation of genes involved in IFN inhibition and hepatic stellate cell activation. These data suggest that ISG inducibility is important for the treatment response and that ribavirin may improve outcomes by enhancing hepatic gene responses to peginterferon. Collectively, these mechanisms may provide a molecular basis for the improved efficacy of combination therapy.

  14. Rapid acid treatment of Escherichia coli: transcriptomic response and recovery

    PubMed Central

    Kannan, Geetha; Wilks, Jessica C; Fitzgerald, Devon M; Jones, Brian D; BonDurant, Sandra S; Slonczewski, Joan L

    2008-01-01

    Background Many E. coli genes show pH-dependent expression during logarithmic growth in acid (pH 5–6) or in base (pH 8–9). The effect of rapid pH change, however, has rarely been tested. Rapid acid treatment could distinguish between genes responding to external pH, and genes responding to cytoplasmic acidification, which occurs transiently following rapid external acidification. It could reveal previously unknown acid-stress genes whose effects are transient, as well as show which acid-stress genes have a delayed response. Results Microarray hybridization was employed to observe the global gene expression of E. coli K-12 W3110 following rapid acidification of the external medium, from pH 7.6 to pH 5.5. Fluorimetric observation of pH-dependent tetR-YFP showed that rapid external acidification led to a half-unit drop in cytoplasmic pH (from pH 7.6 to pH 6.4) which began to recover within 20 s. Following acid treatment, 630 genes were up-regulated and 586 genes were down-regulated. Up-regulated genes included amino-acid decarboxylases (cadA, adiY, gadA), succinate dehydrogenase (sdhABCD), biofilm-associated genes (bdm, gatAB, and ymgABC), and the Gad, Fur and Rcs regulons. Genes with response patterns consistent with cytoplasmic acid stress were revealed by addition of benzoate, a membrane-permeant acid that permanently depresses cytoplasmic pH without affecting external pH. Several genes (yagU, ygiN, yjeI, and yneI) were up-regulated specifically by external acidification, while other genes (fimB, ygaC, yhcN, yhjX, ymgABC, yodA) presented a benzoate response consistent with cytoplasmic pH stress. Other genes (the nuo operon for NADH dehydrogenase I, and the HslUV protease) showed delayed up-regulation by acid, with expression rising by 10 min following the acid shift. Conclusion Transcriptomic profiling of E. coli K-12 distinguished three different classes of change in gene expression following rapid acid treatment: up-regulation with or without recovery, and

  15. Gastric carcinoma: imaging diagnosis, staging and assessment of treatment response

    PubMed Central

    Hallinan, James Thomas Patrick Decourcy

    2013-01-01

    Abstract Gastric carcinoma (GC) is one of the most common causes of cancer-related death worldwide. Surgical resection is the only cure available and is dependent on the GC stage at presentation, which incorporates depth of tumor invasion, extent of lymph node and distant metastases. Accurate preoperative staging is therefore essential for optimal surgical management with consideration of preoperative and/or postoperative chemotherapy. Multidetector computed tomography (MDCT) with its ability to assess tumor depth, nodal disease and metastases is the preferred technique for staging GC. Endoscopic ultrasonography is more accurate for assessing the depth of wall invasion in early cancer, but is limited in the assessment of advanced local or stenotic cancer and detection of distant metastases. Magnetic resonance imaging (MRI), although useful for staging, is not proven to be effective. Positron emission tomography (PET) is most useful for detecting and characterizing distant metastases. Both MDCT and PET are useful for assessment of treatment response following preoperative chemotherapy and for detection of recurrence after surgical resection. This review article discusses the usefulness of imaging modalities for detecting, staging and assessing treatment response for GC and the potential role of newer applications including CT volumetry, virtual gastroscopy and perfusion CT in the management of GC. PMID:23722535

  16. Pre-treatment high-resolution rectal MRI and treatment response to neoadjuvant chemoradiation

    PubMed Central

    Chang, George J.; You, Y. Nancy; Park, In Ja; Kaur, Harmeet; Hu, Chung-Yuan; Rodriguez-Bigas, Miguel A.; Skibber, John M.; Ernst, Randy D.

    2012-01-01

    Background Use of rectal MRI evaluation of patients with rectal cancer for primary tumor staging and for identification for poor prognostic features is increasing. MR imaging permits precise delineation of tumor anatomy and assessment of mesorectal tumor penetration and radial margin risk. Objective To evaluate the ability of pre-treatment rectal MRI to classify tumor response to neoadjuvant chemoradiation. Design Retrospective, consecutive cohort study, central review. Setting Tertiary academic hospital. Patients 62 consecutive patients with locally advanced (stage cII-cIII)rectal cancer who underwent rectal cancer protocol high resolution MRI prior to surgery(12/09-3/11). Main Outcome Measures Probability of good (ypT0-2N0) vs. poor (≥ypT3N0) response as a function of mesorectal tumor depth, lymph node status, extramural vascular invasion, and grade assessed by uni- and multi-variate logistic regression. Results Tumor response was good in 25, 40.3% and poor in 37, 59.7%.Median interval from MRI to OP was 7.9weeks (IQR: 7.0–9.0). MRI tumor depth was <1 mm in 10 (16.9%), 1–5 mm in 30 (50.8%), and >5 mm in 21(33.9%). LN status was positive in 40 (61.5%) and vascular invasion was present in 16 (25.8%). Tumor response was associated with MRI tumor depth (P=0.001), MRI lymph nodes status (P=<0.001)and vascular invasion (P=0.009). Multivariate regression indicated >5mm MRI tumor depth (OR=0.08, 95% CI=0.01–0.93, p=0.04) and MRI LN positivity (OR=0.12, 95% CI=0.03–0.53, p=0.005) were less likely to achieve a good response to neoadjuvant chemoradiotherapy. Limitations Uncertain generalizability in centers with limited experience with MRI staging for rectal cancer. Conclusion MRI assessment of tumor depth and lymph node status in rectal cancer is associated to tumor response to neoadjuvant chemoradiotherapy. These factors should therefore be considered for stratification of patients for novel treatment strategies reliant on pathologic response to treatment or for

  17. Predicting Treatment Response for Oppositional Defiant and Conduct Disorder Using Pre-treatment Adrenal and Gonadal Hormones.

    PubMed

    Shenk, Chad E; Dorn, Lorah D; Kolko, David J; Susman, Elizabeth J; Noll, Jennie G; Bukstein, Oscar G

    2012-12-01

    Variations in adrenal and gonadal hormone profiles have been linked to increased rates of oppositional defiant disorder (ODD) and conduct disorder (CD). These relationships suggest that certain hormone profiles may be related to how well children respond to psychological treatments for ODD and CD. The current study assessed whether pre-treatment profiles of adrenal and gonadal hormones predicted response to psychological treatment of ODD and CD. One hundred five children, 6 - 11 years old, participating in a randomized, clinical trial provided samples for cortisol, testosterone, dehydroepiandrosterone, and androstenedione. Diagnostic interviews of ODD and CD were administered up to three years post-treatment to track treatment response. Group-based trajectory modeling identified two trajectories of treatment response: 1) a High-response trajectory where children demonstrated lower rates of an ODD or CD diagnosis throughout follow-up, and 2) a Low-response trajectory where children demonstrated higher rates of an ODD or CD diagnosis throughout follow-up. Hierarchical logistic regression predicting treatment response demonstrated that children with higher pre-treatment concentrations of testosterone were four times more likely to be in the Low-response trajectory. No other significant relationship existed between pre-treatment hormone profiles and treatment response. These results suggest that higher concentrations of testosterone are related to how well children diagnosed with ODD or CD respond to psychological treatment over the course of three years.

  18. [Exposure to addictogenic substances, conditioned response and treatment of the exposure with response prevention].

    PubMed

    Khazaal, Y; Frésard, E; Zullino, D

    2007-01-01

    Exposure to drugs or related cues is associated with psycho-physiological reactivity. These responses are conditioned during periods of active consumption. Exposure with response prevention (EPR) is a treatment established for anxiety disorder and aims to reduce anxiety by an extinction of previously conditioned responses. The conditioning recognized in additive processes has led to research into EPR's therapeutic potential for treating addiction. This paper is a review of the main studies on reactivity to cues, and EPR, particularly with respect to addiction to alcohol, opiates, cocaine and tobacco. This review is based on information from the Medline database, dealing with cue reactivity, attentional bias during exposure to cues and exposure treatment for addiction in general and, in particular, for each of the aforementioned substances. Exposure to drug-related cues is clearly associated with psycho-physiological reactivity and with attentional bias. Those phenomena are associated with craving and more difficulty in maintaining abstinence. The subject's attention is thus held by a large number of drug-related environmental stimuli. These observations are linked with conditioning phenomena and suggest the possibility of treatment by EPR conditioning extinction procedures. EPR has been most widely studied for abuse and alcohol addiction. Case reports give favourable outcomes. Results from controlled studies are less clear. Studies on patients addicted to cocaine or heroine are still limited and not conclusive. Different controlled studies on EPR for nicotine addiction have not produced conclusions in favour of this treatment. Generally, the EPR procedures used vary among studies. Studies focussing particularly on the evolution of physiological responses in a laboratory setting after EPR have demonstrated reduced autonomic nervous system activity. These results do not consistently lead to a reduction in consumption behaviour and in craving when the patient is in

  19. Clinical neuroimaging markers of response to treatment in mood disorders.

    PubMed

    Porcu, Michele; Balestrieri, Antonella; Siotto, Paolo; Lucatelli, Pierleone; Anzidei, Michele; Suri, Jasjit S; Zaccagna, Fulvio; Argiolas, Giovanni Maria; Saba, Luca

    2016-10-11

    Mood disorders (MD) are important and frequent psychiatric pathologies, and the management of the patients affected by thes conditions represent an important factor of disability and a huge problem in socialterms and an economic burden. The "in-vivo" studies can help researchers to understand the first events at the base of the development of the pathology and to identify the molecular and non-molecular targets of therapies, but theyhave strong limitations due to the fact that human brain circuitsthem selvesare difficult to be reproduced in animal models. Besides these challenges, they are difficult to be selectively studied with the modern imaging (such as Magnetic Resonance and Positron Emitted Tomography/Computed Tomography) and non-imaging (such as electroencephalography, magnetoencephalography, transcranial magnetic stimulation and evoked potentials) methods. In comparison with other methods, the "in-vivo" imaging investigations have higher temporal and spatial resolution compared to the "in-vivo" non-imaging techniques.All these factors make difficult to fully understand the aetiology and pathophysiology of these disorders, and consequently make difficult not only in the development, but also the monitoring of the actions of therapies,which according to clinical observations have been demonstrated effective in the treatment. In this review, we will focus our attention on the actual state-of-theart of role of imaging in monitoring of treatment of MD, underlying that up to date there are still not standardized imaging markers available in clinical practice.We will analyse briefly the actual classification of MD; then we will focus on the "in vivo" imaging modalities used in research and clinical activity, the current knowledge about the neural models at the base ofMD. Finally the last part of the review focuses on analysis of the principle markers of response to the treatment according to the type of treatment used and to the imaging techniques adopted.

  20. Proteomic Response to Acupuncture Treatment in Spontaneously Hypertensive Rats

    PubMed Central

    Nabar, Neel R.; Pan, Sanqiang; Tang, Chunzhi; Huang, Yong; Hao, Mufeng; Yang, Zhonghua; Ma, Chunmei; Zhang, Jin; Chew, Helen; He, Zhenquan; Yang, Junjun; Su, Baogui; Zhang, Jian; Liang, Jun; Sneed, Kevin B.; Zhou, Shu-Feng

    2012-01-01

    Previous animal and clinical studies have shown that acupuncture is an effective alternative treatment in the management of hypertension, but the mechanism is unclear. This study investigated the proteomic response in the nervous system to treatment at the Taichong (LR3) acupoint in spontaneously hypertensive rats (SHRs). Unanesthetized rats were subject to 5-min daily acupuncture treatment for 7 days. Blood pressure was monitored over 7 days. After euthanasia on the 7th day, rat medullas were dissected, homogenized, and subject to 2D gel electrophoresis and MALDI-TOF analysis. The results indicate that blood pressure stabilized after the 5th day of acupuncture, and compared with non-acupoint treatment, Taichong-acupunctured rat’s systolic pressure was reduced significantly (P<0.01), though not enough to bring blood pressure down to normal levels. The different treatment groups also showed differential protein expression: the 2D images revealed 571±15 proteins in normal SD rats’ medulla, 576±31 proteins in SHR’s medulla, 597±44 proteins in medulla of SHR after acupuncturing Taichong, and 616±18 proteins in medulla of SHR after acupuncturing non-acupoint. In the medulla of Taichong group, compared with non-acupoint group, seven proteins were down-regulated: heat shock protein-90, synapsin-1, pyruvate kinase isozyme, NAD-dependent deacetylase sirtuin-2, protein kinase C inhibitor protein 1, ubiquitin hydrolase isozyme L1, and myelin basic protein. Six proteins were up-regulated: glutamate dehydrogenase 1, aldehyde dehydrogenase 2, glutathione S-transferase M5, Rho GDP dissociation inhibitor 1, DJ-1 protein and superoxide dismutase. The altered expression of several proteins by acupuncture has been confirmed by ELISA, Western blot and qRT-PCR assays. The results indicate an increase in antioxidant enzymes in the medulla of the SHRs subject to acupuncture, which may provide partial explanation for the antihypertensive effect of acupuncture. Further studies

  1. Proteomic response to acupuncture treatment in spontaneously hypertensive rats.

    PubMed

    Lai, Xinsheng; Wang, Jiayou; Nabar, Neel R; Pan, Sanqiang; Tang, Chunzhi; Huang, Yong; Hao, Mufeng; Yang, Zhonghua; Ma, Chunmei; Zhang, Jin; Chew, Helen; He, Zhenquan; Yang, Junjun; Su, Baogui; Zhang, Jian; Liang, Jun; Sneed, Kevin B; Zhou, Shu-Feng

    2012-01-01

    Previous animal and clinical studies have shown that acupuncture is an effective alternative treatment in the management of hypertension, but the mechanism is unclear. This study investigated the proteomic response in the nervous system to treatment at the Taichong (LR3) acupoint in spontaneously hypertensive rats (SHRs). Unanesthetized rats were subject to 5-min daily acupuncture treatment for 7 days. Blood pressure was monitored over 7 days. After euthanasia on the 7(th) day, rat medullas were dissected, homogenized, and subject to 2D gel electrophoresis and MALDI-TOF analysis. The results indicate that blood pressure stabilized after the 5th day of acupuncture, and compared with non-acupoint treatment, Taichong-acupunctured rat's systolic pressure was reduced significantly (P<0.01), though not enough to bring blood pressure down to normal levels. The different treatment groups also showed differential protein expression: the 2D images revealed 571 ± 15 proteins in normal SD rats' medulla, 576 ± 31 proteins in SHR's medulla, 597 ± 44 proteins in medulla of SHR after acupuncturing Taichong, and 616 ± 18 proteins in medulla of SHR after acupuncturing non-acupoint. In the medulla of Taichong group, compared with non-acupoint group, seven proteins were down-regulated: heat shock protein-90, synapsin-1, pyruvate kinase isozyme, NAD-dependent deacetylase sirtuin-2, protein kinase C inhibitor protein 1, ubiquitin hydrolase isozyme L1, and myelin basic protein. Six proteins were up-regulated: glutamate dehydrogenase 1, aldehyde dehydrogenase 2, glutathione S-transferase M5, Rho GDP dissociation inhibitor 1, DJ-1 protein and superoxide dismutase. The altered expression of several proteins by acupuncture has been confirmed by ELISA, Western blot and qRT-PCR assays. The results indicate an increase in antioxidant enzymes in the medulla of the SHRs subject to acupuncture, which may provide partial explanation for the antihypertensive effect of acupuncture. Further

  2. Trichotillomania: a good response to treatment with N-acetylcysteine*

    PubMed Central

    Barroso, Livia Ariane Lopes; Sternberg, Flavia; Souza, Maria Natalia Inacio de Fraia e; Nunes, Gisele Jacobino de Barros

    2017-01-01

    Trichotillomania is considered a behavioral disorder and is characterized by the recurring habit of pulling one's hair, resulting in secondary alopecia. It affects 1% of the adult population, and 2 to 4.4% of psychiatric patients meet the diagnostic criteria. It can occur at any age and is more prevalent in adolescents and females. Its occurrence in childhood is not uncommon and tends to have a more favorable clinical course. The scalp, eyebrows and eyelashes are the most commonly affected sites. Glutamate modulating agents, such as N-acetylcysteine, have been shown to be a promising treatment. N-acetylcysteine acts by reducing oxidative stress and normalizing glutaminergic transmission. In this paper, we report a case of trichotillomania with an excellent response to N-acetylcysteine.

  3. Factors Affecting Response to Infertility Treatment: Case of Iran

    PubMed Central

    Peyromusavi, Fatemeh; Barouni, Mohsen; Naderi, Tayebeh; Shahravan, Arash

    2016-01-01

    Introduction: Infertility affects both women and men in all the countries. Infertility often has profound long-term or short-term impacts on the people involved and puts them at risk of familial and social pressures. According to WHO estimates, between 8% and 12% of all the couples worldwide experience some form of infertility during their reproductive life, i.e. 50–80 million people are affected. The aim of this study was to evaluate the response to infertility treatment by taking into account factors such as age, hirsutism, menstruation and galactose among women in Kerman. Methodology: Of a total of 300 patient files evaluated 220 cases were flawless, of which the study factors were recorded. These data were estimated by Logit model. The dependent variable was the response to treatment (0 and 1) and the independent variables included age of men and women, hirsutism, menstruation, galactose, duration of the period no preventive measures were used and body mass index. After entering the data, model output was analyzed by using the STATA software. Results: The results showed that of all the model variables, female age (prob=0.0065), menstruation (prob=0.04), hirsutism (prob=0.02), marriage age (in months) (prob=0.02) and BMI were significant and other variables were not significant. McFadden analysis for goodness of fit was 0.92. Conclusion: The study results showed that women should pay more attention to variables such as BMI, menstruation quality (regular and irregular) and aging because clinical disregard of any of the above can have a significant impact on the individual’s fertility. PMID:26234994

  4. Evidence-Responsiveness and the Ongoing Autonomy of Treatment Preferences.

    PubMed

    Weimer, Steven

    2017-06-14

    To be an autonomous agent is to determine one's own path in life. However, this cannot plausibly be seen as a one-off affair. An autonomous agent does not merely set herself on a particular course and then lock the steering wheel in place, so to speak, but must maintain some form of ongoing control over her direction in life-must keep her eyes on the road and her hands on the wheel. Circumstances often change in important and unexpected ways, after all, and it is reasonable to think that a crucial part of autonomy consists of the ability and disposition to recognize and properly respond to such changes. This implies, I contend, that a patient whose initial decision to undergo a given treatment satisfied plausible requirements of autonomy, but who is now unable to recognize that available evidence indicates the need to reconsider her medical situation and options has come to lack autonomy with respect to her desire to continue that treatment. However, and despite its importance with respect to both theoretical understandings of autonomy and applications of the concept to clinical ethics, this ongoing aspect of autonomy has received little attention. This paper aims to go some way toward remedying that. I first critically review two of the few theories of autonomy that do address "evidence-responsiveness" so as to identify and elaborate what I take to be the most promising way in which to account for this aspect of autonomy. After considering and responding to a possible objection to the evidence-responsiveness condition I propose, I conclude by discussing its clinical implications. That condition, I argue, is not merely theoretically sound, but can and should be applied to clinical practice.

  5. [Emotional responsiveness of substance abusers under outpatient treatment].

    PubMed

    Chicharro, Juan; Pérez-García, Ana M; Sanjuán, Pilar

    2012-01-01

    The emotions predispose to action providing information from both internal and external environment. There is evidence indicating that the emotional response in drugdependent patients is different from that of the not consuming population. The present work analyzed the emotions of drugdependent under ambulatory treatment (N=57), following the Lang's theory of emotion, considering the dimensions of valence, arousal and dominance or control, across the International Affective Picture System (IAPS), individually applied. The results were contrasted with a control group of not consuming persons (N=44) of similar age, since this variable concerns emotional experience. The influence of sex was also analyzed, considering the possible differences between men and women in emotional experience. The results can be summarized in the following points: (1) There were significant differences between substance abusers and not consumers in the dimension of valence, valuing the consumers the emotional stimuli of the most extreme form (the agreeable ones as better, and the disagreeable ones as worse); (2) there were no differences between both groups in the arousal and dominance dimensions; and (3) women reported more arousal before aversive images, and less before the sexual ones, than males, independently of they were or not substance abusers. Finally, it is suggested the need to deep into the analysis of sex differences and into the images selected, as well as into the usefulness of the emotion centred therapies for the treatment of drugdependency.

  6. Breaking the DNA damage response to improve cervical cancer treatment.

    PubMed

    Wieringa, Hylke W; van der Zee, Ate G J; de Vries, Elisabeth G E; van Vugt, Marcel A T M

    2016-01-01

    Every year, cervical cancer affects ∼500,000 women worldwide, and ∼275,000 patients die of this disease. The addition of platin-based chemotherapy to primary radiotherapy has increased 5-year survival of advanced-stage cervical cancer patients, which is, however, still only 66%. One of the factors thought to contribute to treatment failure is the ability of tumor cells to repair chemoradiotherapy-induced DNA damage. Therefore, sensitization of tumor cells for chemoradiotherapy via inhibition of the DNA damage response (DDR) as a novel strategy to improve therapy effect, is currently studied pre-clinically as well as in the clinic. Almost invariably, cervical carcinogenesis involves infection with the human papillomavirus (HPV), which inactivates part of the DNA damage response. This HPV-mediated partial inactivation of the DDR presents therapeutic targeting of the residual DDR as an interesting approach to achieve chemoradio-sensitization for cervical cancer. How the DDR can be most efficiently targeted, however, remains unclear. The fact that cisplatin and radiotherapy activate multiple signaling axes within the DDR further complicates a rational choice of therapeutic targets within the DDR. In this review, we provide an overview of the current preclinical and clinical knowledge about targeting the DDR in cervical cancer.

  7. MicroRNAs, DNA Damage Response, and Cancer Treatment

    PubMed Central

    He, Mingyang; Zhou, Weiwei; Li, Chuang; Guo, Mingxiong

    2016-01-01

    As a result of various stresses, lesions caused by DNA-damaging agents occur constantly in each cell of the human body. Generally, DNA damage is recognized and repaired by the DNA damage response (DDR) machinery, and the cells survive. When repair fails, the genomic integrity of the cell is disrupted—a hallmark of cancer. In addition, the DDR plays a dual role in cancer development and therapy. Cancer radiotherapy and chemotherapy are designed to eliminate cancer cells by inducing DNA damage, which in turn can promote tumorigenesis. Over the past two decades, an increasing number of microRNAs (miRNAs), small noncoding RNAs, have been identified as participating in the processes regulating tumorigenesis and responses to cancer treatment with radiation therapy or genotoxic chemotherapies, by modulating the DDR. The purpose of this review is to summarize the recent findings on how miRNAs regulate the DDR and discuss the therapeutic functions of miRNAs in cancer in the context of DDR regulation. PMID:27973455

  8. Helicobacter pylori Infection in Children. Antimicrobial Resistance and Treatment Response.

    PubMed

    Montes, Milagrosa; Villalon, Flor N; Eizaguirre, Francisco J; Delgado, Maider; Muñoz-Seca, Ignacio M; Fernández-Reyes, María; Pérez-Trallero, Emilio

    2015-06-01

    The aim of this study was to determine the appropriateness of the recent recommendations for managing Helicobacter pylori infection in children in a university hospital in Southern Europe. Antimicrobial resistance and response to eradication therapy were also determined. The presence of H. pylori was studied in 143 children: by gastric biopsy culture (GBC), (13)C-urea breath test (UBT) and stool antigen immunochromatography test (SAIT) in 56 children; by GBC and UBT in 20, by GBC and SAIT in 18, and by GBC alone in 49. Antimicrobial susceptibility was determined by E-test. Infection was defined as a positive culture or positivity in both UBT and SAIT. Disease progression was studied in 118 patients. First evaluation of symptoms was carried out at 3-6 months after diagnosis and/or after treatment of the infection. H. pylori was detected in 74 from the 143 children analyzed (100% GBC positive, 98.1% UBT positive, and 58.1% SAIT positive). The main symptom was chronic abdominal pain (n = 121). Macroscopic antral nodularity was observed in 29.7% of infected patients and in 5.8% of uninfected patients, respectively. Resistance to clarithromycin and metronidazole was found in 34.7 and 16.7%, respectively. Eradication when susceptible antimicrobials were used occurred in 78.7% (48/61) versus 37.5% (3/8) when the treatment included a drug with resistance (p = .024). In patients with recurrent abdominal pain, symptoms resolved in 92.9% (39/42) patients with HP eradication versus 42.9% (6/14) without HP eradication (p < .001). Treated patients often failed to meet the criteria established in the guidelines for H. pylori diagnostic screening and treatment because most of them had only recurrent abdominal pain, but remission of their symptoms was associated with H. pylori eradication. © 2014 John Wiley & Sons Ltd.

  9. Lung cancer treatment costs, including patient responsibility, by disease stage and treatment modality, 1992 to 2003.

    PubMed

    Cipriano, Lauren E; Romanus, Dorothy; Earle, Craig C; Neville, Bridget A; Halpern, Elkan F; Gazelle, G Scott; McMahon, Pamela M

    2011-01-01

    The objective of this analysis was to estimate costs for lung cancer care and evaluate trends in the share of treatment costs that are the responsibility of Medicare beneficiaries. The Surveillance, Epidemiology, and End Results (SEER)-Medicare data from 1991-2003 for 60,231 patients with lung cancer were used to estimate monthly and patient-liability costs for clinical phases of lung cancer (prediagnosis, staging, initial, continuing, and terminal), stratified by treatment, stage, and non-small- versus small-cell lung cancer. Lung cancer-attributable costs were estimated by subtracting each patient's own prediagnosis costs. Costs were estimated as the sum of Medicare reimbursements (payments from Medicare to the service provider), co-insurance reimbursements, and patient-liability costs (deductibles and "co-payments" that are the patient's responsibility). Costs and patient-liability costs were fit with regression models to compare trends by calendar year, adjusting for age at diagnosis. The monthly treatment costs for a 72-year-old patient, diagnosed with lung cancer in 2000, in the first 6 months ranged from $2687 (no active treatment) to $9360 (chemo-radiotherapy); costs varied by stage at diagnosis and histologic type. Patient liability represented up to 21.6% of care costs and increased over the period 1992-2003 for most stage and treatment categories, even when care costs decreased or remained unchanged. The greatest monthly patient liability was incurred by chemo-radiotherapy patients, which ranged from $1617 to $2004 per month across cancer stages. Costs for lung cancer care are substantial, and Medicare is paying a smaller proportion of the total cost over time. Copyright © 2011 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

  10. Neurocognitive predictors of treatment response to randomized treatment in adults with tic disorders.

    PubMed

    Abramovitch, Amitai; Hallion, Lauren S; Reese, Hannah E; Woods, Douglas W; Peterson, Alan; Walkup, John T; Piacentini, John; Scahill, Lawrence; Deckersbach, Thilo; Wilhelm, Sabine

    2017-03-06

    Tourette's disorder (TS) and chronic tic disorder (CTD) are neurodevelopmental disorders characterized by involuntary vocal and motor tics. Consequently, TS/CTD have been conceptualized as disorders of cognitive and motor inhibitory control. However, most neurocognitive studies have found comparable or superior inhibitory capacity among individuals with TS/CTD relative to healthy controls. These findings have led to the hypothesis that individuals with TS/CTD develop increased inhibitory control due to the constant need to inhibit tics. However, the role of cognitive control in TS/CTD is not yet understood, particularly in adults. To examine the role of inhibitory control in TS/CTD, the present study investigated this association by assessing the relationship between inhibitory control and treatment response in a large sample of adults with TS/CTD. As part of a large randomized trial comparing behavior therapy versus supportive psychotherapy for TS/CTD, a battery of tests, including tests of inhibitory control was administered to 122 adults with TS/CTD at baseline. We assessed the association between neuropsychological test performance and change in symptom severity, as well as compared the performance of treatment responders and non-responders as defined by the Clinical Global Impression Scale. Results indicated that change in symptoms, and treatment response were not associated with neuropsychological performance on tests of inhibitory control, intellectual ability, or motor function, regardless of type of treatment. The finding that significant change in symptom severity of TS/CTD patients is not associated with impairment or change in inhibitory control regardless of treatment type suggests that inhibitory control may not be a clinically relevant facet of these disorders in adults.

  11. Different functioning of prefrontal cortex predicts treatment response after a selective serotonin reuptake inhibitor treatment in patients with major depression.

    PubMed

    Masuda, Koji; Nakanishi, Mari; Okamoto, Kana; Kawashima, Chiwa; Oshita, Harumi; Inoue, Ayako; Takita, Fuku; Izumi, Toshihiko; Ishitobi, Yoshinobu; Higuma, Haruka; Kanehisa, Masayuki; Ninomiya, Taiga; Tanaka, Yoshinori; Akiyoshi, Jotaro

    2017-05-01

    Major depressive disorder (MDD) is often resistant to treatment with usual approaches. Patients with MDD have shown hypofunction of the frontotemporal cortex in verbal fluency test (VFT)-related near-infrared spectroscopy (NIRS). We examined whether the reactions to drug treatment in treatment-naive patients with MDD could be predicted by NIRS outcomes at the initial investigation. All subjects underwent psychological testing to determine levels of anxiety and depression. VFT was used to examine the functioning of the frontotemporal lobes. We administered selective serotonin reuptake inhibitors (SSRIs) for 12 weeks. Subjects included 28 patients with MDD with response to SSRIs (Response group), 19 with no response (Non-Response group), and 63 age-, sex-, and education years-matched healthy controls (HC). We found in the frontotemporal region that hemodynamic responses were significantly smaller in patients with Response and Non-Response groups than in HC before treatment. We also found in the medial frontal region that hemodynamic responses were significantly larger in patients with Response groups than in patients with Non-Response group before treatment. Patients with MDD scored significantly higher anxiety and depressive states than those in HC on several measures. The Response and Non-Response groups also had higher scores in future denial, threat prediction, self-denial, past denial, and interpersonal threat sections of Anxiety Cognition Scale (DACS). According to the stepwise regression analysis, one variable was determined as independent predictors of response: confusion (Post-POMS). The number of patients and healthy controls was relatively small, and we will increase the number of participants in future studies. NIRS has reduced spatial resolution, which confuses the identification of the measurement position when using NIRS alone. Cognitive vulnerabilities are associated with predictors of SSRI treatment response. Different hemodynamic activities in the

  12. Potential treatment options and future research to increase hepatitis C virus treatment response rate.

    PubMed

    Tencate, Veronica; Sainz, Bruno; Cotler, Scott J; Uprichard, Susan L

    2010-10-01

    Hepatitis C virus (HCV) is a liver-tropic blood-borne pathogen that affects more than 170 million people worldwide. Although acute infections are usually asymptomatic, up to 90% of HCV infections persist with the possibility of long-term consequences such as liver fibrosis, cirrhosis, steatosis, insulin resistance, or hepatocellular carcinoma. As such, HCV-associated liver disease is a major public health concern. Although the currently available standard of care therapy of pegylated interferon α plus ribavirin successfully treats infection in a subset of patients, the development of more effective, less toxic HCV antivirals is a health care imperative. This review not only discusses the limitations of the current HCV standard of care but also evaluates upcoming HCV treatment options and how current research elucidating the viral life cycle is facilitating the development of HCV-specific therapeutics that promise to greatly improve treatment response rates both before and after liver transplantation.

  13. Potential treatment options and future research to increase hepatitis C virus treatment response rate

    PubMed Central

    TenCate, Veronica; Sainz, Bruno; Cotler, Scott J; Uprichard, Susan L

    2010-01-01

    Hepatitis C virus (HCV) is a liver-tropic blood-borne pathogen that affects more than 170 million people worldwide. Although acute infections are usually asymptomatic, up to 90% of HCV infections persist with the possibility of long-term consequences such as liver fibrosis, cirrhosis, steatosis, insulin resistance, or hepatocellular carcinoma. As such, HCV-associated liver disease is a major public health concern. Although the currently available standard of care therapy of pegylated interferon α plus ribavirin successfully treats infection in a subset of patients, the development of more effective, less toxic HCV antivirals is a health care imperative. This review not only discusses the limitations of the current HCV standard of care but also evaluates upcoming HCV treatment options and how current research elucidating the viral life cycle is facilitating the development of HCV-specific therapeutics that promise to greatly improve treatment response rates both before and after liver transplantation. PMID:21331152

  14. Pathological complete response in neoadjuvant treatment of breast cancer.

    PubMed

    Cortazar, Patricia; Geyer, Charles E

    2015-05-01

    There has been recent interest in using pathological complete response (pCR) as a potential surrogate endpoint for long-term outcomes in the neoadjuvant treatment of high-risk, early-stage breast cancer. We review the clinical trials that have contributed to our understanding of the association between pCR and long-term outcomes, describe the various definitions of pCR, describe patient populations in which pCR may predict long-term benefit, and discuss the implications of pCR on drug development and accelerated approval for neoadjuvant treatment of breast cancer. Varying definitions of pCR across clinical trials conducted in heterogeneous patient populations make understanding the association of pCR with long-term outcomes challenging. The US Food and Drug Administration established the Collaborative Trials in Neoadjuvant Breast Cancer group to evaluate the potential use of pCR as a regulatory endpoint. The group demonstrated that pCR defined as no residual invasive cancer in the breast and axillary nodes with presence or absence of in situ cancer (ypT0/is ypN0 or ypT0 ypN0) provided a better association with improved outcomes compared to eradication of invasive tumor from the breast alone (ypT0/is). Even though pCR was not validated as a surrogate endpoint for long-term outcomes, the promising data regarding the strong association of pCR with substantially improved outcomes in individual patients with more aggressive subtypes of breast cancer supported the opening of an accelerated approval pathway for patients with high-risk, early-stage breast cancer.

  15. Transient CNS responses to repeated binge ethanol treatment

    PubMed Central

    Zahr, Natalie M; Rohlfing, Torsten; Mayer, Dirk; Luong, Richard; Sullivan, Edith V; Pfefferbaum, Adolf

    2016-01-01

    Adaptive changes occur in response to repeated exposure to drugs. Although ethanol (EtOH) is known to induce pharmacokinetic tolerance, the effects of EtOH on in vivo, magnetic resonance (MR)-detectable brain measures across repeated exposures have not previously been reported. Of 28 rats weighing 341±22g at baseline, 15 were assigned to the EtOH group and 13 to the control (Ctrl) group. EtOH animals were exposed to 5 cycles of 4-days of EtOH treatment followed by 10 days of recovery. Rats in both groups had structural MR imaging (MRI) scans and whole brain MR spectroscopy (MRS) at baseline, immediately following each binge period, and after each recovery period (total=11 MR scans per rat). Average blood alcohol levels (BALs) across each of the 5, 4-day binge periods were 298, 300, 301, 312, 318 mg/dL. Cerebrospinal fluid (CSF) volumes of the lateral ventricles and cisterns showed enlargement with each binge EtOH exposure but recovery with each abstinence period. Similarly, changes to MRS metabolites were transient: levels of N-acetyl aspartate (NAA) and total creatine (tCr) decreased, while those of choline-containing compounds (Cho) and glutamate/glutamine (Glx) increased with each binge EtOH exposure cycle, but also recovered during each abstinence period. The directionality of changes in response to EtOH were in expected directions based on previous, single-binge EtOH exposure experiments, but the current results do not provide support for accruing pathology with repeated binge EtOH exposure. PMID:26283309

  16. Associations between periodontitis and systemic inflammatory diseases: response to treatment.

    PubMed

    El-Shinnawi, Una; Soory, Mena

    2013-09-01

    There is a significant prevalence of subjects with periodontitis presenting with other inflammatory conditions such as coronary heart disease, insulin resistance and arthritis. This pattern of disease presentation underscores the importance of inflammatory loading from chronic diseases, in driving their pathogeneses in a multidirectional manner. Pro-inflammatory cytokines and other agents play an important role in this process; for example, a single nucleotide polymorphism of the TNF-α gene is associated with significant periodontal attachment loss in patients with coronary heart disease. Changes in gene expression associated with inflammation and lipid metabolism in response to oral infection with the periodontal pathogen Porphyromonas gingivalis (Pg) have been demonstrated in mouse models, independent of the demonstration of atherosclerotic lesions. Insulin resistance is considered to be a chronic low-grade inflammatory condition, associated with altered glucose tolerance, hypertriglyceridemia, central obesity and coronary heart disease. It is accompanied by elevated levels of IL-1, IL-6 and TNF-α also relevant to the progression of periodontitis. There is evidence that uncontrolled periodontal disease contributes to maintenance of systemic diseases, including rheumatoid arthritis (RA), with increased risk of periodontitis in subjects with RA. The periodontal pathogen Pg is significant in contributing to citrullination of proteins resulting in immune dysregulation and autoimmune responses, seen in RA. However, they are both multifactorial chronic diseases with complex etiopathogeneses that affect their presentation. Consistent but weak associations are seen for surrogate markers of periodontitis such as tooth loss, with multiple systemic conditions. Effective treatment of periodontitis would be important in reducing systemic inflammatory loading from chronic local inflammation and in achieving systemic health. Lack of a consistent cause and effect relationship

  17. Topical treatment of basal cell carcinoma with the immune response modifier imiquimod.

    PubMed

    Papakostas, Dimitrios; Stockfleth, Eggert

    2015-11-01

    Imiquimod, a TLR7 agonist, is a novel immune response modifier currently widely used in the treatment of actinic keratoses (in situ squamous cell carcinoma). Imiquimod has revolutionized the treatment of field cancerization and has been approved for the treatment of superficial basal cell carcinoma with the recommendation of a 6-week treatment strategy, offering an alternative to surgery or other destructive treatment strategies.

  18. Using pre-treatment EEG data to predict response to SSRI treatment for MDD.

    PubMed

    Khodayari-Rostamabad, Ahmad; Reilly, James P; Hasey, Gary; Debruin, Hubert; Maccrimmon, Duncan

    2010-01-01

    The problem of identifying in advance the most effective treatment agent for various psychiatric conditions remains an elusive goal. To address this challenge, we propose a machine learning (ML) methodology to predict the response to a selective serotonin reuptake inhibitor (SSRI) medication in subjects suffering from major depressive disorder (MDD), using pre-treatment electroencephalograph (EEG) measurements. The proposed feature selection technique is a modification of the method of Peng et al [10] that is based on a Kullback-Leibler (KL) distance measure. The classifier was realized as a kernelized partial least squares regression procedure, whose output is the predicted response. A low-dimensional kernelized principal component representation of the feature space was used for the purposes of visualization and clustering analysis. The overall method was evaluated using an 11-fold nested cross-validation procedure for which over 85% average prediction performance is obtained. The results indicate that ML methods hold considerable promise in predicting the efficacy of SSRI antidepressant therapy for major depression.

  19. Gender differences in multiple sclerosis epidemiology and treatment response.

    PubMed

    Magyari, Melinda

    2016-03-01

    risk neither in puberty nor in adulthood. The apparent protective effect of childbirth does not appear to reflect postnatal child exposure. The only factor that may show association with a higher MS risk in women is working in agriculture but it was based on very small numbers and cannot contribute quantitatively to the incidence of MS in women. Women are generally more prone to autoimmune diseases than men, but significant increased occurrence of some other autoimmune diseases was only found in male MS cases in the period before clinical onset. None of the investigated autoimmune diseases occurred less frequently in MS patients than in control persons. Treatment response to interferon-β, expressed in relapse rate was independently influenced by gender and the presence of NAbs, but it seems that the presence of NAbs does not affect the treatment effect differently in women and men. The results indicate that men's and women's treatment response to interferon-β is similar. Females had a higher frequency of relapses than males. Our study did not reveal only one reason for the incidence increase, but as MS is multifactorial it is presumed that the incidence increase is caused by more than one factor, because women's lifestyle has undergone tremendous changes in the last half century. Our study contributes to clarification of this issue, with the role of pregnancies on the risk of MS. It is accepted that sex hormones have a clear immunologic involvement in the female predominance in MS, but there is no knowledge yet to explain the changes over time.

  20. Autoimmune hemolytic anemia after nivolumab treatment in Hodgkin lymphoma responsive to immunosuppressive treatment. A case report.

    PubMed

    Tardy, Magalie P; Gastaud, Lauris; Boscagli, Annick; Peyrade, Frederic; Gallamini, Andrea; Thyss, Antoine

    2016-08-19

    The patients with refractory Hodgkin lymphoma have a poor prognosis. The nivolumab, an IgG4 monoclonal antibody inhibiting the program death 1 pathway has recently demonstrated its efficacy and its safety in patients with heavily pretreated refractory Hodgkin lymphoma. The side effects of this immunotherapy include autoimmune-like syndromes. A 75-year-old woman with no significant comorbidities was treated by nivolumab (3 mg/kg every 2 wk) as a third-line treatment for refractory Hodgkin lymphoma. A clinical response was observed with the first injection of nivolumab, with a reduction in superficial lymph nodes. After the second injection, the patient presented an authentic autoimmune hemolytic anemia with a profound anemia at 64 g/L and biologic characteristics of hemolysis (elevated unconjugated bilirubin, lactate dehydrogenase, and reticulocytes). The direct antiglobulin test was strongly positive for IgG antibodies, and the indirect antiglobulin test became positive with a very high level of autoantibodies. After 2 injections of nivolumab, the patient underwent a fluodeoxyglucose F 18 positron emission tomography-computed tomography, showing a partial response according to modified Cheson criteria. A treatment with prednisone (2 mg/kg), initiated after transfusion of 2 units of red blood cells, permitted the complete resolution of this autoimmune reaction after 3 months of corticotherapy. The fluodeoxyglucose F 18 positron emission tomography-computed tomography performed at the end of the corticotherapy showed a clear disease progression. Considering the very good response achieved after only 2 injections of nivolumab, the limited therapeutic resources for this old woman, and the complete resolution of the autoimmune hemolytic anemia, nivolumab was reintroduced at the same dose, with close clinical and biological monitoring. She received 6 more injections of nivolumab without recurrence of hemolysis.

  1. Children’s positive dispositional attributes, parents’ empathic responses, and children’s responses to painful pediatric oncology treatment procedures

    PubMed Central

    Harper, Felicity W. K.; Penner, Louis A.; Peterson, Amy; Albrecht, Terrance L.; Taub, Jeffrey

    2012-01-01

    Pain/distress during pediatric cancer treatments has substantial psychosocial consequences for children and families. We examined relationships between children’s positive dispositional attributes, parents’ empathic responses, and children’s pain/distress responses to treatment procedures. Participants were 41 pediatric cancer patients and parents. Several weeks before treatment, parents rated children’s resilience and positive dimensions of temperament. Parents’ pre-treatment empathic affective responses to their children were assessed. Children’s pain/distress during treatments was rated by multiple independent raters. Children’s resilience was significantly and positively associated with parents’ empathic affective responses and negatively associated with children’s pain/distress. Children’s adaptability and attention focusing also showed positive relationships (p<.10) with parents’ empathic responses. Parents’ empathic responses mediated effects of children’s resilience on children’s pain/distress. Children’s positive dispositional attributes influence their pain/distress during cancer treatments; however, these effects may be mediated by parents’ empathic responses. These relationships provide critical understanding of the influence of parent-child relationships on coping with treatment. PMID:22963185

  2. HPA axis response to psychological stress and treatment retention in residential substance abuse treatment: a prospective study.

    PubMed

    Daughters, Stacey B; Richards, Jessica M; Gorka, Stephanie M; Sinha, Rajita

    2009-12-01

    Substance abuse treatment programs are often characterized by high rates of premature treatment dropout, which increases the likelihood of relapse to drug use. Negative reinforcement models of addiction emphasize an individual's inability to tolerate stress as a key factor for understanding poor substance use treatment outcomes, and evidence indicates that dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis contributes to an individual's inability to respond adaptively to stress. The aim of the current study was to examine whether HPA axis response to stress is predictive of treatment retention among a sample of drug users in residential substance abuse treatment. Prospective study assessing treatment retention among 102 individuals enrolled in residential substance abuse treatment. Participants completed two computerized stress tasks, and HPA axis response to stress was measured via salivary cortisol at five time points from baseline (pre-stress) to 30 min post-stress exposure. The main outcome measures were treatment dropout (categorical) and total number of days in treatment (continuous). A significantly higher salivary cortisol response to stress was observed in treatment dropouts compared to treatment completers. Further, Cox proportional hazards survival analyses indicated that a higher peak cortisol response to stress was associated with a shorter number of days to treatment dropout. Results indicate that a higher salivary cortisol level in response to stress is associated with an inability to remain in substance abuse treatment. These findings are the first to document a biological marker of stress as a predictor of substance abuse treatment dropout, and support the development and implementation of treatments targeting this vulnerability.

  3. Modulation of Autophagy by Sorafenib: Effects on Treatment Response

    PubMed Central

    Prieto-Domínguez, Nestor; Ordóñez, Raquel; Fernández, Anna; García-Palomo, Andres; Muntané, Jordi; González-Gallego, Javier; Mauriz, José L.

    2016-01-01

    The multikinase inhibitor sorafenib is, at present, the only drug approved for the treatment of hepatocellular carcinoma (HCC), one of the most lethal types of cancer worldwide. However, the increase in the number of sorafenib tumor resistant cells reduces efficiency. A better knowledge of the intracellular mechanism of the drug leading to reduced cell survival could help to improve the benefits of sorafenib therapy. Autophagy is a bulk cellular degradation process activated in a broad range of stress situations, which allows cells to degrade misfolded proteins or dysfunctional organelles. This cellular route can induce survival or death, depending on cell status and media signals. Sorafenib, alone or in combination with other drugs is able to induce autophagy, but cell response to the drug depends on the complex integrative crosstalk of different intracellular signals. In cancerous cells, autophagy can be regulated by different cellular pathways (Akt-related mammalian target of rapamycin (mTOR) inhibition, 5′ AMP-activated protein kinase (AMPK) induction, dissociation of B-cell lymphoma 2 (Bcl-2) family proteins from Beclin-1), or effects of some miRNAs. Inhibition of mTOR signaling by sorafenib and diminished interaction between Beclin-1 and myeloid cell leukemia 1 (Mcl-1) have been related to induction of autophagy in HCC. Furthermore, changes in some miRNAs, such as miR-30α, are able to modulate autophagy and modify sensitivity in sorafenib-resistant cells. However, although AMPK phosphorylation by sorafenib seems to play a role in the antiproliferative action of the drug, it does not relate with modulation of autophagy. In this review, we present an updated overview of the effects of sorafenib on autophagy and its related activation pathways, analyzing in detail the involvement of autophagy on sorafenib sensitivity and resistance. PMID:27375485

  4. Initial response as a predictor of 12-week buprenorphine-naloxone treatment response in a prescription opioid-dependent population.

    PubMed

    McDermott, Katherine A; Griffin, Margaret L; Connery, Hilary S; Hilario, E Yvette; Fiellin, David A; Fitzmaurice, Garrett M; Weiss, Roger D

    2015-02-01

    Initial medication response has been shown to predict treatment outcome across a variety of substance use disorders, but no studies have examined the predictive power of initial response to buprenorphine-naloxone in the treatment of prescription opioid dependence. We therefore conducted a secondary analysis of data from the Prescription Opioid Addiction Treatment Study to determine whether initial response to buprenorphine-naloxone predicted 12-week treatment outcome in a prescription opioid-dependent population. Using data from a multisite, randomized controlled trial of buprenorphine-naloxone plus counseling for DSM-IV prescription opioid dependence (June 2006-July 2009), we conducted a secondary analysis to investigate the relationship between initial medication response and 12-week treatment outcome to establish how soon the efficacy of buprenorphine-naloxone could be predicted (N = 360). Outcomes were determined from the Substance Use Report, a self-report measure of substance use, and confirmatory urinalysis. Predictive values were calculated to determine the importance of abstinence versus use at various time points within the first month of treatment (week 1, weeks 1-2, 1-3, or 1-4) in predicting successful versus unsuccessful treatment outcome (based on abstinence or near-abstinence from opioids) in the last 4 weeks of buprenorphine-naloxone treatment (weeks 9-12). Outcome was best predicted by medication response after 2 weeks of treatment. Two weeks of initial abstinence was moderately predictive of treatment success (positive predictive value = 71%), while opioid use in both of the first 2 weeks was strongly predictive of unsuccessful treatment outcome (negative predictive value [NPV] = 84%), especially when successful outcome was defined as total abstinence from opioids in weeks 9-12 (NPV = 94%). Evaluating prescription opioid-dependent patients after 2 weeks of buprenorphine-naloxone treatment may help determine the likelihood of successful outcome at

  5. Initial response as a predictor of 12-week buprenorphine-naloxone treatment response in a prescription opioid dependent population

    PubMed Central

    McDermott, Katherine A.; Griffin, Margaret L.; Connery, Hilary S.; Hilario, E. Yvette; Fiellin, David A.; Fitzmaurice, Garrett M.; Weiss, Roger D.

    2015-01-01

    Objective Initial medication response has been shown to predict treatment outcome across a variety of substance use disorders, but no studies have examined the predictive power of initial response to buprenorphine-naloxone in the treatment of prescription opioid dependence. We therefore conducted a secondary analysis of data from the Prescription Opioid Addiction Treatment Study to determine whether initial response to buprenorphine-naloxone predicted 12-week treatment outcome in a prescription opioid-dependent population. Method Using data from a multi-site, randomized controlled trial of buprenorphine-naloxone plus counseling for DSM-IV prescription opioid dependence (June 2006–July 2009), we conducted a secondary analysis to investigate the relationship between initial medication response and 12-week treatment outcome to establish how soon the efficacy of buprenorphine-naloxone could be predicted. Outcomes were determined from the Substance Use Report, a self-report measure of substance use, and confirmatory urinalysis. Predictive values were calculated to determine the importance of abstinence vs. use at various time points within the first month of treatment (week 1, weeks 1–2, 1–3, or 1–4) in predicting successful vs. unsuccessful treatment outcome (based on abstinence or near-abstinence from opioids) in the last 4 weeks of buprenorphine-naloxone treatment (weeks 9–12). Results Outcome was best predicted by medication response after two weeks of treatment. Two weeks of initial abstinence was moderately predictive of treatment success (positive predictive value = 71%), while opioid use in both of the first two weeks was strongly predictive of unsuccessful treatment outcome (negative predictive value (NPV) = 84%), especially when successful outcome was defined as total abstinence from opioids in weeks 9–12 (NPV = 94%). Conclusion Evaluating prescription opioid-dependent patients after two weeks of buprenorphine-naloxone treatment may help determine

  6. INTENSIVE RESIDENTIAL TREATMENT FOR SEVERE OBSESSIVE-COMPULSIVE DISORDER: CHARACTERIZING TREATMENT COURSE AND PREDICTORS OF RESPONSE

    PubMed Central

    Brennan, Brian P.; Lee, Catherine; Elias, Jason A.; Crosby, Jesse M.; Mathes, Brittany M.; Andre, Marie-Christine; Gironda, Christina M.; Pope, Harrison G.; Jenike, Michael A.; Fitzmaurice, Garrett M.; Hudson, James I.

    2014-01-01

    Background Intensive residential treatment (IRT) is effective for severe, treatment-resistant obsessive-compulsive disorder (OCD). We sought to characterize predictors and course of response to IRT. Methods Admission, monthly, and discharge data were collected on individuals receiving IRT. We examined the association between baseline characteristics and percent change in OCD symptoms as measured by the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) using linear regression. We compared baseline characteristics of IRT responders (≥35% reduction in Y-BOCS) versus non-responders, and of patients who did versus those who did not achieve wellness (Y-BOCS ≤12) using non-parametric tests. To examine the course of OCD severity over time, we used linear mixed-effects models with randomly varying intercepts and slopes. Results We evaluated 281 individuals admitted to an IRT program. Greater baseline Y-BOCS scores were associated with a significantly greater percent reduction in Y-BOCS scores (β = −1.49 ([95% confidence interval: −2.06 to −0.93]; P<.001). IRT responders showed significantly greater baseline Y-BOCS scores than non-responders (mean (SD) 28 (5.2) vs. 25.6 (5.8); P=.003) and lower past-year alcohol use scores than non-responders (1.4 (1.9) vs. 2.1 (2.2); P=.01). Participants who achieved wellness displayed lower hoarding factor scores than those who did not (5 (4.6) vs. 9.53 (6.3); P=.03). OCD symptoms declined rapidly over the first month but more slowly over the remaining two months. Conclusions Higher baseline OCD severity, lower past-year alcohol use, and fewer hoarding symptoms predicted better response to IRT. IRT yielded an initial rapid reduction in OCD symptoms, followed by a slower decline after the first month. PMID:24909787

  7. Treatment-Resistant Schizophrenia: Treatment Response and Resistance in Psychosis (TRRIP) Working Group Consensus Guidelines on Diagnosis and Terminology.

    PubMed

    Howes, Oliver D; McCutcheon, Rob; Agid, Ofer; de Bartolomeis, Andrea; van Beveren, Nico J M; Birnbaum, Michael L; Bloomfield, Michael A P; Bressan, Rodrigo A; Buchanan, Robert W; Carpenter, William T; Castle, David J; Citrome, Leslie; Daskalakis, Zafiris J; Davidson, Michael; Drake, Richard J; Dursun, Serdar; Ebdrup, Bjørn H; Elkis, Helio; Falkai, Peter; Fleischacker, W Wolfgang; Gadelha, Ary; Gaughran, Fiona; Glenthøj, Birte Y; Graff-Guerrero, Ariel; Hallak, Jaime E C; Honer, William G; Kennedy, James; Kinon, Bruce J; Lawrie, Stephen M; Lee, Jimmy; Leweke, F Markus; MacCabe, James H; McNabb, Carolyn B; Meltzer, Herbert; Möller, Hans-Jürgen; Nakajima, Shinchiro; Pantelis, Christos; Reis Marques, Tiago; Remington, Gary; Rossell, Susan L; Russell, Bruce R; Siu, Cynthia O; Suzuki, Takefumi; Sommer, Iris E; Taylor, David; Thomas, Neil; Üçok, Alp; Umbricht, Daniel; Walters, James T R; Kane, John; Correll, Christoph U

    2017-03-01

    Research and clinical translation in schizophrenia is limited by inconsistent definitions of treatment resistance and response. To address this issue, the authors evaluated current approaches and then developed consensus criteria and guidelines. A systematic review of randomized antipsychotic clinical trials in treatment-resistant schizophrenia was performed, and definitions of treatment resistance were extracted. Subsequently, consensus operationalized criteria were developed through 1) a multiphase, mixed methods approach, 2) identification of key criteria via an online survey, and 3) meetings to achieve consensus. Of 2,808 studies identified, 42 met inclusion criteria. Of these, 21 studies (50%) did not provide operationalized criteria. In the remaining studies, criteria varied considerably, particularly regarding symptom severity, prior treatment duration, and antipsychotic dosage thresholds; only two studies (5%) utilized the same criteria. The consensus group identified minimum and optimal criteria, employing the following principles: 1) current symptoms of a minimum duration and severity determined by a standardized rating scale; 2) moderate or worse functional impairment; 3) prior treatment consisting of at least two different antipsychotic trials, each for a minimum duration and dosage; 4) systematic monitoring of adherence and meeting of minimum adherence criteria; 5) ideally at least one prospective treatment trial; and 6) criteria that clearly separate responsive from treatment-resistant patients. There is considerable variation in current approaches to defining treatment resistance in schizophrenia. The authors present consensus guidelines that operationalize criteria for determining and reporting treatment resistance, adequate treatment, and treatment response, providing a benchmark for research and clinical translation.

  8. Six-Month Response to Delamanid Treatment in MDR TB Patients.

    PubMed

    Hewison, Cathy; Ferlazzo, Gabriella; Avaliani, Zaza; Hayrapetyan, Armen; Jonckheere, Sylvie; Khaidarkhanova, Zarema; Mohr, Erika; Sinha, Animesh; Skrahina, Alena; Vambe, Debrah; Vasilyeva, Irina; Lachenal, Nathalie; Varaine, Francis

    2017-10-01

    Delamanid, recently available for the treatment of multidrug-resistant tuberculosis (MDR TB), has had limited use outside clinical trials. We present the early treatment results for 53 patients from 7 countries who received a delamanid-containing treatment for MDR TB. Results show good tolerability and treatment response at 6 months.

  9. Bryoid layer response to soil disturbance by fuel reduction treatments in a dry conifer forest

    Treesearch

    Amanda Hardman; Bruce McCune

    2010-01-01

    We investigated the response of the bryoid layer, bryophyte and lichen communities on the soil surface three years after fuel reduction treatment (logging and burning) in the central Blue Mountains of eastern Oregon. Both treatment and control areas had been decimated by spruce budworm and drought before the fuel reduction treatments. Treatments reduced overstory and...

  10. Income received during treatment does not affect response to contingency management treatments in cocaine-dependent outpatients

    PubMed Central

    Andrade, Leonardo F.; Petry, Nancy M.

    2013-01-01

    Background Prior studies find no effect of baseline income on response to contingency management (CM) interventions. However, income among substance disordered patients is variable, particularly at treatment entry. This study investigated the impact of during-treatment income, a more proximal estimate of economic resources at the time that CM is in effect, on response to standard treatment or the standard treatment plus CM. Method These secondary analyses included 418 cocaine dependent participants initiating community intensive outpatient treatment. We examined whether differences were present in pretreatment and during-treatment overall income, as well as specific income sources. We then conducted a series of regression models to investigate the impact of during-treatment income on treatment outcome. Results Participants’ during-treatment income was significantly lower compared to pretreatment income, and this difference was largely attributable to decreases in earned income, illegal income, and support from friends and family. Neither the main effect of income, nor the interaction of income and treatment condition, was significantly associated with treatment outcome. CM, however, was a significant predictor of improved treatment outcome relative to standard treatment. Income sources and some demographic characteristics were also significant predictors of outcomes; public assistance income was associated with improved outcomes and illegal income was associated with poorer outcomes. Conclusions These results suggest that substance abusers benefit from CM regardless of their income level, and these data add to the growing literature supporting the generalizability of CM across a variety of patient characteristics. PMID:23631869

  11. Critical incidents and judicial response during medium security treatment.

    PubMed

    Jeandarme, Inge; Wittouck, Ciska; Vander Laenen, Freya; Pouls, Claudia; Heimans, Henri; Oei, T I; Bogaerts, Stefan

    This study examined inpatient incidents in three Flemish forensic medium security units and analyzed the subsequent judicial reactions to these incidents. During medium security treatment, incidents were reported for more than half of the participants. The most frequently registered incidents were non-violent in nature, such as absconding and treatment non-compliance. The base rate for physically violent incidents was low. Although crime-related incidents during medium security treatment were rarely prosecuted and adjudicated, the base rate of revocation - and hence drop-out from treatment - as a result of these incidents was high.

  12. Using host response modifiers in the treatment of periodontal disease.

    PubMed

    Novak, M John; Donley, Timothy G

    2002-01-01

    Periodontal disease is the result of a complex interaction between microbial plaque, the host's inflammatory response to the plaque, and host modifying factors (e.g., smoking, diabetes, genetics) that may have an impact on the disease process. It is known that plaque initiates periodontal disease but that the host response is responsible for the destruction of periodontal tissues. This article describes why host response modifiers may be used to help control inflammation and tissue destruction as part of the initial phase of periodontal therapy in selected patient groups.

  13. Transcriptional profiling of apple fruits in response to heat treatment: involvement of a defense response during P. expansum infection

    USDA-ARS?s Scientific Manuscript database

    Heat treatment of harvested fruit has been demonstrated to be an effective and safe approach for managing postharvest decay. In the present study, the effect of a hot water treatment (HT) (45 degrees C for 10 minutes) on the response of apple to blue mold infection was investigated. HT was applied...

  14. Heterogeneity Moderates Treatment Response among Patients with Binge Eating Disorder

    ERIC Educational Resources Information Center

    Sysko, Robyn; Hildebrandt, Tom; Wilson, G. Terence; Wilfley, Denise E.; Agras, W. Stewart

    2010-01-01

    Objective: The purpose of the study was to explore heterogeneity and differential treatment outcome among a sample of patients with binge eating disorder (BED). Method: A latent class analysis was conducted with 205 treatment-seeking, overweight or obese individuals with BED randomized to interpersonal psychotherapy (IPT), behavioral weight loss…

  15. Heterogeneity Moderates Treatment Response among Patients with Binge Eating Disorder

    ERIC Educational Resources Information Center

    Sysko, Robyn; Hildebrandt, Tom; Wilson, G. Terence; Wilfley, Denise E.; Agras, W. Stewart

    2010-01-01

    Objective: The purpose of the study was to explore heterogeneity and differential treatment outcome among a sample of patients with binge eating disorder (BED). Method: A latent class analysis was conducted with 205 treatment-seeking, overweight or obese individuals with BED randomized to interpersonal psychotherapy (IPT), behavioral weight loss…

  16. Three cases of paraphilias responsive to fluoxetine treatment.

    PubMed

    Perilstein, R D; Lipper, S; Friedman, L J

    1991-04-01

    Three cases are presented in which fluoxetine was employed in the apparently successful treatment of paraphilia, a disorder which has been difficult to treat pharmacologically. Therapeutic benefit may have been related to the efficacy of fluoxetine in the treatment of obsessive compulsive disorders or to direct effects on sexual activity, or both.

  17. Effectiveness of Antidepressants and Predictors of Treatment Response for Depressed HIV Patients in Uganda

    PubMed Central

    Ngo, Victoria K.; Wagner, Glenn J.; Nakasujja, Noeline; Dickens, Akena; Aunon, Frances; Musisi, Seggane

    2015-01-01

    Antidepressant medication is well-established for the treatment of depression, but little is known about its effectiveness for HIV populations in sub-Saharan Africa. This study examined the effectiveness of antidepressant treatment and predictors of treatment response among depressed HIV patients in Uganda. Data was obtained from two open label trials in which 184 HIV patients were diagnosed with depression and started on antidepressants. Data at treatment baseline and month 6 were compared to assess treatment response, and baseline predictors of response were assessed. 154 completed Month 6, of whom 122 (79%) had responded to treatment and were no longer depressed (Patient Health Questionnaire-9 score < 5). Bivariate analysis found that education, CD4 count, general health functioning, physical health, pain, quality of life, and social support variables were associated with antidepressant treatment response; however, only secondary education and social support independently predicted treatment response in logistic multiple regression analysis. Baseline depression severity was not associated with treatment response. In conclusion, antidepressants are effective in treating both moderate and more severe depression among persons living with HIV in Uganda, and education [O.R. (95% C.I.) = 4.33 (1.33 – 14.11)] and social support [O.R. (95% C.I.) = 1.54 (1.03 – 2.30)] were most predictive of treatment response. PMID:25525053

  18. Impact of Physical and Sexual Abuse on Treatment Response in the Treatment of Resistant Depression in Adolescent Study (TORDIA)

    ERIC Educational Resources Information Center

    Shamseddeen, Wael; Asarnow, Joan Rosenbaum; Clarke, Gregory; Vitiello, Benedetto; Wagner, Karen Dineen; Birmaher, Boris; Keller, Martin B.; Emslie, Graham; Iyengar, Satish; Ryan, Neal D.; McCracken, James T.; Porta, Giovanna; Mayes, Taryn; Brent, David A.

    2011-01-01

    Objective: We previously reported that a history of abuse was associated with a poorer response to combination treatment in the Treatment of Resistant Depression in Adolescents study (TORDIA). We now report on the nature and correlates of abuse that might explain these findings. Method: Youth who did not benefit from an adequate selective…

  19. Treatment-Resistant Depressed Youth Show a Higher Response Rate If Treatment Ends during Summer School Break

    ERIC Educational Resources Information Center

    Shamseddeen, Wael; Clarke, Gregory; Wagner, Karen Dineen; Ryan, Neal D.; Birmaher, Boris; Emslie, Graham; Asarnow, Joan Rosenbaum; Porta, Giovanna; Mayes, Taryn; Keller, Martin B.; Brent, David A.

    2011-01-01

    Objective: There is little work on the effect of school on response to treatment of depression, with available research suggesting that children and adolescents with school difficulties are less likely to respond to fluoxetine compared with those with no school difficulties. Method: Depressed adolescents in the Treatment of Resistant Depression in…

  20. Impact of Physical and Sexual Abuse on Treatment Response in the Treatment of Resistant Depression in Adolescent Study (TORDIA)

    ERIC Educational Resources Information Center

    Shamseddeen, Wael; Asarnow, Joan Rosenbaum; Clarke, Gregory; Vitiello, Benedetto; Wagner, Karen Dineen; Birmaher, Boris; Keller, Martin B.; Emslie, Graham; Iyengar, Satish; Ryan, Neal D.; McCracken, James T.; Porta, Giovanna; Mayes, Taryn; Brent, David A.

    2011-01-01

    Objective: We previously reported that a history of abuse was associated with a poorer response to combination treatment in the Treatment of Resistant Depression in Adolescents study (TORDIA). We now report on the nature and correlates of abuse that might explain these findings. Method: Youth who did not benefit from an adequate selective…

  1. Treatment-Resistant Depressed Youth Show a Higher Response Rate If Treatment Ends during Summer School Break

    ERIC Educational Resources Information Center

    Shamseddeen, Wael; Clarke, Gregory; Wagner, Karen Dineen; Ryan, Neal D.; Birmaher, Boris; Emslie, Graham; Asarnow, Joan Rosenbaum; Porta, Giovanna; Mayes, Taryn; Keller, Martin B.; Brent, David A.

    2011-01-01

    Objective: There is little work on the effect of school on response to treatment of depression, with available research suggesting that children and adolescents with school difficulties are less likely to respond to fluoxetine compared with those with no school difficulties. Method: Depressed adolescents in the Treatment of Resistant Depression in…

  2. Hypnotic responsivity and the treatment of flying phobia.

    PubMed

    Spiegel, David; Maruffi, Brian; Frischholz, Edward J; Spiegel, Herbert

    2015-01-01

    Systematic follow-up data are reported for 178 consecutive flying phobia patients treated with a single 45-minute session involving hypnosis and a problem restructuring strategy. One hundred fifty-eight (89%) of the patients completed follow-up questionnaires between six months and ten and one half years after treatment. Results showed that hypnotizable patients were over two and one half times more likely to report some positive treatment impact than those who were found to be nonhypnotizable on the Hypnotic Induction Profile. In addition, the patients' previous experiences with psychotherapy were found to be significantly associated with treatment outcome. The clinical implications of these findings are discussed.

  3. Rapid Response Predicts Treatment Outcomes in Binge Eating Disorder: Implications for Stepped Care

    ERIC Educational Resources Information Center

    Masheb, Robin M.; Grilo, Carlos M.

    2007-01-01

    The authors examined rapid response in 75 overweight patients with binge eating disorder (BED) who participated in a randomized clinical trial of guided self-help treatments (cognitive-behavioral therapy [CBTgsh] and behavioral weight loss [BWLgsh]). Rapid response, defined as a 65% or greater reduction in binge eating by the 4th treatment week,…

  4. Neural Mechanisms of Improvements in Social Motivation after Pivotal Response Treatment: Two Case Studies

    ERIC Educational Resources Information Center

    Voos, Avery C.; Pelphrey, Kevin A.; Tirrell, Jonathan; Bolling, Danielle Z.; Vander Wyk, Brent; Kaiser, Martha D.; McPartland, James C.; Volkmar, Fred R.; Ventola, Pamela

    2013-01-01

    Pivotal response treatment (PRT) is an empirically validated behavioral treatment that has widespread positive effects on communication, behavior, and social skills in young children with autism spectrum disorder (ASD). For the first time, functional magnetic resonance imaging was used to identify the neural correlates of successful response to…

  5. Neural Mechanisms of Improvements in Social Motivation after Pivotal Response Treatment: Two Case Studies

    ERIC Educational Resources Information Center

    Voos, Avery C.; Pelphrey, Kevin A.; Tirrell, Jonathan; Bolling, Danielle Z.; Vander Wyk, Brent; Kaiser, Martha D.; McPartland, James C.; Volkmar, Fred R.; Ventola, Pamela

    2013-01-01

    Pivotal response treatment (PRT) is an empirically validated behavioral treatment that has widespread positive effects on communication, behavior, and social skills in young children with autism spectrum disorder (ASD). For the first time, functional magnetic resonance imaging was used to identify the neural correlates of successful response to…

  6. Rapid Response Predicts Treatment Outcomes in Binge Eating Disorder: Implications for Stepped Care

    ERIC Educational Resources Information Center

    Masheb, Robin M.; Grilo, Carlos M.

    2007-01-01

    The authors examined rapid response in 75 overweight patients with binge eating disorder (BED) who participated in a randomized clinical trial of guided self-help treatments (cognitive-behavioral therapy [CBTgsh] and behavioral weight loss [BWLgsh]). Rapid response, defined as a 65% or greater reduction in binge eating by the 4th treatment week,…

  7. An Evaluation of Response Cost in the Treatment of Inappropriate Vocalizations Maintained by Automatic Reinforcement

    ERIC Educational Resources Information Center

    Falcomata, Terry S.; Roane, Henry S.; Hovanetz, Alyson N.; Kettering, Tracy L.; Keeney, Kris M.

    2004-01-01

    In the current study, we examined the utility of a procedure consisting of noncontingent reinforcement with and without response cost in the treatment of inappropriate vocalizations maintained by automatic reinforcement. Results are discussed in terms of examining the variables that contribute to the effectiveness of response cost as treatment for…

  8. An evaluation of response cost in the treatment of inappropriate vocalizations maintained by automatic reinforcement.

    PubMed

    Falcomata, Terry S; Roane, Henry S; Hovanetz, Alyson N; Kettering, Tracy L; Keeney, Kris M

    2004-01-01

    In the current study, we examined the utility of a procedure consisting of noncontingent reinforcement with and without response cost in the treatment of inappropriate vocalizations maintained by automatic reinforcement. Results are discussed in terms of examining the variables that contribute to the effectiveness of response cost as treatment for problem behavior maintained by automatic reinforcement.

  9. Inflammatory response in heroin addicts undergoing methadone maintenance treatment.

    PubMed

    Chan, Yuan-Yu; Yang, Szu-Nian; Lin, Jyh-Chyang; Chang, Junn-Liang; Lin, Jaung-Geng; Lo, Wan-Yu

    2015-03-30

    Opioid addiction influences many physiological functions including reactions of the immune system. The objective of this study was to investigate the immune system function in heroin addicted patients undergoing methadone maintenance treatment (MMT) compared to healthy controls. We tested the cytokine production of IL-1β, IL-6, IL-8, IL-10 and tumor necrosis factor (TNF)-α from a group of heroin addicts (n=34) and healthy controls (n=20). The results show that production of IL-1β, IL-6 and IL-8 was significantly higher in the group of methadone-maintained patients than in the healthy control group. Plasma TNF-α and IL-6 levels were significantly correlated with the dairy methadone dosage administered, and the IL-1β level was significantly correlated with the duration of methadone maintenance treatment. These findings suggest that methadone maintenance treatment influences the immune system functions of opioid-dependent patients and may also induce long-term systemic inflammation.

  10. Adolescent Eating Disorders: Treatment and Response in a Naturalistic Study

    PubMed Central

    Thompson-Brenner, Heather; Boisseau, Christina L.; Satir, Dana A.

    2014-01-01

    This naturalistic study investigated the treatment and outcome of adolescents with eating disorders (EDs) in the community. Clinicians from a practice-research network provided data on ED symptoms, global functioning, comorbidity, treatment, and outcome for 120 adolescents with EDs. ED “not otherwise specified” was the most common ED diagnosed. After an average of 8 months of treatment, about one third of patients had recovered, with patients with anorexia nervosa showing the most improvement. Clinicians utilized a range of psychotherapy interventions and two thirds of the patients had received adjunct psychoactive medication. Although CBT showed the strongest association with outcome in a subsample characterized by poor relational/personality functioning, dynamic therapy was associated with better global outcome in the overall sample. PMID:19938166

  11. Behavioral activation: a strategy to enhance treatment response.

    PubMed

    Sudak, Donna M; Majeed, Muhammad H; Youngman, Branden

    2014-07-01

    Behavioral activation is an empirically validated treatment for depression pioneered in 1973 by Ferster, based on B.F. Skinner's behavioral principles. After publication of Beck's work on cognitive therapy, the boundaries of behavioral and cognitive therapies were blurred and the two now overlap substantially. Behavioral activation is also used as a stand-alone treatment and can also be effective in conjunction with antidepressant medication. Case conceptualization in behavioral activation entails an assessment of the behaviors that the patient has stopped that produce pleasure or are of importance, as well as behaviors essential to self-care. Activity monitoring, which provides treatment targets and leads to the case conceptualization in behavioral activation, consists of using charts, forms, or other prompts to track the relationship between activities and other variables (e.g., mood, enjoyment). That technique is also used to target rumination, procrastination, and avoidance and may also be helpful for patients with psychosis.

  12. Adolescent eating disorders: treatment and response in a naturalistic study.

    PubMed

    Thompson-Brenner, Heather; Boisseau, Christina L; Satir, Dana A

    2010-03-01

    This naturalistic study investigated the treatment and outcome of adolescents with eating disorders (EDs) in the community. Clinicians from a practice-research network provided data on ED symptoms, global functioning, comorbidity, treatment, and outcome for 120 adolescents with EDs. ED "not otherwise specified" was the most common ED diagnosed. After an average of 8 months of treatment, about one third of patients had recovered, with patients with anorexia nervosa showing the most improvement. Clinicians utilized a range of psychotherapy interventions and two thirds of the patients had received adjunct psychoactive medication. Although CBT showed the strongest association with outcome in a subsample characterized by poor relational/personality functioning, dynamic therapy was associated with better global outcome in the overall sample. Copyright 2009 Wiley Periodicals, Inc.

  13. Genetic factors affecting patient responses to pancreatic cancer treatment

    PubMed Central

    Fotopoulos, George; Syrigos, Konstantinos; Saif, Muhammad Wasif

    2016-01-01

    Cancer of the exocrine pancreas is a malignancy with a high lethal rate. Surgical resection is the only possible curative mode of treatment. Metastatic pancreatic cancer is incurable with modest results from the current treatment options. New genomic information could prove treatment efficacy. An independent review of PubMed and ScienceDirect databases was performed up to March 2016, using combinations of terms such pancreatic exocrine cancer, chemotherapy, genomic profile, pancreatic cancer pharmacogenomics, genomics, molecular pancreatic pathogenesis, and targeted therapy. Recent genetic studies have identified new markers and therapeutic targets. Our current knowledge of pancreatic cancer genetics must be further advanced to elucidate the molecular basis and pathogenesis of the disease, improve the accuracy of diagnosis, and guide tailor-made therapies. PMID:27708512

  14. Current Approaches, Challenges and Future Directions for Monitoring Treatment Response in Prostate Cancer

    PubMed Central

    Wallace, T.J.; Torre, T.; Grob, M.; Yu, J.; Avital, I.; Brücher, BLDM; Stojadinovic, A.; Man, Y.G.

    2014-01-01

    Prostate cancer is the most commonly diagnosed non-cutaneous neoplasm in men in the United States and the second leading cause of cancer mortality. One in 7 men will be diagnosed with prostate cancer during their lifetime. As a result, monitoring treatment response is of vital importance. The cornerstone of current approaches in monitoring treatment response remains the prostate-specific antigen (PSA). However, with the limitations of PSA come challenges in our ability to monitor treatment success. Defining PSA response is different depending on the individual treatment rendered potentially making it difficult for those not trained in urologic oncology to understand. Furthermore, standard treatment response criteria do not apply to prostate cancer further complicating the issue of treatment response. Historically, prostate cancer has been difficult to image and no single modality has been consistently relied upon to measure treatment response. However, with newer imaging modalities and advances in our understanding and utilization of specific biomarkers, the future for monitoring treatment response in prostate cancer looks bright. PMID:24396494

  15. Pivotal Response Treatment Parent Training for Autism: Findings from a 3-Month Follow-Up Evaluation

    ERIC Educational Resources Information Center

    Gengoux, Grace W.; Berquist, Kari L.; Salzman, Emma; Schapp, Salena; Phillips, Jennifer M.; Frazier, Thomas W.; Minjarez, Mendy B.; Hardan, Antonio Y.

    2015-01-01

    This study's objective was to assess maintenance of treatment effects 3 months after completion of a 12-week Pivotal Response Treatment (PRT) parent education group. Families who completed the active treatment (N = 23) were followed for an additional 12 weeks to measure changes in language and cognitive skills. Results indicated a significant…

  16. Brief Parent Training in Pivotal Response Treatment for Preschoolers with Autism

    ERIC Educational Resources Information Center

    Coolican, Jamesie; Smith, Isabel M.; Bryson, Susan E.

    2010-01-01

    Background: Evidence of improved outcomes with early behavioural intervention has placed the early treatment of autism as a health priority. However, long waiting lists for treatment often preclude timely access, raising the question of whether parents could be trained in the interim. Parent training in pivotal response treatment (PRT) has been…

  17. Loblolly pine growth response to mid-rotational treatments in an Eastern Texas plantation

    Treesearch

    Mohammad M. Bataineh; Amanda L. Bataineh; Brian P. Oswald; Kenneth W. Farrish; Hans M. Williams

    2006-01-01

    The effects of mid-rotational treatments (herbicide, prescribed burn, combination of herbicide and burn, and fertilization) on growth of loblolly pine were evaluated. Five replicates were established in a split-plot experimental design with fertilizer treatments as the whole-plot factor and competition control treatments as the sub-plot factor. Growth response was...

  18. Pivotal Response Treatment Parent Training for Autism: Findings from a 3-Month Follow-Up Evaluation

    ERIC Educational Resources Information Center

    Gengoux, Grace W.; Berquist, Kari L.; Salzman, Emma; Schapp, Salena; Phillips, Jennifer M.; Frazier, Thomas W.; Minjarez, Mendy B.; Hardan, Antonio Y.

    2015-01-01

    This study's objective was to assess maintenance of treatment effects 3 months after completion of a 12-week Pivotal Response Treatment (PRT) parent education group. Families who completed the active treatment (N = 23) were followed for an additional 12 weeks to measure changes in language and cognitive skills. Results indicated a significant…

  19. Life Stress and Treatment Course of Recurrent Depression: 1. Response during Index Episode.

    ERIC Educational Resources Information Center

    Monroe, Scott M.; And Others

    1992-01-01

    Conducted prospective study of 91 individuals treated for recurrent depression. Specific forms of stress occurring before treatment entry or during first 6 weeks of treatment predicted poor clinical response both after 16 weeks and after more extended intervention period. Severe stress occurring early in treatment predicted loner time to attain…

  20. Understory response to fuel reduction treatments in the Blue Mountains of northeastern Oregon.

    Treesearch

    Kerry L. Metlen; Carl E. Fiedler; Andrew. Youngblood

    2004-01-01

    Understory response to fuel reduction treatments was evaluated in fire-adapted ponderosa pine-Douglas-fir forests in northeastern Oregon. Treatments included: no management (control), prescribed fall burning (burn), low thinning (thin), and low thinning followed by prescribed fall burning (thin/burn), replicated four times in a completely randomized design. Treatment...

  1. Loss of Response to Melatonin Treatment Is Associated with Slow Melatonin Metabolism

    ERIC Educational Resources Information Center

    Braam, W.; van Geijlswijk, I.; Keijzer, Henry; Smits, Marcel G.; Didden, Robert; Curfs, Leopold M. G.

    2010-01-01

    Background: In some of our patients with intellectual disability (ID) and sleep problems, the initial good response to melatonin disappeared within a few weeks after starting treatment, while the good response returned only after considerable dose reduction. The cause for this loss of response to melatonin is yet unknown. We hypothesise that this…

  2. Loss of Response to Melatonin Treatment Is Associated with Slow Melatonin Metabolism

    ERIC Educational Resources Information Center

    Braam, W.; van Geijlswijk, I.; Keijzer, Henry; Smits, Marcel G.; Didden, Robert; Curfs, Leopold M. G.

    2010-01-01

    Background: In some of our patients with intellectual disability (ID) and sleep problems, the initial good response to melatonin disappeared within a few weeks after starting treatment, while the good response returned only after considerable dose reduction. The cause for this loss of response to melatonin is yet unknown. We hypothesise that this…

  3. Perceptions of the Causes of Obesity and Responsiveness to Treatment.

    ERIC Educational Resources Information Center

    Hartigan, Kevin J.; And Others

    1982-01-01

    Examined whether obese subjects' causal attributions of their weight problems to ability, effort, task difficulty, and luck affect how much weight they lose as a function of treatment. Results indicated the most powerful predictor of positive weight status was subjects' perception that they had the ability to lose weight. (Author)

  4. Response to acupuncture treatment in horses with chronic laminitis.

    PubMed

    Faramarzi, Babak; Lee, Dongbin; May, Kevin; Dong, Fanglong

    2017-08-01

    There is a need for evidence-based scientific research to address the question of the effectiveness of acupuncture in improving clinical signs of laminitis in horses. The objective of this study was to compare lameness levels before and after 2 acupuncture treatments in horses with chronic laminitis. Twelve adult horses with chronic laminitis received 2 acupuncture treatments 1 week apart. The points were treated using dry needling, hemo-acupuncture, and aqua-acupuncture. Lameness level was objectively evaluated using an inertial sensor-based lameness evaluation system (Lameness Locator), as well as routine examinations following American Association of Equine Practitioners scoring before the first and 1 week after the second acupuncture treatment. Data were analyzed using Wilcoxon signed-rank test and P-values < 0.05 were considered statistically significant. Both the Lameness Locator (P = 0.0269) and routine lameness examination (P = 0.0039) showed a significant reduction in lameness severity. Our results support using acupuncture, along with other treatment options, in treating chronic equine laminitis.

  5. Neurobiology of Sleep and Sleep Treatment Response in PTSD

    DTIC Science & Technology

    2009-10-01

    nightmares, dreaming and REM sleep may provide a unique psychophvsiological milieu dur- lllg which traumatic memories can he reexperienced in the absence of...physioiogiccli arousal. This process could f,lCilitate the attenuation of emotional and physio- logical responses associated with these memories ...subserving emotional processing and integration of trauma- related memories . Specifically, it is suggested that REM sleep provides a unique

  6. Association between gene variants and response to buprenorphine maintenance treatment.

    PubMed

    Gerra, Gilberto; Somaini, Lorenzo; Leonardi, Claudio; Cortese, Elena; Maremmani, Icro; Manfredini, Matteo; Donnini, Claudia

    2014-01-30

    A variety of studies were addressed to differentiate responders and non-responders to substitution treatment among heroin dependent patients, without conclusive findings. In particular, preliminary pharmacogenetic findings have been reported to predict treatment effectiveness in mental health and substance use disorders. Aim of the present study was to investigate the possible association of buprenorphine (BUP) treatment outcome with gene variants that may affect kappa-opioid receptors and dopamine system function. One hundred and seven heroin addicts (West European, Caucasians) who underwent buprenorphine maintenance treatment were genotyped and classified into two groups (A and B) on the basis of treatment outcome. Non-responders to buprenorphine (group B) have been identified taking into account early drop out, continuous use of heroin, severe behavioral or psychiatric problems, misbehavior and diversion during the 6 months treatment period. No difference was evidenced between responders and non-responders to BUP in the frequency of kappa opioid receptor (OPRK1) 36G>T SNP. The frequency of dopamine transporter (DAT) gene polymorphism (SLC6A3/DAT1), allele 10, was evidently much higher in "non-responder" than in "responder" individuals (64.9% vs. 55.93%) whereas the frequency of the category of other alleles (6, 7 and 11) was higher in responder than in non-responder individuals (11.02% vs. 2.13% respectively). On one hand, the hypothesis that possible gene-related changes in kappa-opioid receptor could consistently affect buprenorphine pharmacological action and clinical effectiveness was not confirmed in our study, at least in relation to the single nucleotide polymorphism 36G>T. On the other hand, the possibility that gene-related dopamine changes could have reduced BUP effectiveness and impaired maintenance treatment outcome was cautiously supported by our findings. DAT1 gene variants such as allele 10, previously reported in association with personality and

  7. Determinants of Pain Treatment Response and Non-Response: Identification of TMD Patient Subgroups

    PubMed Central

    Litt, Mark D.; Porto, Felipe B.

    2013-01-01

    The purpose of the present study was to determine if we could identify a specific subtype of temporomandibular disorder (TMD) pain patients that does not respond to treatment. Patients were 101 men and women with chronic TMD pain recruited from the community and randomly assigned to one of two treatment conditions: a standard conservative care (STD) condition or a standard care plus cognitive-behavioral treatment condition (STD+CBT) in which patients received all elements of STD, but also received cognitive-behavioral coping skills training. Growth mixture modeling, incorporating a series of treatment-related predictors, was used to distinguish several distinct classes of responders or non-responders to treatment based on reported pain over a one-year follow-up period. Results indicated that treatment non-responders accounted for 16% of the sample, and did not differ from treatment responders on demographics or temporomandibular joint pathology, but that they reported more psychiatric symptoms, poorer coping, and higher levels of catastrophizing. Treatment-related predictors of membership in treatment responder groups versus the non-responder group included the addition of CBT to standard treatment, treatment attendance, and decreasing catastrophization. It was concluded that CBT may be made more efficacious for TMD patients by placing further emphasis on decreasing catastrophization and on individualizing care. PMID:24094979

  8. Neural Reactivity to Angry Faces Predicts Treatment Response in Pediatric Anxiety.

    PubMed

    Bunford, Nora; Kujawa, Autumn; Fitzgerald, Kate D; Swain, James E; Hanna, Gregory L; Koschmann, Elizabeth; Simpson, David; Connolly, Sucheta; Monk, Christopher S; Phan, K Luan

    2017-02-01

    Although cognitive-behavioral psychotherapy (CBT) and pharmacotherapy are evidence-based treatments for pediatric anxiety, many youth with anxiety disorders fail to respond to these treatments. Given limitations of clinical measures in predicting treatment response, identifying neural predictors is timely. In this study, 35 anxious youth (ages 7-19 years) completed an emotional face-matching task during which the late positive potential (LPP), an event-related potential (ERP) component that indexes sustained attention towards emotional stimuli, was measured. Following the ERP measurement, youth received CBT or selective serotonin reuptake inhibitor (SSRI) treatment, and the LPP was examined as a predictor of treatment response. Findings indicated that, accounting for pre-treatment anxiety severity, neural reactivity to emotional faces predicted anxiety severity post- CBT and SSRI treatment such that enhanced electrocortical response to angry faces was associated with better treatment response. An enhanced LPP to angry faces may predict treatment response insofar as it may reflect greater emotion dysregulation or less avoidance and/or enhanced engagement with environmental stimuli in general, including with treatment.

  9. Treatment Response to an Intensive Summer Treatment Program for Adolescents with ADHD

    ERIC Educational Resources Information Center

    Sibley, Margaret H.; Smith, Bradley H.; Evans, Steven W.; Pelham, William E.; Gnagy, Elizabeth M.

    2012-01-01

    Objective: There are presently almost no empirically validated treatments for adolescents with ADHD. However, in childhood, behavioral treatments for ADHD typically include behavioral parent training, classroom interventions, and intensive child-directed interventions. Method: The present investigation examines treatment gains following an 8-week…

  10. Treatment Response to an Intensive Summer Treatment Program for Adolescents with ADHD

    ERIC Educational Resources Information Center

    Sibley, Margaret H.; Smith, Bradley H.; Evans, Steven W.; Pelham, William E.; Gnagy, Elizabeth M.

    2012-01-01

    Objective: There are presently almost no empirically validated treatments for adolescents with ADHD. However, in childhood, behavioral treatments for ADHD typically include behavioral parent training, classroom interventions, and intensive child-directed interventions. Method: The present investigation examines treatment gains following an 8-week…

  11. Predicting post-traumatic stress disorder treatment response in refugees: Multilevel analysis.

    PubMed

    Haagen, Joris F G; Ter Heide, F Jackie June; Mooren, Trudy M; Knipscheer, Jeroen W; Kleber, Rolf J

    2017-03-01

    Given the recent peak in refugee numbers and refugees' high odds of developing post-traumatic stress disorder (PTSD), finding ways to alleviate PTSD in refugees is of vital importance. However, there are major differences in PTSD treatment response between refugees, the determinants of which are largely unknown. This study aimed at improving PTSD treatment for adult refugees by identifying PTSD treatment response predictors. A prospective longitudinal multilevel modelling design was used to predict PTSD severity scores over time. We analysed data from a randomized controlled trial with pre-, post-, and follow-up measurements of the safety and efficacy of eye movement desensitization and reprocessing and stabilization in asylum seekers and refugees suffering from PTSD. Lack of refugee status, comorbid depression, demographic, trauma-related and treatment-related variables were analysed as potential predictors of PTSD treatment outcome. Treatment outcome data from 72 participants were used. The presence (B = 6.5, p = .03) and severity (B = 6.3, p < .01) of a pre-treatment depressive disorder predicted poor treatment response and explained 39% of the variance between individuals. Refugee patients who suffer from PTSD and severe comorbid depression benefit less from treatment aimed at alleviating PTSD. Results highlight the need for treatment adaptations for PTSD and comorbid severe depression in traumatized refugees, including testing whether initial targeting of severe depressive symptoms increases PTSD treatment effectiveness. There are differences in post-traumatic stress disorder (PTSD) treatment response between traumatized refugees. Comorbid depressive disorder and depression severity predict poor PTSD response. Refugees with PTSD and severe depression may not benefit from PTSD treatment. Targeting comorbid severe depression before PTSD treatment is warranted. This study did not correct for multiple hypothesis testing. Comorbid depression may

  12. Mitochondria in the striatum of subjects with schizophrenia: relationship to treatment response.

    PubMed

    Somerville, Shahza M; Lahti, Adrienne C; Conley, Robert R; Roberts, Rosalinda C

    2011-03-01

    Schizophrenia (SZ) is a severe mental illness with neuropathology in many regions, including the striatum. The typical symptoms of this disease are psychosis (such as hallucinations and delusions), cognitive impairments, and the deficit syndrome. Not all patients respond to treatment and, in those who do, only psychotic symptoms are improved. Imaging studies support a biological distinction between treatment response and resistance, but postmortem examinations of this issue are rare. This study tests the hypotheses that abnormalities in mitochondria, the energy producing organelles in the cell, may correlate with treatment response. Postmortem striatal tissue was obtained from the Maryland Brain Collection. The density of mitochondria (in various neuropil compartments) and the number of mitochondria per synapse (all types of synapses combined) were tallied using electron microscopy and stereology in striatum from SZ subjects (rated treatment responsive or not) and normal controls. The number of mitochondria per synapse was significantly different among groups for both the caudate nucleus (P < 0.025) and putamen (P < 0.002). Compared to controls, treatment-responsive SZ subjects had a 37-43% decrease in the number of mitochondria per synapse in the caudate nucleus and putamen. In the putamen, treatment-responsive subjects also had decreases in this measure compared to treatment-resistant subjects (34%). Our results provide further support for a biological distinction between treatment response and treatment resistance in SZ. Because treatment responders have fewer mitochondria per synapse than controls, although the treatment-resistant subjects have similar results to that of controls, fewer mitochondria per synapse may be related to treatment response.

  13. Significance of "Deqi" response in acupuncture treatment: myth or reality.

    PubMed

    Zhou, Wei; Benharash, Peyman

    2014-08-01

    Acupuncture has been practiced in China for over 2000 years to treat a variety of diseases based on the "meridian theory," as described in the "Yellow Emperor's Classics of Internal Medicine." Deqi refers to the excitation of qi or vital energy inside meridians by acupuncture needle stimulation. Patients often experience multidimensional and intense needling sensations such as numbness, soreness, distention, heaviness, dull pain, and sharp pain during acupuncture stimulation. Deqi is considered as an important parameter in the process of achieving therapeutic effectiveness in acupuncture treatment. Understanding this phenomenon from neurophysiological aspects is important for clinical practice and enables practitioners to perform quantitative acupuncture evaluation to obtain a reliable prognosis of acupuncture treatment. This review paper describes our current knowledge and understanding of Deqi from a physiological aspect. Copyright © 2014. Published by Elsevier B.V.

  14. Parsing placebo treatments: a response to Barnhill and Miller.

    PubMed

    Glackin, Shane Nicholas

    2016-10-01

    Anne Barnhill and Franklin Miller dispute my claim that the prescriptions of placebo treatments to patients are not typically deceptive, and do not typically violate the patients' informed consent. However, Barnhill and Miller seriously mischaracterise my position in two ways, as well as failing to show that the procedure I discuss requires a physician to act wrongfully in deceiving her patient. Accordingly, I find their argument unpersuasive.

  15. Temetex in the treatment of steroid-responsive dermatoses.

    PubMed

    Bergson, V S; Franklin, W H

    1977-01-01

    Five hundred and seventy-five patients with various steroid-responsive dermatoses were studied for up to six weeks in eighty-eight separate general practices using a new topical corticosteroid. Temetex (diflucortolone valerate 0-1%). It was concluded that Temetex is both effective and well tolerated in a wide variety of conditions, especially eczema and psoriasis. It was also shown that a large-scale general practice trial can be carried out efficiently with a very high compliance rate.

  16. Temporal Treatment of a Thermal Response for Defect Depth Estimation

    NASA Technical Reports Server (NTRS)

    Plotnikov, Y. A.; Winfree, W. P.

    2004-01-01

    Transient thermography, which employs pulse surface heating of an inspected component followed by acquisition of the thermal decay stage, is gaining wider acceptance as a result of its remoteness and rapidness. Flaws in the component s material may induce a thermal contrast in surface thermograms. An important issue in transient thermography is estimating the depth of a subsurface flaw from the thermal response. This improves the quantitative ability of the thermal evaluation: from one scan it is possible to locate regions of anomalies in thickness (caused by corrosion) and estimate the implications of the flaw on the integrity of the structure. Our research focuses on thick composite aircraft components. A long square heating pulse and several minutes observation period are required to receive an adequate thermal response from such a component. Application of various time-related informative parameters of the thermal response for depth estimation is discussed. A three-dimensional finite difference model of heat propagation in solids in Cartesian coordinates is used to simulate the thermographic process. Typical physical properties of polymer graphite composites are assumed for the model.

  17. Acclimation responses of Arabidopsis thaliana to sustained phosphite treatments

    PubMed Central

    Berkowitz, Oliver

    2013-01-01

    Phosphite () induces a range of physiological and developmental responses in plants by disturbing the homeostasis of the macronutrient phosphate. Because of its close structural resemblance to phosphate, phosphite impairs the sensing, membrane transport, and subcellular compartmentation of phosphate. In addition, phosphite induces plant defence responses by an as yet unknown mode of action. In this study, the acclimation of Arabidopsis thaliana plants to a sustained phosphite supply in the growth medium was investigated and compared with plants growing under varying phosphate supplies. Unlike phosphate, phosphite did not suppress the formation of lateral roots in several Arabidopsis accessions. In addition, the expression of well-documented phosphate-starvation-induced genes, such as miRNA399d and At4, was not repressed by phosphite accumulation, whilst the induction of PHT1;1 and PAP1 was accentuated. Thus, a mimicking of phosphate by phosphite was not observed for these classical phosphate-starvation responses. Metabolomic analysis of phosphite-treated plants showed changes in several metabolite pools, most prominently those of aspartate, asparagine, glutamate, and serine. These alterations in amino acid pools provide novel insights for the understanding of phosphite-induced pathogen resistance. PMID:23404904

  18. White-matter connectivity related to paliperidone treatment response in patients with schizophrenia.

    PubMed

    Kim, Min-Kyoung; Kim, Borah; Lee, Kang Soo; Kim, Chan Mo; Bang, Seong Yun; Choi, Tai Kiu; Lee, Sang-Hyuk

    2016-03-01

    The objective of this study was to examine whether white-matter (WM) connectivity of patients with schizophrenia at early stage of treatment is related to treatment response after paliperidone extended-release (ER) treatment. Forty-one patients with schizophrenia and 17 age- and sex-matched healthy control subjects were included in this study. Brain magnetic resonance scans at 3 Tesla were conducted at early stage of treatment. Voxel-wise statistical analysis of the fractional anisotropy (FA) data was performed using Tract-Based Spatial Statistics. At baseline and eight weeks after paliperidone treatment, patients were assessed using the Positive and Negative Syndrome Scale, the Scale for the Assessment of Positive Symptoms and the Scale for the Assessment of Negative Symptoms. Among the patients with schizophrenia, the FA values of the corpus callosum, corona radiata, internal capsule, external capsule, superior longitudinal fasciculus and fronto-temporal WM regions showed significant negative correlations with scores of the treatment response. The current study suggests that the treatment response after paliperidone ER treatment may be associated with the fronto-temporo-limbic WM connectivity at early stage of treatment in patients with schizophrenia, and it could be used as a predictor of treatment response to paliperidone ER treatment after studies with large samples verify these results.

  19. Drinking water treatment response following a Colorado wildfire.

    PubMed

    Hohner, Amanda K; Cawley, Kaelin; Oropeza, Jill; Summers, R Scott; Rosario-Ortiz, Fernando L

    2016-11-15

    Wildfires can greatly alter the vegetation, soils, and hydrologic processes of watersheds serving as drinking water supplies, which may negatively influence source water quality and treatment. To address wildfire impacts on treatment, a drinking water intake below a burned watershed and an upstream, unburned reference site were monitored following the High Park wildfire (2012) in the Cache la Poudre watershed of northern Colorado, USA. Turbidity, nutrients, dissolved organic matter (DOM) character, coagulation treatability, and disinfection byproduct formation were evaluated and compared to pre-fire data. Post-fire paired spatial differences between the treatment plant intake and reference site for turbidity, nitrogen, and phosphorus increased by an order of magnitude compared to pre-fire differences. Fluorescence index (FI) values were significantly higher at the intake compared to the reference site (Δ = 0.04), and higher than pre-fire years, suggesting the wildfire altered the DOM character of the river. Total trihalomethane (TTHM) and haloacetonitrile (HAN4) formation at the intake were 10.1 μg L(-1) and 0.91 μg L(-1) higher than the reference site. Post-fire water was amenable to conventional treatment at a 10 mg L(-1) higher average alum dose than reference samples. The intake was also monitored following rainstorms. Post-rainstorm samples showed the maximum observed FI values (1.52), HAN4 (3.4 μg mgC(-1)) and chloropicrin formation yields (3.6 μg mgC(-1)), whereas TTHM and haloacetic acid yields were not elevated. Several post-rainstorm samples presented treatment challenges, and even at high alum doses (65 mg L(-1)), showed minimal dissolved organic carbon removal (<10%). The degraded water quality of the post-rainstorm samples is likely attributed to the combined effects of runoff from precipitation and greater erosion following wildfire. Wildfire impacts cannot be separated from rainfall effects due to the lack of post-rainstorm samples from

  20. Managing inadequate responses to frontline treatment of chronic myeloid leukemia: a case-based review.

    PubMed

    Bixby, Dale L

    2013-05-01

    The tyrosine kinase inhibitors (TKIs) imatinib, nilotinib, and dasatinib are the standard of care for treating patients with newly diagnosed chronic-phase chronic myeloid leukemia (CML). Compared with interferon-based treatment, the previous standard of care, imatinib is associated with significantly higher cytogenetic response rates and prolonged overall survival. Nilotinib and dasatinib, both newer and more potent TKIs, significantly improve cytogenetic and molecular response rates compared with imatinib. Despite significant advances in CML treatment enabled by the TKIs, a fraction of patients who receive frontline treatment with a TKI demonstrate inadequate response. The reasons for this vary, but in many cases, inadequate response can be attributed to non-adherence to the treatment regimen, intolerance to the drug, intrinsic or acquired resistance to the drug, or a combination of reasons. More often than not, strategies to improve response necessitate a change in treatment plan, either a dose adjustment or a switch to an alternate drug, particularly in the case of drug intolerance or drug resistance. Improved physician-patient communication and patient education are effective strategies to address issues relating to adherence and intolerance. Because inadequate response to TKI treatment correlates with poor long-term outcomes, it is imperative that patients who experience intolerance or who fail to achieve appropriate responses are carefully evaluated so that appropriate treatment modifications can be made to maximize the likelihood of positive long-term outcome. Copyright © 2012. Published by Elsevier Ltd.

  1. Atypical depressive symptoms as a predictor of treatment response to exercise in Major Depressive Disorder.

    PubMed

    Rethorst, Chad D; Tu, Jian; Carmody, Thomas J; Greer, Tracy L; Trivedi, Madhukar H

    2016-08-01

    Effective treatment of Major Depressive Disorder (MDD) will require the development of alternative treatments and the ability for clinicians to match patients with the treatment likely to produce the greatest effect. We examined atypical depression subtype as a predictor of treatment response to aerobic exercise augmentation in persons with non-remitted MDD. Our results revealed a small-to-moderate effect, particularly in a group assigned to high-dose exercise (semi-partial eta-squared =0.0335, p=0.0735), indicating that those with atypical depression tended to have larger treatment response to exercise. Through this hypothesis-generating analysis, we indicate the need for research to examine depression subtype, along with other demographic, clinical and biological factors as predictors of treatment response to exercise.

  2. Stereotactic body radiation therapy of liver tumors: post-treatment appearances and evaluation of treatment response: a pictorial review.

    PubMed

    Haddad, Mustafa M; Merrell, Kenneth W; Hallemeier, Christopher L; Johnson, Geoffrey B; Mounajjed, Taofic; Olivier, Kenneth R; Fidler, Jeff L; Venkatesh, Sudhakar K

    2016-10-01

    Stereotactic body radiation therapy (SBRT) is a noninvasive treatment technique for selected patients with primary liver tumors and liver-confined oligometastatic disease. Recently, SBRT has emerged as an alternative treatment option in non-surgical candidates and in whom percutaneous treatment methods are not possible or contraindicated. The experience with SBRT continues to grow. There are currently no imaging guidelines for assessment of tumor response and follow-up schedule following SBRT. SBRT produces characteristic radiation-induced changes in the treated tumor and surrounding liver parenchyma. Knowledge of these changes is essential in the interpretation of follow-up imaging and assessment of treatment response. In this review, we will describe the CT, MRI, and PET imaging findings following SBRT of both the targeted liver tumor and surrounding hepatic parenchyma.

  3. Rapid response to eating disorder treatment: A systematic review and meta-analysis.

    PubMed

    Linardon, Jake; Brennan, Leah; de la Piedad Garcia, Xochitl

    2016-10-01

    This review aimed to (a) examine the effects of rapid response on behavioral, cognitive, and weight-gain outcomes across the eating disorders, (b) determine whether diagnosis, treatment modality, the type of rapid response (changes in disordered eating cognitions or behaviors), or the type of behavioral outcome moderated this effect, and (c) identify factors that predict a rapid response. Thirty-four articles met inclusion criteria from six databases. End of treatment and follow-up outcomes were divided into three categories: Behavioral (binge eating/purging), cognitive (EDE global scores), and weight gain. Average weighted effect sizes(r) were calculated. Rapid response strongly predicted better end of treatment and follow-up cognitive and behavioral outcomes. Moderator analyses showed that the effect size for rapid response on behavioral outcomes was larger when studies included both binge eating and purging (as opposed to just binge eating) as a behavioral outcome. Diagnosis, treatment modality, and the type of rapid response experienced did not moderate the relationship between early response and outcome. The evidence for weight gain was mixed. None of the baseline variables analyzed (eating disorder psychopathology, demographics, BMI, and depression scores) predicted a rapid response. As there is a solid evidence base supporting the prognostic importance of rapid response, the focus should shift toward identifying the within-treatment mechanisms that predict a rapid response so that the effectiveness of eating disorder treatment can be improved. There is a need for future research to use theories of eating disorders as a guide to assess within-treatment predictors of rapid response. © 2016 Wiley Periodicals, Inc. Int J Eat Disord 2016; 49:905-919. © 2016 Wiley Periodicals, Inc.

  4. Smoking and Opioid Detoxification: Behavioral Changes and Response to Treatment

    PubMed Central

    2013-01-01

    Introduction: The relevance of tobacco use in opioid addiction (OA) has generated a demand for available and more effective interventions. Thus, further analysis of less explored nicotine–opioid clinical interactions is warranted. Methods: A post-hoc analysis of OA participants in a double-blind, randomized very low dose naltrexone (VLNTX) inpatient detoxification trial evaluated measures of opioid withdrawal and tobacco use. Intreatment smokers were compared with nonsmokers, or smokers who were not allowed to smoke. Results: A total of 141 (81%) of 174 OA participants were smokers, all nicotine-dependent. Inpatient smoking was a predictor of opioid withdrawal discomfort. Intreatment smokers (n = 96) showed significantly higher opioid craving (F = 3.7, p < .001) and lower detoxification completion rate (χ2 = 7.9, p < .02) compared with smokers who were not allowed to smoke (n = 45) or nonsmokers (n = 33). Smoking during treatment was associated with more elevated cigarette craving during detoxification (F = 4.1, p < .001) and a higher number of cigarettes smoked at follow-up (F = 3.6, p < .02). Among intreatment smokers, VLNTX addition to methadone taper was effective in easing opioid withdrawal and craving more than other treatments, whereas the combination VLNTX–clonidine was associated with significantly reduced cigarette craving and smoking during detoxification. Conclusions: Failure to address tobacco use may negatively affect pharmacologically managed opioid discontinuation. Opioid detoxification may offer a window of opportunity to expand smoking cessation treatment, hence improving OA outcomes. The observed effects support testing of VLNTX–clonidine in smoking cessation trials among individuals with or without substance abuse. PMID:23572466

  5. Acute promyelocytic leukemia: new issues on pathogenesis and treatment response.

    PubMed

    Vitoux, Dominique; Nasr, Rihab; de The, Hugues

    2007-01-01

    Pathogenesis of acute promyelocytic leukemia appears to be one of the best understood among human malignancies. The ability of retinoic acid (RA) and arsenic trioxide to directly target the oncogenic promyelocytic leukemia-retinoic receptor A (PML-RARA) fusion protein also made this disease the first model for oncogene-targeted therapies. A set of recent data has significantly increased the complexity of our view of acute promyelocytic leukemia pathogenesis, as well as of therapeutic response. This review summarizes and discusses these findings, which yield novels questions and models.

  6. Wood preserving waste-contaminated soil: Treatment and toxicity response

    SciTech Connect

    Huling, S.G.; Pope, D.F.; Matthews, J.E.; Sims, J.L.; Sims, R.C.; Sorensen, D.L.

    1995-12-31

    Soils contaminated with pentachlorophenol (PCP) and creosote were treated without bioaugmentation at field scale in tow 1-acre land treatment units (LTUs) at Libby, Montana. The concentration of indicator compounds of treatment performance, i.e., PCP, pyrene, total carcinogenic polycyclic aromatic hydrocarbons (TCPAHs) were monitored in the soil by taking both composited and discrete soil samples. A statistically significant decrease in PCP, pyrene, and TCPAH concentration occurred at field scale, and first-order degradation rate kinetics, from discrete and composited soil samples, satisfactorily represented the chemical loss for these compounds. Detoxification, as measured by the Microtox{trademark} assay, occurred in the soil; and toxicity reduction corresponded with PCP, pyrene, and TCPAH disappearance. No increase in toxicity in the lower treated soil layers (lifts) of the LTUs was observed with time, while the upper, more recently applied lifts were highly contaminated and toxic. This indicated that vertical migration of soluble contaminants had little effect on microbial activity in lower lifts of treated soil.

  7. Performance Variability as a Predictor of Response to Aphasia Treatment.

    PubMed

    Duncan, E Susan; Schmah, Tanya; Small, Steven L

    2016-10-01

    Performance variability in individuals with aphasia is typically regarded as a nuisance factor complicating assessment and treatment. We present the alternative hypothesis that intraindividual variability represents a fundamental characteristic of an individual's functioning and an important biomarker for therapeutic selection and prognosis. A total of 19 individuals with chronic aphasia participated in a 6-week trial of imitation-based speech therapy. We assessed improvement both on overall language functioning and repetition ability. Furthermore, we determined which pretreatment variables best predicted improvement on the repetition test. Significant gains were made on the Western Aphasia Battery-Revised (WAB) Aphasia Quotient, Cortical Quotient, and 2 subtests as well as on a separate repetition test. Using stepwise regression, we found that pretreatment intraindividual variability was the only predictor of improvement in performance on the repetition test, with greater pretreatment variability predicting greater improvement. Furthermore, the degree of reduction in this variability over the course of treatment was positively correlated with the degree of improvement. Intraindividual variability may be indicative of potential for improvement on a given task, with more uniform performance suggesting functioning at or near peak potential. © The Author(s) 2016.

  8. Microglial responses to amyloid β peptide opsonization and indomethacin treatment

    PubMed Central

    Strohmeyer, Ronald; Kovelowski, Carl J; Mastroeni, Diego; Leonard, Brian; Grover, Andrew; Rogers, Joseph

    2005-01-01

    Background Recent studies have suggested that passive or active immunization with anti-amyloid β peptide (Aβ) antibodies may enhance microglial clearance of Aβ deposits from the brain. However, in a human clinical trial, several patients developed secondary inflammatory responses in brain that were sufficient to halt the study. Methods We have used an in vitro culture system to model the responses of microglia, derived from rapid autopsies of Alzheimer's disease patients, to Aβ deposits. Results Opsonization of the deposits with anti-Aβ IgG 6E10 enhanced microglial chemotaxis to and phagocytosis of Aβ, as well as exacerbated microglial secretion of the pro-inflammatory cytokines TNF-α and IL-6. Indomethacin, a common nonsteroidal anti-inflammatory drug (NSAID), had no effect on microglial chemotaxis or phagocytosis, but did significantly inhibit the enhanced production of IL-6 after Aβ opsonization. Conclusion These results are consistent with well known, differential NSAID actions on immune cell functions, and suggest that concurrent NSAID administration might serve as a useful adjunct to Aβ immunization, permitting unfettered clearance of Aβ while dampening secondary, inflammation-related adverse events. PMID:16111494

  9. A thermo-responsive protein treatment for dry eyes

    PubMed Central

    Wang, Wan; Jashnani, Aarti; Aluri, Suhaas R.; Gustafson, Joshua A.; Hsueh, Pang-Yu; Yarber, Frances; McKown, Robert L.; Laurie, Gordon W.; Hamm-Alvarez, Sarah F.; MacKay, J. Andrew

    2015-01-01

    Millions of Americans suffer from dry eye disease, and there are few effective therapies capable of treating these patients. A decade ago, an abundant protein component of human tears was discovered and named lacritin(Lacrt). Lacrt has prosecretory activity in the lacrimal gland and mitogenic activity at the corneal epithelium. Similar to other proteins placed on the ocular surface, the durability of its effect is limited by rapid tear turnover. Motivated by the rationale that a thermo-responsive coacervate containing Lacrt would have better retention upon administration, we have constructed and tested the activity of a thermo-responsive Lacrt fused to an Elastin-like polypeptide (ELP). Inspired from the human tropoelastin protein, ELP protein polymers reversibly phase separate into viscous coacervates above a tunable transition temperature. This fusion construct exhibited the prosecretory function of native Lacrt as illustrated by its ability to stimulate β-hexosaminidase secretion from primary rabbit lacrimal gland acinar cells. It also increased tear secretion from non-obese diabetic (NOD) mice, a model of autoimmune dacryoadenitis, when administered via intra-lacrimal injection. Lacrt ELP fusion proteins undergo temperature-mediated assembly to form a depot inside the lacrimal gland. We propose that these Lacrt ELP fusion proteins represent a potential therapy for dry eye disease and the strategy of ELP-mediated phase separation may have applicability to other diseases of the ocular surface. PMID:25481446

  10. Bench to Bedside: Understanding Symptom Response to Acupuncture Treatment and Designing a Successful Acupuncture Treatment Program

    DTIC Science & Technology

    2016-10-01

    funded project “The Effectiveness of Acupuncture in the Treatment of Gulf War Illness ” (W81 XWH). Objectives: This application has two objectives...We have two papers in manuscript development now: 1) Baseline Characteristics of a Sample of Veterans with Gulf War Illness , 2) Complex Baseline...Predictors of Symptom Improvement Following Acupuncture Treatment of Gulf War Illness . Lastly information on real dose of treatment used for each patient

  11. Dispositional optimism, trait anxiety, and coping: unique or shared effects on biological response to fertility treatment?

    PubMed

    Lancastle, Deborah; Boivin, Jacky

    2005-03-01

    The aim of this study was to examine the unique and shared predictive power of psychological variables on reproductive physical health. Three months before fertility treatment, 97 women completed measures of dispositional optimism, trait anxiety, and coping. Information about biological response to treatment (e.g., estradiol level) was collected from medical charts after treatment. Structural equation modeling showed that measured psychological variables were all significant indicators of a single latent construct and that this construct was a better predictor of biological response to treatment than was any individual predictor. This research contributes to evidence suggesting that the health benefits of dispositional optimism are due to its shared variance with neuroticism.

  12. Gene expression biomarkers of response to citalopram treatment in major depressive disorder

    PubMed Central

    Mamdani, F; Berlim, M T; Beaulieu, M-M; Labbe, A; Merette, C; Turecki, G

    2011-01-01

    There is significant variability in antidepressant treatment outcome, with ∼30–40% of patients with major depressive disorder (MDD) not presenting with adequate response even following several trials. To identify potential biomarkers of response, we investigated peripheral gene expression patterns of response to antidepressant treatment in MDD. We did this using Affymetrix HG-U133 Plus2 microarrays in blood samples, from untreated individuals with MDD (N=63) ascertained at a community outpatient clinic, pre and post 8-week treatment with citalopram, and used a regression model to assess the impact of gene expression differences on antidepressant response. We carried out technical validation of significant probesets by quantitative reverse transcriptase PCR and conducted central nervous system follow-up of the most significant result in post-mortem brain samples from 15 subjects who died during a current MDD episode and 11 sudden-death controls. A total of 32 probesets were differentially expressed according to response to citalopram treatment following false discovery rate correction. Interferon regulatory factor 7 (IRF7) was the most significant differentially expressed gene and its expression was upregulated by citalopram treatment in individuals who responded to treatment. We found these results to be concordant with our observation of decreased expression of IRF7 in the prefrontal cortex of MDDs with negative toxicological evidence for antidepressant treatment at the time of death. These findings point to IRF7 as a gene of interest in studies investigating genomic factors associated with antidepressant response. PMID:22832429

  13. Treatment predictors of a sustained virologic response in hepatitis B and C.

    PubMed

    Kau, Annika; Vermehren, Johannes; Sarrazin, Christoph

    2008-10-01

    Treatment predictors are important tools for the management of therapy in patients with chronic hepatitis B and C virus (HBV, HCV) infection. In chronic hepatitis B, several pretreatment parameters have been identified for prediction of virologic response to interferon alfa-based antiviral therapies or treatment with polymerase inhibitors. In interferon alfa and pegylated interferon alfa-treated patients, low baseline HBV DNA concentrations, HBV genotype A (B), and high baseline ALT levels are significantly associated with treatment response. In patients treated with nucleos(t)ide analogues, low baseline HBV DNA but not viral genotype is positively associated with virologic response. During treatment the best predictor of response is HBV DNA kinetics. Early viral suppression is associated with favourable virologic response and reduced risk for subsequent resistance mutations. For the current standard treatment with pegylated interferon alfa and ribavirin in patients with chronic hepatitis C, infection with HCV genotypes 2 and 3, baseline viral load below 400,000-800,000 IU/ml, Asian and Caucasian ethnicity, younger age, low GGT levels, absence of advanced fibrosis/cirrhosis, and absence of steatosis in the liver have been identified as independent pretreatment predictors of a sustained virologic response. After initiation of treatment, initial viral decline with undetectable HCV-RNA at week 4 of therapy (RVR) is the best predictor of sustained virologic response independent of HCV genotype.

  14. Treatment responsive Holmes tremor: case report and literature review

    PubMed Central

    Alqwaifly, Mohammed

    2016-01-01

    Holmes tremor is a rare symptomatic movement disorder, characterized by a combination of resting, postural, and action tremors. It is usually caused by lesions involving the brainstem, thalamus, and cerebellum. It is often difficult to treat, many medications have been used with varying degrees of success. It may respond to stereotactic thalamotomy and deep brain stimulation in ventralis intermedius nucleus. Here I report a case of Holmes tremor secondary to multiple sclerosis that treated with L-dopa/carpidopa and showed marked improvement. A relevant literature search was performed, using PubMed for Holmes tremor as labelled in the literature. I included all patients diagnosed with Holmes tremor who responded to medical treatment. I found 27 cases, which are summarized in this review. This report describes a patient with Holmes tremor, who responded very well to Levodopa. This outcome suggests that Levodopa should be considered in the initial management of Holmes tremor. PMID:27833521

  15. Novel Approaches to Thyroid Cancer Treatment and Response Assessment

    PubMed Central

    Grewal, Ravinder K.; Ho, Alan; Schöder, Heiko

    2015-01-01

    The incidence of thyroid cancer has been on the rise. After total thyroidectomy of well differentiated thyroid tumors with intermediate or high-risk features on pathology, radioiodine remains one of the mainstays as the standard therapy for thyroid remnant ablation as well as treatment of metastatic disease. SPECT/CT, a relatively newer modality, has shown to play a pivotal role predominantly in the post-therapy setting by changing the risk stratification of patients with thyroid cancer. In the case of radioiodine failure, other modalities such as FDG PET/CT have been shown to provide prognostic information in terms of metabolic activity and external beam radiation therapy, thereby playing a role in disease management. The role of newer redifferentiation drugs has been evaluated with the use of I-124 PET/CT. PMID:26897715

  16. A case of erythromelalgia: good response to treatment with gabapentin.

    PubMed

    Ceyhan, Ali Murat; Gurses, Ipek; Yildirim, Mehmet; Akkaya, Vahide Baysal

    2010-05-01

    Erythromelalgia is a rare chronic disorder characterized by intense burning pain, redness, swelling and increased skin temperature. It occurs primarily in the feet, but may also involve the hands, face and ears. Warming of the extremity or placing and maintaining the extremity in a dependent position can exacerbate symptoms. These symptoms are typically refractory to various medications, but are relieved by elevation or exposure to cold. Although a specific therapy is not available for erythromelalgia yet, several treatment modalities may be used as therapeutic options, including: aspirin, indomethacine beta-blockers, calcium channel antagonists, misoprostol, diltiazem, tricyclic antidepressants, serotonin reuptake inhibitors and number of more aggressive procedures--such as intravenous lidocaine, epidural anaesthesia, intrathecal opiates and sympathetic ganglion blockade. There are very few reports in the literature of gabapentin successfully treating erythromelalgia. Here, the authors report a case of primary erythromelalgia in a 20-year-old woman responding to gabapentin therapy.

  17. Unfolded protein response, treatment and CMT1B

    PubMed Central

    Bai, Yunhong; Patzko, Agnes; Shy, Michael E.

    2013-01-01

    CMT1B is the second most frequent autosomal dominant inherited neuropathy and is caused by assorted mutations of the myelin protein zero (MPZ) gene. MPZ mutations cause neuropathy gain of function mechanisms that are largely independent MPZs normal role of mediating myelin compaction. Whether there are only a few or multiple pathogenic mechanisms that cause CMT1B is unknown. Arg98Cys and Ser63Del MPZ are two CMT1B causing mutations that have been shown to cause neuropathy in mice at least in part by activating the unfolded protein response (UPR). We have recently treated Arg98Cys mice with derivatives of curcumin that improved the neuropathy and reduced UPR activation.1 Future studies will address whether manipulating the UPR will be a common or rare strategy for treating CMT1B or other forms of inherited neuropathies. PMID:25002989

  18. Upper esophageal sphincter abnormalities are strongly predictive of treatment response in patients with achalasia

    PubMed Central

    Mathews, Simon C; Ciarleglio, Maria; Chavez, Yamile Haito; Clarke, John O; Stein, Ellen; Chander Roland, Bani

    2014-01-01

    AIM: To investigate the relationship between upper esophageal sphincter abnormalities achalasia treatment METHODS: We performed a retrospective study of 41 consecutive patients referred for high resolution esophageal manometry with a final manometric diagnosis of achalasia. Patients were sub-divided by presence or absence of Upper esophageal sphincter (UES) abnormality, and clinical and manometric profiles were compared. Correlation between UES abnormality and sub-type (i.e., hypertensive, hypotensive or impaired relaxation) and a number of variables, including qualitative treatment response, achalasia sub-type, co-morbid medical illness, psychiatric illness, surgical history, dominant presenting symptom, treatment type, age and gender were also evaluated. RESULTS: Among all 41 patients, 24 (58.54%) had a UES abnormality present. There were no significant differences between the groups in terms of age, gender or any other clinical or demographic profiles. Among those with UES abnormalities, the majority were either hypertensive (41.67%) or had impaired relaxation (37.5%) as compared to hypotensive (20.83%), although this did not reach statistical significance (P = 0.42). There was no specific association between treatment response and treatment type received; however, there was a significant association between UES abnormalities and treatment response. In patients with achalasia and concomitant UES abnormalities, 87.5% had poor treatment response, while only 12.5% had favorable response. In contrast, in patients with achalasia and no UES abnormalities, the majority (78.57%) had good treatment response, as compared to 21.43% with poor treatment response (P = 0.0001). After controlling for achalasia sub-type, those with UES abnormality had 26 times greater odds of poor treatment response than those with no UES abnormality (P = 0.009). Similarly, after controlling for treatment type, those with UES abnormality had 13.9 times greater odds of poor treatment response

  19. Clinical utility of C-reactive protein to predict treatment response during cystic fibrosis pulmonary exacerbations

    PubMed Central

    Sharma, Ashutosh; Kirkpatrick, Gordon; Chen, Virginia; Skolnik, Kate; Hollander, Zsuzsanna; Wilcox, Pearce; Quon, Bradley S.

    2017-01-01

    Rationale C-reactive protein (CRP) is a systemic marker of inflammation that correlates with disease status in cystic fibrosis (CF). The clinical utility of CRP measurement to guide pulmonary exacerbation (PEx) treatment decisions remains uncertain. Objectives To determine whether monitoring CRP during PEx treatment can be used to predict treatment response. We hypothesized that early changes in CRP can be used to predict treatment response. Methods We reviewed all PEx events requiring hospitalization for intravenous (IV) antibiotics over 2 years at our institution. 83 PEx events met our eligibility criteria. CRP levels from admission to day 5 were evaluated to predict treatment non-response, using a modified version of a prior published composite definition. CRP was also evaluated to predict time until next exacerbation (TUNE). Measurements and main results 53% of 83 PEx events were classified as treatment non-response. Paradoxically, 24% of PEx events were characterized by a ≥ 50% increase in CRP levels within the first five days of treatment. Absolute change in CRP from admission to day 5 was not associated with treatment non-response (p = 0.58). Adjusted for FEV1% predicted, admission log10 CRP was associated with treatment non-response (OR: 2.39; 95% CI: 1.14 to 5.91; p = 0.03) and shorter TUNE (HR: 1.60; 95% CI: 1.13 to 2.27; p = 0.008). The area under the receiver operating characteristics (ROC) curve of admission CRP to predict treatment non-response was 0.72 (95% CI 0.61–0.83; p<0.001). 23% of PEx events were characterized by an admission CRP of > 75 mg/L with a specificity of 90% for treatment non-response. Conclusions Admission CRP predicts treatment non-response and time until next exacerbation. A very elevated admission CRP (>75mg/L) is highly specific for treatment non-response and might be used to target high-risk patients for future interventional studies aimed at improving exacerbation outcomes. PMID:28178305

  20. Peer-Nominated Deviant Talk within Residential Treatment: Individual and Group Influences on Treatment Response

    ERIC Educational Resources Information Center

    Zakriski, Audrey L.; Wright, Jack C.; Cardoos, Stephanie L.

    2011-01-01

    This research examined deviant talk during summer residential treatment using peer nominations and extensive field observations. Participants were 239 youth (M age = 12.62, SD = 2.60; 67% male), nested in 26 treatment groups. Deviant talk was present in this setting, showed individual differences, and increased over time, especially for younger…

  1. Peer-Nominated Deviant Talk within Residential Treatment: Individual and Group Influences on Treatment Response

    ERIC Educational Resources Information Center

    Zakriski, Audrey L.; Wright, Jack C.; Cardoos, Stephanie L.

    2011-01-01

    This research examined deviant talk during summer residential treatment using peer nominations and extensive field observations. Participants were 239 youth (M age = 12.62, SD = 2.60; 67% male), nested in 26 treatment groups. Deviant talk was present in this setting, showed individual differences, and increased over time, especially for younger…

  2. Interpersonal impacts mediate the association between personality and treatment response in major depression.

    PubMed

    Dermody, Sarah S; Quilty, Lena C; Bagby, R Michael

    2016-07-01

    Personality, as characterized by the Five-Factor Model, predicts response to psychotherapy for depression. To explain how personality impacts treatment response, the present study investigated patient and therapist interpersonal processes in treatment sessions as an explanatory pathway. A clinical trial was conducted in which 103 outpatients (mean age: 41.17 years, 65% female) with primary major depressive disorder completed 16-20 weeks of cognitive-behavioral or interpersonal therapy. Before treatment, patients completed the Revised NEO Personality Inventory to assess personality domains (neuroticism, extraversion, openness-to-experience, agreeableness, and conscientiousness). After 3 and 13 weeks, patient interpersonal behavior was rated by the therapist and vice versa to determine levels of patient and therapist communal and agentic behaviors. Depression levels were measured before and after treatment. Structural equation modeling supported that patients' interpersonal behavior during therapy mediated the associations between pretreatment personality and depression treatment outcome. Specifically, extraversion, conscientiousness, and neuroticism (inverse) predicted higher levels of patient communion throughout treatment, which was in turn associated with improved treatment outcomes. Furthermore, patient agreeableness was inversely associated with agency throughout treatment, which was linked to poorer treatment response. Therapist interpersonal behavior was not a significant mediator. Results suggest that patient interpersonal behavior during treatment may be one way that patient personality impacts clinical outcomes in depression. Results underscore the clinical utility of Five-Factor Model domains in treatment process and outcome. (PsycINFO Database Record

  3. Growth Response From Herbicide, Prescribed Fire, and Fertilizer Treatments in Midrotational Loblolly Pine: Fire-Year Response

    Treesearch

    Mary Michelle Barnett; Sandra Rideout; Brian P. Oswald; Kenneth W. Farrish; Hans M. Williams

    2002-01-01

    This study was initiated to determine growth response resulting from the application of prescribed fire and herbicide, with and without fertilization. In southeast Texas, herbicide, prescribed fire and fertilizer treatments were applied in mid-rotational loblolly pine plantations 1.5 years after thinning. Five replications were established at each of two study sites...

  4. Substance abuse treatment response in a Latino sample: the influence of family conflict.

    PubMed

    Fish, Jessica N; Maier, Candice A; Priest, Jacob B

    2015-02-01

    Latino Americans report underutilization of treatment and poor treatment response for substance use and abuse compared to other racial/ethnic groups; thus, it is important to assess factors that contribute to these disparities. The current study objective was to assess the influence of family conflict on substance abuse treatment response in a sample of Latino Americans using two different yet complementary analyses. First, ordinary least squares regression was used to assess the association between overall family conflict and pre- and post-treatment substance use. Second, repeated measures latent class analysis was used to identify groups based on family member conflict and timing of conflict during treatment. Findings indicated that family conflict contributed unique variance to concurrent substance use; however pre-treatment family conflict was not related to post-treatment outcomes. Results also identified three distinct family conflict groups: no/low conflict, pre-treatment conflict, and post-treatment conflict who differed in pre- and post-treatment substance use. Post hoc investigation revealed that those who experienced pre-treatment conflict but low post-treatment conflict showed the greatest decrease in substance use. Findings highlight the importance of considering family conflict during all stages of treatment for Latino American substance users. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. Site-Specific Seismic Site Response Model for the Waste Treatment Plant, Hanford, Washington

    SciTech Connect

    Rohay, Alan C.; Reidel, Steve P.

    2005-02-24

    This interim report documents the collection of site-specific geologic and geophysical data characterizing the Waste Treatment Plant site and the modeling of the site-specific structure response to earthquake ground motions.

  6. Response to Stimulant Drug Treatment in Hyperactive Children: Prediction from EEG and Neurological Findings

    ERIC Educational Resources Information Center

    Satterfield, James H.; And Others

    1973-01-01

    A study of neurological examinations, electroencephalographic findings, and behavioral responses to methylphenidate treatment in 57 hyperactive boys, 5 to 10 years of age, is reported and discussed. (Author/MC)

  7. Do Processing Patterns of Strengths and Weaknesses Predict Differential Treatment Response?

    ERIC Educational Resources Information Center

    Miciak, Jeremy; Williams, Jacob L.; Taylor, W. Pat; Cirino, Paul T.; Fletcher, Jack M.; Vaughn, Sharon

    2016-01-01

    No previous empirical study has investigated whether the learning disabilities (LD) identification decisions of proposed methods to operationalize processing strengths and weaknesses approaches for LD identification are associated with differential treatment response. We investigated whether the identification decisions of the…

  8. Effects of treatment-integrity failures on a response-cost procedure.

    PubMed

    St Peter, Claire C; Byrd, Jeffrey D; Pence, Sacha T; Foreman, Apral P

    2016-06-01

    Effects of incorrect or partial implementation (poor treatment integrity) on response cost are largely unknown. We evaluated reduced treatment integrity during response cost on rates of 2 concurrently available responses. College students earned points by clicking on either a black circle or a red circle on a computer screen. Experiment 1 compared 2 types of treatment-integrity failures (omission and commission errors) across 2 levels of integrity (20% and 50%). Compared to 100% integrity conditions, omission errors did not suppress responding to the same extent, and commission errors reduced target responding but also decreased rates of alternative behavior. Experiment 2 compared the effects of 20% and 50% omission errors within subjects. Implementation at 50% integrity adequately suppressed responding, but treatment effects were lost at 20% integrity. There may be a critical level at which response cost must be implemented to suppress responding, which has important implications for application. © 2016 Society for the Experimental Analysis of Behavior.

  9. Do Processing Patterns of Strengths and Weaknesses Predict Differential Treatment Response?

    ERIC Educational Resources Information Center

    Miciak, Jeremy; Williams, Jacob L.; Taylor, W. Pat; Cirino, Paul T.; Fletcher, Jack M.; Vaughn, Sharon

    2016-01-01

    No previous empirical study has investigated whether the learning disabilities (LD) identification decisions of proposed methods to operationalize processing strengths and weaknesses approaches for LD identification are associated with differential treatment response. We investigated whether the identification decisions of the…

  10. Subjective response as a consideration in the pharmacogenetics of alcoholism treatment.

    PubMed

    Roche, Daniel Jo; Ray, Lara A

    2015-01-01

    Currently available pharmacological treatments for alcoholism have modest efficacy and high individual variability in treatment outcomes, both of which have been partially attributed to genetic factors. One path to reducing the variability and improving the efficacy associated with these pharmacotherapies may be to identify overlapping genetic contributions to individual differences in both subjective responses to alcohol and alcoholism pharmacotherapy outcomes. As acute subjective response to alcohol is highly predictive of future alcohol related problems, identifying such shared genetic mechanisms may inform the development of personalized treatments that can effectively target converging pathophysiological mechanisms that convey risk for alcoholism. The focus of this review is to revisit the association between subjective response to alcohol and the etiology of alcoholism while also describing genetic contributions to this relationship, discuss potential pharmacogenetic approaches to target subjective response to alcohol in order to improve the treatment of alcoholism and examine conceptual and methodological issues associated with these topics, and outline future approaches to overcome these challenges.

  11. Melancholic/endogenous depression and response to somatic treatment and placebo.

    PubMed

    Peselow, E D; Sanfilipo, M P; Difiglia, C; Fieve, R R

    1992-10-01

    The authors' goals were to examine the effects of somatic treatment and placebo in patients with and without endogenous/melancholic depression. Before entry into one of four trials of antidepressant drugs versus placebo, 231 patients were assessed as to whether they met Research Diagnostic Criteria for definite endogenous depression and/or DSM-III criteria for major depressive episode with melancholia. These patients were prospectively assessed for subsequent response to antidepressant treatment or placebo. Previous studies of the effect of endogenous/melancholic depression on treatment response were also reviewed. Of the 76 patients with DSM-III melancholia given active medication, 41 (54%) had a complete or partial response, but only 10 (23%) of the 44 patients with melancholia given placebo had a complete or partial response. Of the 76 depressed patients without melancholia given active medication, 46 (61%) had a complete or partial response, and 15 (43%) of the 35 depressed patients without melancholia given placebo had a complete or partial response. Moderately depressed patients with DSM-III melancholia had a significantly better response to active medication than did severely depressed patients with melancholia and showed the greatest difference between response to active medication and response to placebo. The results of the review of previous studies of the effect of endogenous/melancholic depression on treatment response were mixed. Depressed patients with melancholia were not particularly different from depressed patients without melancholia in their responses to antidepressant medication but did differ from patients without melancholia in their responses to active medication versus placebo, particularly if their depression was moderate and not severe. This suggests that patients with DSM-III melancholia may be unresponsive to nonsomatic treatments.

  12. MicroRNAs as putative mediators of treatment response in prostate cancer.

    PubMed

    O'Kelly, Fardod; Marignol, Laure; Meunier, Armelle; Lynch, Thomas H; Perry, Antoinette S; Hollywood, Donal

    2012-05-22

    MicroRNAs (miRNAs) are an abundant class of noncoding RNAs that function to regulate post-transcriptional gene expression, predominantly by translational repression. In addition to their role in prostate cancer initiation and progression, recent evidence suggests that miRNAs might also participate in treatment response across a range of therapies including radiation treatment, chemotherapy and androgen suppression. The mechanism of this regulation is thought to be multifactorial and is currently poorly understood. To date, only a small number of studies have examined the functional role of miRNAs in response to prostate cancer treatment. Elucidating the role of miRNAs in treatment response following radiotherapy, chemotherapy and androgen suppression will provide new avenues of investigation for the development of novel therapies for the treatment of prostate cancer.

  13. The role of p53 in treatment responses of lung cancer

    SciTech Connect

    Viktorsson, Kristina; Lewensohn, Rolf . E-mail: Rolf.Lewensohn@cck.ki.se

    2005-06-10

    Resistance to radio- and chemotherapy is a major problem in treatment responses of lung cancer. In this disease, biological markers, that can be predictive of response to treatment for guiding clinical practice, still need to be validated. Radiotherapy and most chemotherapeutic agents directly target DNA and in response to such therapies, p53 functions as a coordinator of the DNA repair process, cell cycle arrest, and apoptosis. In fact, it participates in the main DNA repair systems operative in cells, including NHEJ, HRR, NER, BER, and MMR. Given the high p53 mutation frequency in lung cancer which likely impairs some of the p53-mediated functions, a role of p53 as a predictive marker for treatment responses has been suggested. In this review, we summarize the conflicting results coming from preclinical and clinical studies on the role of p53 as a predictive marker of responses to chemotherapy or radiotherapy in lung cancer.

  14. Personality and treatment response in agoraphobia with panic attacks.

    PubMed

    Clair, A L; Oei, T P; Evans, L

    1992-01-01

    The present study investigated the association of specific personality characteristics with agoraphobia, and whether they predicted long-term outcome following a group cognitive behavior therapy program. Thirty-three patients with agoraphobia with panic attacks, 18 with social phobia, and 26 "normals" were used in the study. Personality factors were measured with the Maudsley Personality Inventory (MPI), the Hostility and Direction of Hostility Questionnaire (HDHQ), and the Fundamental Interpersonal Relations Orientation-Behavior Scale (FIRO-B). The results showed that (1) agoraphobics are more extroverted and more likely to include others in their activities than are social phobics; however, they are less extroverted, more neurotic, more hostile and intropunitive, and less likely to include others in their activities than are normals; (2) social phobics are similarly less extroverted, more neurotic, and more hostile and intropunitive than normals, but, in addition, are less likely to exert control over others, more likely to want to be controlled, and less expressive of affection than normals; and (3) personality characteristics did not predict treatment outcome.

  15. Diagnosis of response and non-response to dry eye treatment using infrared thermography images

    NASA Astrophysics Data System (ADS)

    Acharya, U. Rajendra; Tan, Jen Hong; Vidya, S.; Yeo, Sharon; Too, Cheah Loon; Lim, Wei Jie Eugene; Chua, Kuang Chua; Tong, Louis

    2014-11-01

    The dry eye treatment outcome depends on the assessment of clinical relevance of the treatment effect. The potential approach to assess the clinical relevance of the treatment is to identify the symptoms responders and non-responders to the given treatments using the responder analysis. In our work, we have performed the responder analysis to assess the clinical relevance effect of the dry eye treatments namely, hot towel, EyeGiene®, and Blephasteam® twice daily and 12 min session of Lipiflow®. Thermography is performed at week 0 (baseline), at weeks 4 and 12 after treatment. The clinical parameters such as, change in the clinical irritations scores, tear break up time (TBUT), corneal staining and Schirmer's symptoms tests values are used to obtain the responders and non-responders groups. We have obtained the infrared thermography images of dry eye symptoms responders and non-responders to the three types of warming treatments. The energy, kurtosis, skewness, mean, standard deviation, and various entropies namely Shannon, Renyi and Kapoor are extracted from responders and non-responders thermograms. The extracted features are ranked based on t-values. These ranked features are fed to the various classifiers to get the highest performance using minimum features. We have used decision tree (DT), K nearest neighbour (KNN), Naves Bayesian (NB) and support vector machine (SVM) to classify the features into responder and non-responder classes. We have obtained an average accuracy of 99.88%, sensitivity of 99.7% and specificity of 100% using KNN classifier using ten-fold cross validation.

  16. Identifying sub-optimal responses to ivermectin in the treatment of River Blindness

    PubMed Central

    Churcher, Thomas S.; Pion, Sébastien D. S.; Osei-Atweneboana, Mike Y.; Prichard, Roger K.; Awadzi, Kwablah; Boussinesq, Michel; Collins, Richard C.; Whitworth, James A.; Basáñez, María-Gloria

    2009-01-01

    Identification of drug resistance before it becomes a public health concern requires a clear distinction between what constitutes a normal and a suboptimal treatment response. A novel method of analyzing drug efficacy studies in human helminthiases is proposed and used to investigate recent claims of atypical responses to ivermectin in the treatment of River Blindness. The variability in the rate at which Onchocerca volvulus microfilariae repopulate host's skin following ivermectin treatment is quantified using an individual-based onchocerciasis mathematical model. The model estimates a single skin repopulation rate for every host sampled, allowing reports of suboptimal responses to be statistically compared with responses from populations with no prior exposure to ivermectin. Statistically faster rates of skin repopulation were observed in 3 Ghanaian villages (treated 12–17 times), despite the wide variability in repopulation rates observed in ivermectin-naïve populations. Another village previously thought to have high rates of skin repopulation was shown to be indistinguishable from the normal treatment response. The model is used to generate testable hypotheses to identify whether atypical rates of skin repopulation by microfilariae could result from low treatment coverage alone or provide evidence of decreased ivermectin efficacy. Further work linking phenotypic poor responses to treatment with parasite molecular genetics markers will be required to confirm drug resistance. Limitations of the skin-snipping method for estimating parasite load indicates that changes in the distribution of microfilarial repopulation rates, rather than their absolute values, maybe a more sensitive indicator of emerging ivermectin resistance. PMID:19805362

  17. Identifying sub-optimal responses to ivermectin in the treatment of River Blindness.

    PubMed

    Churcher, Thomas S; Pion, Sébastien D S; Osei-Atweneboana, Mike Y; Prichard, Roger K; Awadzi, Kwablah; Boussinesq, Michel; Collins, Richard C; Whitworth, James A; Basáñez, María-Gloria

    2009-09-29

    Identification of drug resistance before it becomes a public health concern requires a clear distinction between what constitutes a normal and a suboptimal treatment response. A novel method of analyzing drug efficacy studies in human helminthiases is proposed and used to investigate recent claims of atypical responses to ivermectin in the treatment of River Blindness. The variability in the rate at which Onchocerca volvulus microfilariae repopulate host's skin following ivermectin treatment is quantified using an individual-based onchocerciasis mathematical model. The model estimates a single skin repopulation rate for every host sampled, allowing reports of suboptimal responses to be statistically compared with responses from populations with no prior exposure to ivermectin. Statistically faster rates of skin repopulation were observed in 3 Ghanaian villages (treated 12-17 times), despite the wide variability in repopulation rates observed in ivermectin-naïve populations. Another village previously thought to have high rates of skin repopulation was shown to be indistinguishable from the normal treatment response. The model is used to generate testable hypotheses to identify whether atypical rates of skin repopulation by microfilariae could result from low treatment coverage alone or provide evidence of decreased ivermectin efficacy. Further work linking phenotypic poor responses to treatment with parasite molecular genetics markers will be required to confirm drug resistance. Limitations of the skin-snipping method for estimating parasite load indicates that changes in the distribution of microfilarial repopulation rates, rather than their absolute values, maybe a more sensitive indicator of emerging ivermectin resistance.

  18. Dysphonia in preterm children: assessing incidence and response to treatment.

    PubMed

    Reynolds, Victoria; Meldrum, Suzanne; Simmer, Karen; Vijayasekaran, Shyan; French, Noel P

    2014-03-01

    Mild dysphonia in childhood is surprisingly common, yet moderate to severe dysphonia is rare. The latter has been associated with complex medical conditions and congenital abnormalities. Intubation injury has also been documented as a cause of childhood dysphonia. Children born very preterm may be intubated as part of the intensive care administered in the perinatal and neonatal periods, yet there are few studies investigating dysphonia in this population. This study will be the first to: use an objective acoustic voice assessment in a paediatric study, document the incidence of dysphonia in very preterm children at school age, and conduct a controlled trial of behavioural voice therapy in this population. This study will consist of three phases: assessment of voice quality and its impact on quality of life in up to 200 children born at less than 32 weeks' gestation: assessment of the nature and extent of laryngeal pathology in children with moderate to severe dysphonia; and a non-blinded, randomised controlled trial of behavioural voice therapy in children with moderate to severe dysphonia. This study will be the first to use clinical assessment to examine the voice quality of very preterm children, and to use fibre optic endoscopic evaluation of laryngeal function to determine the nature and extent of any laryngeal pathology in such children. Those participants with significant voice difficulties will be randomised to receive treatment immediately or after the eight week assessment. This study is registered on the Australian New Zealand Clinical Trials Registry (ACTRN12613001015730/ACTRN12613001012763). Crown Copyright © 2013. Published by Elsevier Inc. All rights reserved.

  19. Using biomarkers to predict treatment response in major depressive disorder: evidence from past and present studies.

    PubMed

    Thase, Michael E

    2014-12-01

    Major depressive disorder (MDD) is a heterogeneous condition with a variable response to a wide range of treatments. Despite intensive efforts, no biomarker has been identified to date that can reliably predict response or non-response to any form of treatment, nor has one been identified that can be used to identify those at high risk of developing treatment-resistant depression (ie, non-response to a sequence of treatments delivered for adequate duration and intensity). This manuscript reviews some past areas of research that have proved informative, such as studies using indexes of hypercortisolism or sleep disturbance, and more recent research findings using measures of inflammation and different indicators of regional cortical activation to predict treatment response. It is concluded that, although no method has yet been demonstrated to be sufficiently accurate to be applied in clinical practice, progress has been made. It thus seems likely that--at some point in the not-too-distant future--it will be possible to prospectively identify, at least for some MDD patients, the likelihood of response or non-response to cognitive therapy or various antidepressant medications.

  20. Evaluating and monitoring treatment response in depression using measurement-based assessment and rating scales.

    PubMed

    Trivedi, Madhukar H

    2013-07-01

    Even with many treatment options available for major depressive disorder, many patients fail to achieve remission and return to their presymptomatic levels of functioning at work, in leisure activities, and in relationships. Throughout treatment, clinicians should implement measurement-based care by systematically monitoring patients' response using self-rated scales, such as the PHQ-9, QIDS-SR, or BDI. By tracking depressive symptoms, as well as suicidality, treatment adherence, and side effects, clinicians can adjust treatment to help patients achieve the best outcomes. Measurement-based care enables clinicians to make informed decisions at critical points throughout the treatment process and to involve patients in making those decisions.

  1. Impact of Physical and Sexual Abuse on Treatment Response in the Treatment of Resistant Depression in Adolescent Study (TORDIA)

    PubMed Central

    Shamseddeen, Wael; Asarnow, Joan Rosenbaum; Clarke, Gregory; Vitiello, Benedetto; Wagner, Karen Dineen; Birmaher, Boris; Keller, Martin B.; Emslie, Graham; Iyengar, Satish; Ryan, Neal D.; McCracken, James T.; Porta, Giovanna; Mayes, Taryn; Brent, David A.

    2010-01-01

    Objective We previously reported that a history of abuse was associated with a poorer response to combination treatment in the Treatment of Resistant Depression in Adolescents study (TORDIA). We now report on the nature and correlates of abuse that might explain these findings. Method Youth who did not benefit from an adequate selective serotonin re-uptake inhibitor (SSRI) trial (N=334) were randomized to: an alternative SSRI; an alternative SSRI plus cognitive behavior therapy (CBT); venlafaxine; or venlafaxine plus CBT. Analyses examined the effect of history of abuse on response to the pharmacotherapy and combination therapy. Results Those without a history of physical abuse (PA) or sexual abuse (SA) had a higher 12-week response rate to combination therapy compared to medication mono-therapy (62.8% vs. 37.6%; OR=2.8, 95% CI: 1.6–4.7, p<0.001). Those with a history of SA had similar response rates to combination vs. medication monotherapy (48.3% vs. 42.3%; OR=1.3, 95% CI: 0.4–3.7; p=0.66), while those with history of PA had a much lower rate of response to combination therapy (18.4% vs. 52.4%, OR=0.1; 95% CI: 0.02–0.43). Even after adjusting for other clinical predictors, a history of PA moderated treatment outcome. Conclusion These results should be considered within the limitations of a post-hoc analysis, lack of detailed assessment of abuse and other forms of trauma, and neuropsychological status. Depressed patients with history of abuse, especially PA may require specialized clinical approaches. Further work is needed to understand by what mechanisms a history of abuse affects treatment response. PMID:21334569

  2. Validation of functional imaging as a biomarker for radiation treatment response.

    PubMed

    Jentsch, C; Beuthien-Baumann, B; Troost, E G C; Shakirin, G

    2015-07-01

    Major advances in radiotherapy techniques, increasing knowledge of tumour biology and the ability to translate these advances into new therapeutic approaches are important goals towards more individualized cancer treatment. With the development of non-invasive functional and molecular imaging techniques such as positron emission tomography (PET)-CT scanning and MRI, there is now a need to evaluate potential new biomarkers for tumour response prediction, for treatment individualization is not only based on morphological criteria but also on biological tumour characteristics. The goal of individualization of radiotherapy is to improve treatment outcome and potentially reduce chronic treatment toxicity. This review gives an overview of the molecular and functional imaging modalities of tumour hypoxia and tumour cell metabolism, proliferation and perfusion as predictive biomarkers for radiation treatment response in head and neck tumours and in lung tumours. The current status of knowledge on integration of PET/CT/MRI into treatment management and bioimage-guided adaptive radiotherapy are discussed.

  3. Inmate responses to prison-based drug treatment: a repeated measures analysis.

    PubMed

    Welsh, Wayne N

    2010-06-01

    Using a sample of 347 prison inmates and general linear modeling (GLM) repeated measures analyses, this paper examined during-treatment responses (e.g., changes in psychological and social functioning) to prison-based TC drug treatment. These effects have rarely been examined in previous studies, and never with a fully multivariate model accounting for within-subjects effects (changes over time), between-subjects effects (e.g., levels of risk and motivation), and within/between-subjects interactions (timexriskxmotivation). The results provide evidence of positive inmate change in response to prison TC treatment, but the patterns of results varied depending upon: (a) specific indicators of psychological and social functioning, motivation, and treatment process; (b) the time periods examined (1, 6, and 12 months during treatment); and (c) baseline levels of risk and motivation. Significant interactions between time and type of inmate suggest important new directions for research, theory, and practice in offender-based substance abuse treatment.

  4. Brief Report: Reduced Restricted and Repetitive Behaviors after Pivotal Response Treatment

    ERIC Educational Resources Information Center

    Ventola, Pamela E.; Yang, Daniel; Abdullahi, Sebiha M.; Paisley, Courtney A.; Braconnier, Megan L.; Sukhodolsky, Denis G.

    2016-01-01

    Children with ASD show high frequency of restricted and repetitive behaviors (RRBs); however, higher-order RRBs, such as restricted interests, have remained largely resistant to treatment. This study evaluated change in severity of RRBs following a 16-weeks open trial of Pivotal Response Treatment (PRT). Participants included 15 children with ASD…

  5. Effectiveness of Community-Based Early Intervention Based on Pivotal Response Treatment

    ERIC Educational Resources Information Center

    Smith, Isabel M.; Flanagan, Helen E.; Garon, Nancy; Bryson, Susan E.

    2015-01-01

    Preschoolers (n = 118) with autism spectrum disorder (ASD) participated in this prospective effectiveness study of an early intervention program. Treatment entailed parent training and therapist-implemented components, incorporating Pivotal Response Treatment and Positive Behaviour Support. Standardized ability and behavioural measures were…

  6. Thermal treatment for increasing magnetostrictive response of rare earth-iron alloy rods

    DOEpatents

    Verhoeven, John D.; McMasters, O. D.

    1989-07-18

    Magnetostrictive rods formed from rare earth-iron alloys are subjected to a short time heat treatment to increase their Magnetostrictive response under compression. The heat treatment is preferably carried out at a temperature of from 900.degree. to 1000.degree. C. for 20 minutes to six hours.

  7. Thermal treatment for increasing magnetostrictive response of rare earth-iron alloy rods

    DOEpatents

    Verhoeven, J.D.; McMasters, O.D.

    1989-07-18

    Magnetostrictive rods formed from rare earth-iron alloys are subjected to a short time heat treatment to increase their magnetostrictive response under compression. The heat treatment is preferably carried out at a temperature of from 900 to 1,000 C for 20 minutes to six hours.

  8. The PRT Pocket Guide: Pivotal Response Treatment for Autism Spectrum Disorders

    ERIC Educational Resources Information Center

    Koegel, Robert L.; Koegel, Lynn Kern

    2012-01-01

    What is Pivotal Response Treatment? What's the research behind it, what does it look like in practice, and what are some good examples of how to use it? Now one concise book gives professionals and parents all the basics of the widely used PRT--one of a select group of highly effective, evidence-based treatments for autism. great resource for…

  9. Large Scale Dissemination and Community Implementation of Pivotal Response Treatment: Program Description and Preliminary Data

    ERIC Educational Resources Information Center

    Bryson, Susan E.; Koegel, Lynn K.; Koegel, Robert L.; Openden, Daniel; Smith, Isabel M.; Nefdt, Nicolette

    2007-01-01

    This paper describes a collaborative effort aimed at province-wide dissemination and implementation of pivotal response treatment (PRT) for young children with autism spectrum disorder (ASD) in Nova Scotia, Canada. Three critical components of the associated training model are described: (1) direct training of treatment teams (parents, one-to-one…

  10. Predicting Response of ADHD Symptoms to Methylphenidate Treatment Based on Comorbid Anxiety

    ERIC Educational Resources Information Center

    Blouin, Brittany; Maddeaux, Cindy; Stanley Firestone, Jill; van Stralen, Judy

    2010-01-01

    Objective: In this small pilot study, the association of comorbid anxiety with the treatment of ADHD is studied. Methods: Eighteen volunteers from a pediatric clinic are tested for ADHD and anxiety and assessed for behavioral and cognitive ADHD symptomology. Response to methylphenidate as treatment for ADHD symptoms is measured 2 to 3 weeks, and…

  11. Quick response small catchment monitoring techniques for comparing postfire rehabilitation treatment effectiveness

    Treesearch

    Peter R. Robichaud; Robert E. Brown

    2003-01-01

    Increased runoff and erosion commonly occur after wildfires with the onset of precipitation events. Various erosion mitigation treatments are often used after wildfires to reduce flooding and sedimentation. The effectiveness of these treatments has not been well documented in the literature; therefore we undertook a rapid response approach (within four weeks following...

  12. The PRT Pocket Guide: Pivotal Response Treatment for Autism Spectrum Disorders

    ERIC Educational Resources Information Center

    Koegel, Robert L.; Koegel, Lynn Kern

    2012-01-01

    What is Pivotal Response Treatment? What's the research behind it, what does it look like in practice, and what are some good examples of how to use it? Now one concise book gives professionals and parents all the basics of the widely used PRT--one of a select group of highly effective, evidence-based treatments for autism. great resource for…

  13. Childhood Maltreatment and Differential Treatment Response and Recurrence in Adult Major Depressive Disorder

    ERIC Educational Resources Information Center

    Harkness, Kate L.; Bagby, R. Michael; Kennedy, Sidney H.

    2012-01-01

    Objective: A substantial number of patients with major depressive disorder (MDD) do not respond to treatment, and recurrence rates remain high. The purpose of this study was to examine a history of severe childhood abuse as a moderator of response following a 16-week acute treatment trial, and of recurrence over a 12-month follow-up. Method:…

  14. Predicting Response of ADHD Symptoms to Methylphenidate Treatment Based on Comorbid Anxiety

    ERIC Educational Resources Information Center

    Blouin, Brittany; Maddeaux, Cindy; Stanley Firestone, Jill; van Stralen, Judy

    2010-01-01

    Objective: In this small pilot study, the association of comorbid anxiety with the treatment of ADHD is studied. Methods: Eighteen volunteers from a pediatric clinic are tested for ADHD and anxiety and assessed for behavioral and cognitive ADHD symptomology. Response to methylphenidate as treatment for ADHD symptoms is measured 2 to 3 weeks, and…

  15. Treatment Response in CP/ADHD Children with Callous/Unemotional Traits

    ERIC Educational Resources Information Center

    Haas, Sarah M.; Waschbusch, Daniel A.; Pelham, William E.; King, Sara; Andrade, Brendan F.; Carrey, Normand J.

    2011-01-01

    The current study examines the role of callous/unemotional (CU) traits in response to treatment among children with conduct problems (CP) and attention-deficit/hyperactivity disorder (ADHD). Fifty-four children with CP/ADHD and 16 controls (age = 9.48, SD = 1.58) took part in a summer treatment and research program. Simple correlations showed that…

  16. Examining Heterogeneity in Residual Variance to Detect Differential Response to Treatments

    ERIC Educational Resources Information Center

    Kim, Jinok; Seltzer, Michael

    2011-01-01

    Individual differences in response to treatments have been a long-standing interest in education, psychology, and related fields. This article presents a conceptual framework and hierarchical modeling strategies that may help identify the subgroups for whom, or the conditions under which, a particular treatment is associated with better outcomes.…

  17. Examining Heterogeneity in Residual Variance to Detect Differential Response to Treatments

    ERIC Educational Resources Information Center

    Kim, Jinok; Seltzer, Michael

    2011-01-01

    Individual differences in response to treatments have been a long-standing interest in education, psychology, and related fields. This article presents a conceptual framework and hierarchical modeling strategies that may help identify the subgroups for whom, or the conditions under which, a particular treatment is associated with better outcomes.…

  18. Treatment Response in CP/ADHD Children with Callous/Unemotional Traits

    ERIC Educational Resources Information Center

    Haas, Sarah M.; Waschbusch, Daniel A.; Pelham, William E.; King, Sara; Andrade, Brendan F.; Carrey, Normand J.

    2011-01-01

    The current study examines the role of callous/unemotional (CU) traits in response to treatment among children with conduct problems (CP) and attention-deficit/hyperactivity disorder (ADHD). Fifty-four children with CP/ADHD and 16 controls (age = 9.48, SD = 1.58) took part in a summer treatment and research program. Simple correlations showed that…

  19. Childhood Maltreatment and Differential Treatment Response and Recurrence in Adult Major Depressive Disorder

    ERIC Educational Resources Information Center

    Harkness, Kate L.; Bagby, R. Michael; Kennedy, Sidney H.

    2012-01-01

    Objective: A substantial number of patients with major depressive disorder (MDD) do not respond to treatment, and recurrence rates remain high. The purpose of this study was to examine a history of severe childhood abuse as a moderator of response following a 16-week acute treatment trial, and of recurrence over a 12-month follow-up. Method:…

  20. Empirically and Clinically Useful Decision Making in Psychotherapy: Differential Predictions with Treatment Response Models

    ERIC Educational Resources Information Center

    Lutz, Wolfgang; Saunders, Stephen M.; Leon, Scott C.; Martinovich, Zoran; Kosfelder, Joachim; Schulte, Dietmar; Grawe, Klaus; Tholen, Sven

    2006-01-01

    In the delivery of clinical services, outcomes monitoring (i.e., repeated assessments of a patient's response to treatment) can be used to support clinical decision making (i.e., recurrent revisions of outcome expectations on the basis of that response). Outcomes monitoring can be particularly useful in the context of established practice research…

  1. Response of conifer-encroached shrublands in the Great Basin to prescribed fire and mechanical treatments

    Treesearch

    Richard F. Miller; Jaime Ratchford; Bruce A. Roundy; Robin J. Tausch; April Hulet; Jeanne Chambers

    2014-01-01

    In response to the recent expansion of pinon and juniper woodlands into sagebrush-steppe communities in the northern Great Basin region, numerous conifer-removal projects have been implemented, primarily to release understory vegetation at sites having a wide range of environmental conditions. Responses to these treatments have varied from successful restoration of...

  2. Empirically and Clinically Useful Decision Making in Psychotherapy: Differential Predictions with Treatment Response Models

    ERIC Educational Resources Information Center

    Lutz, Wolfgang; Saunders, Stephen M.; Leon, Scott C.; Martinovich, Zoran; Kosfelder, Joachim; Schulte, Dietmar; Grawe, Klaus; Tholen, Sven

    2006-01-01

    In the delivery of clinical services, outcomes monitoring (i.e., repeated assessments of a patient's response to treatment) can be used to support clinical decision making (i.e., recurrent revisions of outcome expectations on the basis of that response). Outcomes monitoring can be particularly useful in the context of established practice research…

  3. Differential responses of Bolivian timber species to prescribed fire and other gap treatments

    Treesearch

    Debora K. Kennard; Francis E. Putz

    2005-01-01

    We followed the establishment and growth response of 13 commercial tree species to canopy opening, above-ground biomass removal, and experimental burns of low and high intensities in a lowland dry forest in Bolivia. Three patterns of response to treatments were observed among the most abundant commercial tree species. (1) Shade-intolerant species regenerated mostly...

  4. Prediction of Response to Medication and Cognitive Therapy in the Treatment of Moderate to Severe Depression

    ERIC Educational Resources Information Center

    Fournier, Jay C.; DeRubeis, Robert J.; Shelton, Richard C.; Hollon, Steven D.; Amsterdam, Jay D.; Gallop, Robert

    2009-01-01

    A recent randomized controlled trial found nearly equivalent response rates for antidepressant medications and cognitive therapy in a sample of moderate to severely depressed outpatients. In this article, the authors seek to identify the variables that were associated with response across both treatments as well as variables that predicted…

  5. Prediction of Response to Medication and Cognitive Therapy in the Treatment of Moderate to Severe Depression

    ERIC Educational Resources Information Center

    Fournier, Jay C.; DeRubeis, Robert J.; Shelton, Richard C.; Hollon, Steven D.; Amsterdam, Jay D.; Gallop, Robert

    2009-01-01

    A recent randomized controlled trial found nearly equivalent response rates for antidepressant medications and cognitive therapy in a sample of moderate to severely depressed outpatients. In this article, the authors seek to identify the variables that were associated with response across both treatments as well as variables that predicted…

  6. Residential treatment for combat-related posttraumatic stress disorder: identifying trajectories of change and predictors of treatment response.

    PubMed

    Currier, Joseph M; Holland, Jason M; Drescher, Kent D

    2014-01-01

    Combat-related posttraumatic stress disorder (PTSD) can be a difficult condition to treat and has been associated with serious medical and economic issues among U.S. military veterans. Distinguishing between treatment responders vs. non-responders in this population has become an important public health priority. This study was conducted to identify pre-treatment characteristics of U.S. veterans with combat-related PTSD that might contribute to favorable and unfavorable responses to high value treatments for this condition. This study focused on 805 patients who completed a VHA PTSD residential program between 2000 and 2007. These patients completed the PTSD Clinical Checklist at pre-treatment, post-treatment, and a four-month follow-up assessment. Latent growth curve analysis (LCGA) was incorporated to determine trajectories of changes in PTSD across these assessments and whether several key clinical concerns for this population were associated with their treatment responses. LCGA indicated three distinct trajectories in PTSD outcomes and identified several clinical factors that were prospectively linked with changes in veterans' posttraumatic symptomatology. When compared to a group with high PTSD symptom severity that decreased over the program but relapsed at follow-up (41%), the near half (48.8%) of the sample with an improving trajectory had less combat exposure and superior physical/mental health. However, when compared to a minority (10.2%) with relatively low symptomatology that also remained somewhat stable, patients in the improving group were younger and also reported greater combat exposure, poorer physical/mental health status, and more problems with substance abuse before the start of treatment. Findings suggest that veterans are most likely to benefit from residential treatment in an intermediate range of symptoms and risk factors, including PTSD symptom severity, history of combat exposure, and comorbid issues with physical/mental health

  7. A functional magnetic resonance imaging predictor of treatment response to venlafaxine in generalized anxiety disorder.

    PubMed

    Whalen, Paul J; Johnstone, Tom; Somerville, Leah H; Nitschke, Jack B; Polis, Sara; Alexander, Andrew L; Davidson, Richard J; Kalin, Ned H

    2008-05-01

    Functional magnetic resonance imaging (fMRI) holds promise as a noninvasive means of identifying neural responses that can be used to predict treatment response before beginning a drug trial. Imaging paradigms employing facial expressions as presented stimuli have been shown to activate the amygdala and anterior cingulate cortex (ACC). Here, we sought to determine whether pretreatment amygdala and rostral ACC (rACC) reactivity to facial expressions could predict treatment outcomes in patients with generalized anxiety disorder (GAD). Fifteen subjects (12 female subjects) with GAD participated in an open-label venlafaxine treatment trial. Functional magnetic resonance imaging responses to facial expressions of emotion collected before subjects began treatment were compared with changes in anxiety following 8 weeks of venlafaxine administration. In addition, the magnitude of fMRI responses of subjects with GAD were compared with that of 15 control subjects (12 female subjects) who did not have GAD and did not receive venlafaxine treatment. The magnitude of treatment response was predicted by greater pretreatment reactivity to fearful faces in rACC and lesser reactivity in the amygdala. These individual differences in pretreatment rACC and amygdala reactivity within the GAD group were observed despite the fact that 1) the overall magnitude of pretreatment rACC and amygdala reactivity did not differ between subjects with GAD and control subjects and 2) there was no main effect of treatment on rACC-amygdala reactivity in the GAD group. These findings show that this pattern of rACC-amygdala responsivity could prove useful as a predictor of venlafaxine treatment response in patients with GAD.

  8. A Functional Magnetic Resonance Imaging Predictor of Treatment Response to Venlafaxine in Generalized Anxiety Disorder

    PubMed Central

    Johnstone, Tom; Somerville, Leah H.; Nitschke, Jack B.; Polis, Sara; Alexander, Andrew L.; Davidson, Richard J.; Kalin, Ned H.

    2008-01-01

    Background Functional magnetic resonance imaging (fMRI) holds promise as a noninvasive means of identifying neural responses that can be used to predict treatment response before beginning a drug trial. Imaging paradigms employing facial expressions as presented stimuli have been shown to activate the amygdala and anterior cingulate cortex (ACC). Here, we sought to determine whether pretreatment amygdala and rostral ACC (rACC) reactivity to facial expressions could predict treatment outcomes in patients with generalized anxiety disorder (GAD). Methods Fifteen subjects (12 female subjects) with GAD participated in an open-label venlafaxine treatment trial. Functional magnetic resonance imaging responses to facial expressions of emotion collected before subjects began treatment were compared with changes in anxiety following 8 weeks of venlafaxine administration. In addition, the magnitude of fMRI responses of subjects with GAD were compared with that of 15 control subjects (12 female subjects) who did not have GAD and did not receive venlafaxine treatment. Results The magnitude of treatment response was predicted by greater pretreatment reactivity to fearful faces in rACC and lesser reactivity in the amygdala. These individual differences in pretreatment rACC and amygdala reactivity within the GAD group were observed despite the fact that 1) the overall magnitude of pretreatment rACC and amygdala reactivity did not differ between subjects with GAD and control subjects and 2) there was no main effect of treatment on rACC-amygdala reactivity in the GAD group. Conclusions These findings show that this pattern of rACC-amygdala responsivity could prove useful as a predictor of venlafaxine treatment response in patients with GAD. PMID:17964548

  9. Factors Influencing Response to Pharmacologic Treatment of Migraine in a Pediatric Headache Clinic.

    PubMed

    Markus, Tal Eidlitz; Moad, Bder; Haimi-Cohen, Yishai; Zeharia, Avraham

    2016-07-01

    The responses of different patients to the same drug may vary as a consequence of biologic, psychosocial, and genetic differences. The aim of this study was to identify clinical factors associated with a response to pharmacologic treatment in pediatric patients with migraine. The medical files of patients with migraine attending the headache clinic of a tertiary pediatric medical center in 2010-2015 were reviewed. The children and parents (or only the parents if the child was very young) completed the International Headache Society-based questionnaire. Patients were treated with at least one of the following medications: propranolol, amitriptyline, topiramate. Response to treatment was rated as no change in migraine pattern (grade 1) or a decrease in migraine attack frequency per month by at least 50% (grade 2) or at least 75% (grade 3). The highest-grade response to any pharmacologic treatment was defined as the best clinical response. The study group included 248 patients of mean age 12.71 ± 3.04 years. A grade 3 best clinical response was significantly associated with a positive maternal history of migraine, younger age at treatment onset, lower frequency of headache attacks per month, postpubertal children had a significantly lower rate of grade 3 response than prepubertal children (P < .05). Analysis of the association of overuse of medication and treatment response achieved a P value equal to .05. Several background and clinical factors are identified that may predispose children with migraine to respond better to pharmacologic treatment. Clinicians who see children with migraine in a pediatric headache clinic setting should consider these factors before initiating a treatment program. © 2016 American Headache Society.

  10. Multidimensional prediction of treatment response to antidepressants with cognitive control and functional MRI.

    PubMed

    Crane, Natania A; Jenkins, Lisanne M; Bhaumik, Runa; Dion, Catherine; Gowins, Jennifer R; Mickey, Brian J; Zubieta, Jon-Kar; Langenecker, Scott A

    2017-02-01

    Predicting treatment response for major depressive disorder can provide a tremendous benefit for our overstretched health care system by reducing number of treatments and time to remission, thereby decreasing morbidity. The present study used neural and performance predictors during a cognitive control task to predict treatment response (% change in Hamilton Depression Rating Scale pre- to post-treatment). Forty-nine individuals diagnosed with major depressive disorder were enrolled with intent to treat in the open-label study; 36 completed treatment, had useable data, and were included in most data analyses. Participants included in the data analysis sample received treatment with escitalopram (n = 22) or duloxetine (n = 14) for 10 weeks. Functional MRI and performance during a Parametric Go/No-go test were used to predict per cent reduction in Hamilton Depression Rating Scale scores after treatment. Haemodynamic response function-based contrasts and task-related independent components analysis (subset of sample: n = 29) were predictors. Independent components analysis component beta weights and haemodynamic response function modelling activation during Commission errors in the rostral and dorsal anterior cingulate, mid-cingulate, dorsomedial prefrontal cortex, and lateral orbital frontal cortex predicted treatment response. In addition, more commission errors on the task predicted better treatment response. Together in a regression model, independent component analysis, haemodynamic response function-modelled, and performance measures predicted treatment response with 90% accuracy (compared to 74% accuracy with clinical features alone), with 84% accuracy in 5-fold, leave-one-out cross-validation. Convergence between performance markers and functional magnetic resonance imaging, including novel independent component analysis techniques, achieved high accuracy in prediction of treatment response for major depressive disorder. The strong link to a task paradigm

  11. Time-dependent micromechanical responses of breast cancer cells and adjacent fibroblasts to electric treatment.

    PubMed

    Yizraeli, Maayan Lia; Weihs, Daphne

    2011-12-01

    Direct-current, low-intensity, electric fields were suggested as a minimally invasive treatment for various cancers. The tumor microenvironment may affect treatment efficacy, albeit it has not generally been considered when evaluating novel anti-cancer treatments. We evaluate the effects of electric treatment on epithelial, breast-cancer cells, co-cultured with non-cancerous fibroblasts, a simplified model for the tumor-microenvironment. We evaluate changes in morphology, cytoskeleton, and focus on dynamic intracellular structure and mechanics. Multiple-particle tracking was used within living cells to quantify time-dependent structural and mechanical changes. Cancer cells suffer severe cell death and exhibit transient rounding and changes in internal structural and mechanics. Interestingly, treating cancer cells in co-culture with fibroblasts delays and reduces their responses to treatment. Our particle-tracking data indicates a mechanism relating the observed changes in intracellular transport to transient changes in the microtubule network and its motors. In contrast, fibroblasts are only minimally affected by treatment, separately or in co-culture. To conclude, intracellular mechanics reveal time-dependent responses after treatment, unavailable by bulk measurements. This time-dependence could provide a window of opportunity for continued treatment. We demonstrate the importance of evaluating anti-cancer treatments within their microenvironment, which can affect response magnitude and time-course.

  12. Placebo response in the treatment of women's sexual dysfunctions: a review and commentary.

    PubMed

    Bradford, Andrea; Meston, Cindy M

    2009-01-01

    We reviewed the literature to determine the nature and magnitude of therapeutic response associated with placebo treatment in clinical trials for women's sexual dysfunction. We abstracted data from 16 articles to record the effect size associated with placebo treatment. In most of these studies, placebo recipients reported statistically significant improvements on one or more major endpoints relative to baseline. Although placebo responses varied across study populations and methodologies, within-group effect sizes were predominantly in the moderate range. Our findings suggest that post-menopausal women and women with hypoactive sexual desire disorder may be more likely to respond to placebo treatment.

  13. Prognostic factors versus markers of response to treatment versus surrogate endpoints: Three different concepts.

    PubMed

    Sormani, Maria Pia

    2017-03-01

    Multiple sclerosis is a highly heterogeneous disease; the quantitative assessment of disease progression is problematic for many reasons, including the lack of objective methods to measure disability and the long follow-up times needed to detect relevant and stable changes. For these reasons, the importance of prognostic markers, markers of response to treatments and of surrogate endpoints, is crucial in multiple sclerosis research. Aim of this report is to clarify some basic definitions and methodological issues about baseline factors to be considered prognostic markers or markers of response to treatment; to define the dynamic role that variables must have to be considered surrogate markers in relation to specific treatments.

  14. ¹⁸F-FDG PET/CT for Monitoring of Treatment Response in Breast Cancer.

    PubMed

    Avril, Stefanie; Muzic, Raymond F; Plecha, Donna; Traughber, Bryan J; Vinayak, Shaveta; Avril, Norbert

    2016-02-01

    Changes in tumor metabolic activity have been shown to be an early indicator of treatment effectiveness for breast cancer, mainly in the neoadjuvant setting. The histopathologic response at the completion of chemotherapy has been used as the reference standard for assessment of the accuracy of (18)F-FDG PET in predicting a response during systemic treatment. Although a pathologic complete response (pCR) remains an important positive prognostic factor for an individual patient, a recent metaanalysis could validate pCR as a surrogate marker for patient outcomes only in aggressive breast cancer subtypes. For establishment of the clinical application of metabolic treatment response studies, larger series of specific breast cancer subtypes-including hormone receptor-positive, human epidermal growth factor receptor 2-positive, and triple-negative breast cancers-are necessary. In addition, thresholds for relative changes in (18)F-FDG uptake to distinguish between responding and nonresponding tumors need to be validated for different systemic treatment approaches, with progression-free survival and overall survival as references. A PET-based treatment stratification is applicable clinically only if valid alternative therapies are available. Of note, patients who do not achieve a pCR might still benefit from neoadjuvant therapy enabling breast-conserving surgery. In the metastatic setting, residual tumor metabolic activity after the initiation of systemic therapy is an indicator of active disease, whereas a complete resolution of metabolic activity is predictive of a successful treatment response.

  15. 18F-FDG PET/CT for Monitoring of Treatment Response in Breast Cancer

    PubMed Central

    Avril, Stefanie; Muzic, Raymond F.; Plecha, Donna; Traughber, Bryan J.; Vinayak, Shaveta; Avril, Norbert

    2016-01-01

    Changes in tumor metabolic activity have been shown to be an early indicator of treatment effectiveness for breast cancer, mainly in the neoadjuvant setting. The histopathologic response at the completion of chemotherapy has been used as the reference standard for assessment of the accuracy of 18F-FDG PET in predicting a response during systemic treatment. Although a pathologic complete response (pCR) remains an important positive prognostic factor for an individual patient, a recent metaanalysis could validate pCR as a surrogate marker for patient outcomes only in aggressive breast cancer subtypes. For establishment of the clinical application of metabolic treatment response studies, larger series of specific breast cancer subtypes—including hormone receptor–positive, human epidermal growth factor receptor 2–positive, and triple-negative breast cancers—are necessary. In addition, thresholds for relative changes in 18F-FDG uptake to distinguish between responding and nonresponding tumors need to be validated for different systemic treatment approaches, with progression-free survival and overall survival as references. A PET-based treatment stratification is applicable clinically only if valid alternative therapies are available. Of note, patients who do not achieve a pCR might still benefit from neoadjuvant therapy enabling breast-conserving surgery. In the metastatic setting, residual tumor metabolic activity after the initiation of systemic therapy is an indicator of active disease, whereas a complete resolution of metabolic activity is predictive of a successful treatment response. PMID:26834099

  16. Prediction of Response to Medication and Cognitive Therapy in the Treatment of Moderate to Severe Depression

    PubMed Central

    Fournier, Jay C.; DeRubeis, Robert J.; Shelton, Richard C.; Hollon, Steven D.; Amsterdam, Jay D.; Gallop, Robert

    2009-01-01

    A recent randomized controlled trial found nearly equivalent response rates for antidepressant medications and cognitive therapy in a sample of moderate-to-severely depressed outpatients. In this article, we seek to identify the variables that were associated with response across both treatments as well as variables that predicted superior response in one treatment over the other. The sample consisted of 180 depressed outpatients: 60 of whom were randomly assigned to cognitive therapy; 120 were assigned to antidepressant medications. Treatment was provided for 16 weeks. Chronic depression, older age, and lower intelligence each predicted relatively poor response across both treatments. Three prescriptive variables were identified: marriage, unemployment, and having experienced a greater number of recent life events predicted superior response to cognitive therapy compared to antidepressant medications. Thus, six markers of treatment outcome were identified, each of which might be expected to carry considerable clinical utility. The three prognostic variables identify subgroups that might benefit from alternative treatment strategies; the three prescriptive variables identify groups who appear to respond particularly well to cognitive therapy. PMID:19634969

  17. Activation of phenotypic subpopulations in response to ciprofloxacin treatment in Acinetobacter baumannii.

    PubMed

    Macguire, Ashley E; Ching, Meining Carly; Diamond, Brett H; Kazakov, Alexey; Novichkov, Pavel; Godoy, Veronica G

    2014-04-01

    The multidrug-resistant, opportunistic pathogen, Acinetobacter baumannii, has spread swiftly through hospitals worldwide. Previously, we demonstrated that A. baumannii regulates the expression of various genes in response to DNA damage. Some of these regulated genes, especially those encoding the multiple error-prone DNA polymerases, can be implicated in induced mutagenesis, leading to antibiotic resistance. Here, we further explore the DNA damage-inducible system at the single cell level using chromosomal transcriptional reporters for selected DNA damage response genes. We found the genes examined respond in a bimodal fashion to ciprofloxacin treatment, forming two phenotypic subpopulations: induced and uninduced. This bimodal response to ciprofloxacin treatment in A. baumannii is unique and quite different than the Escherichia coli paradigm. The subpopulations are not genetically different, with each subpopulation returning to a starting state and differentiating with repeated treatment. We then identified a palindromic motif upstream of certain DNA damage response genes, and have shown alterations to this sequence to diminish the bimodal induction in response to DNA damaging treatment. Lastly, we are able to show a biological advantage for a bimodal response, finding that one subpopulation survives ciprofloxacin treatment better than the other. © 2014 John Wiley & Sons Ltd.

  18. Activation of Phenotypic Subpopulations in Response to Ciprofloxacin Treatment in Acinetobacter baumannii

    PubMed Central

    MacGuire, Ashley E.; Ching, Meining Carly; Diamond, Brett H.; Kazakov, Alexey; Novichkov, Pavel; Godoy, Veronica G.

    2014-01-01

    Summary The multidrug-resistant, opportunistic pathogen, Acinetobacter baumannii, has spread swiftly through hospitals worldwide. Previously, we demonstrated that A. baumannii regulates the expression of various genes in response to DNA damage. Some of these regulated genes, especially those encoding the multiple error-prone DNA polymerases, can be implicated in induced mutagenesis, leading to antibiotic resistance. Here, we further explore the DNA damage-inducible system at the single cell level using chromosomal transcriptional reporters for selected DNA damage response genes. We found the genes examined respond in a bimodal fashion to ciprofloxacin treatment, forming two phenotypic subpopulations: induced and uninduced. This bimodal response to ciprofloxacin treatment in A. baumannii is unique and quite different than the Escherichia coli paradigm. The subpopulations are not genetically different, with each subpopulation returning to a starting state and differentiating with repeated treatment. We then identified a palindromic motif upstream of certain DNA damage response genes, and have shown alterations to this sequence to diminish the bimodal induction in response to DNA damaging treatment. Lastly, we are able to show a biological advantage for a bimodal response, finding that one subpopulation survives ciprofloxacin treatment better than the other. PMID:24612352

  19. A systematic method for estimating individual responses to treatment with antipsychotics in CATIE

    PubMed Central

    Adkins, Daniel E.; McClay, Joseph; Lieberman, Jeffrey; Sullivan, Patrick F.

    2009-01-01

    Objective In addition to comparing drug treatment groups, the wealth of genetic and clinical data collected in the Clinical Antipsychotic Trials of Intervention Effectiveness study offers tremendous opportunities to study individual differences in response to treatment with antipsychotics. A major challenge, however, is how to estimate the individual responses to treatments. For this purpose, we propose a systematic method that condenses all information collected during the trials in an optimal, empirical fashion. Method Our method comprises three steps. First, we test how to best model treatment effects over time. Next, we screen many covariates to select those that will further improve the precision of the individual treatment effect estimates which, for example, improves power to detect predictors of individual treatment response. Third, Best Linear Unbiased Predictors (BLUPs) of the random effects are used to estimate for each individual a treatment effect based on the model empirically indicated to best fit the data. We illustrate our method for the Positive and Negative Syndrome Scale (PANSS). Results A model assuming it takes on average about 30 days for a treatment to exert an effect that will then remain about the same for the rest of the trial showed the best fit to the data. Of all screened covariates, only two improved the precision of the individual treatment effect estimates. A comparison with more traditional post- minus pre-treatment symptom scores showed that our model based treatment effect estimates were a) more precise because they use all data collected during the trial rather than just two data points, and b) less sensitive to biases created by using the same baseline to calculate multiple treatment effects in CATIE. Conclusions We demonstrate that treatment effects can be estimated in a way that condenses all information collected in an optimal, empirical fashion. We expect the proposed method to be valuable for other clinical outcomes in

  20. The impact of transient combination antiretroviral treatment in early HIV infection on viral suppression and immunologic response in later treatment.

    PubMed

    Pantazis, Nikos; Touloumi, Giota; Meyer, Laurence; Olson, Ashley; Costagliola, Dominique; Kelleher, Anthony D; Lutsar, Irja; Chaix, Marie-Laure; Fisher, Martin; Moreno, Santiago; Porter, Kholoud

    2016-03-27

    Effects of transient combination antiretroviral treatment (cART) initiated during early HIV infection (EHI) remain unclear. We investigate whether this intervention affects viral suppression and CD4 cell count increase following its reinitiation in chronic infection (CHI). Longitudinal observational study. We identified adult patients from Concerted Action of Seroconversion to AIDS and Death in Europe who seroconverted after 1/1/2000, had a 12 months or less HIV test interval and initiated cART from naive. We classified individuals as 'pretreated in EHI' if treated within 6 months of seroconversion, interrupted for at least 12 weeks, and reinitiated during CHI. Statistical analysis was performed using survival analysis methods and mixed models. Pretreated and initiated in CHI groups comprised 202 and 4263 individuals, with median follow-up after CHI treatment 4.5 and 3 years, respectively. Both groups had similar virologic response and relapse rates (P = 0.585 and P = 0.206) but pretreated individuals restarted treatment with higher baseline CD4 cell count (∼80 cells/μl; P < 0.001) and retained significantly higher CD4 cell count for more than 3 years after treatment (re)initiation. Assuming common baseline CD4 cell count, differences in CD4 cell count slopes were nonsignificant. Immunovirologic response to CHI treatment was not associated with timing or duration of the transient treatment. Although treatment interruptions are not recommended, stopping cART initiated in EHI does not seem to reduce the chance of a successful outcome of treatment in CHI.

  1. Rationale for the Application of Exposure Response Prevention to the Treatment of Anorexia Nervosa

    PubMed Central

    Steinglass, Joanna E.; Sysko, Robyn; Glasofer, Deborah; Albano, Anne Marie; Simpson, H. Blair; Walsh, B. Timothy

    2013-01-01

    Objective Anorexia nervosa (AN) is a life threatening and difficult to treat illness with a high relapse rate. Current treatments are inadequate and new approaches to treatment are needed. Method We review the data on anxiety in AN, the relationship between anxiety disorders and AN, and the use of Exposure and Response Prevention in treatment. Results The overlap between AN and anxiety disorders suggest a model of AN in which baseline anxiety features yield eating related fears, avoidance behaviors, and ritualized safety behaviors that promote the underweight state and the perpetuation of the disorder. We propose an Exposure and Response Prevention treatment to prevent relapse in AN. Discussion Overlap between AN and anxiety disorders suggests that Exposure and Response Prevention may be a new and beneficial approach to preventing relapse in individuals with AN. PMID:20127936

  2. Rationale for the application of exposure and response prevention to the treatment of anorexia nervosa.

    PubMed

    Steinglass, Joanna E; Sysko, Robyn; Glasofer, Deborah; Albano, Anne Marie; Simpson, H Blair; Walsh, B Timothy

    2011-03-01

    Anorexia nervosa (AN) is a life threatening and difficult to treat illness with a high relapse rate. Current treatments are inadequate and new approaches to treatment are needed. We review the data on anxiety in AN, the relationship between anxiety disorders and AN, and the use of Exposure and Response Prevention in treatment. The overlap between AN and anxiety disorders suggest a model of AN in which baseline anxiety features yield eating related fears, avoidance behaviors, and ritualized safety behaviors that promote the underweight state and the perpetuation of the disorder. We propose an Exposure and Response Prevention treatment to prevent relapse in AN. Overlap between AN and anxiety disorders suggests that Exposure and Response Prevention may be a new and beneficial approach to preventing relapse in individuals with AN. Copyright © 2009 Wiley Periodicals, Inc.

  3. The inoculum effect and band-pass bacterial response to periodic antibiotic treatment.

    PubMed

    Tan, Cheemeng; Smith, Robert Phillip; Srimani, Jaydeep K; Riccione, Katherine A; Prasada, Sameer; Kuehn, Meta; You, Lingchong

    2012-01-01

    The inoculum effect (IE) refers to the decreasing efficacy of an antibiotic with increasing bacterial density. It represents a unique strategy of antibiotic tolerance and it can complicate design of effective antibiotic treatment of bacterial infections. To gain insight into this phenomenon, we have analyzed responses of a lab strain of Escherichia coli to antibiotics that target the ribosome. We show that the IE can be explained by bistable inhibition of bacterial growth. A critical requirement for this bistability is sufficiently fast degradation of ribosomes, which can result from antibiotic-induced heat-shock response. Furthermore, antibiotics that elicit the IE can lead to 'band-pass' response of bacterial growth to periodic antibiotic treatment: the treatment efficacy drastically diminishes at intermediate frequencies of treatment. Our proposed mechanism for the IE may be generally applicable to other bacterial species treated with antibiotics targeting the ribosomes.

  4. Paradoxical response preceding control of Scedosporium apiospermum mycetoma with posaconazole treatment.

    PubMed

    Béraud, Guillaume; Desbois, Nicole; Coyo, Caroline; Quist, Danièle; Rozé, Benoit; Savorit, Luc; Cabié, André

    2015-01-01

    Mycetoma is a chronic granulomatous infection that is difficult to treat, notably when due to fungi such as Scedosporium apiospermum. Recent antifungal agents could be an option, but cases are rarely reported, and none with posaconazole. Paradoxical responses, defined as initial clinical worsening despite appropriate treatment, are common in tuberculosis but rare in deep mycoses in non-immunocompromised hosts. Hence, paradoxical responses in context other than mycobacterial infection in an immunocompromised host could provide insights into the pathophysiology and the optimal strategy for treatment. We report the first case of a mycetoma caused by S. apiospermum with bone involvement treated with posaconazole, and the paradoxical response observed at the beginning of the treatment. As with mycobacterial infections, a paradoxical response in deep mycosis could represent the earliest marker of therapeutic efficacy.

  5. Identifying a predictive model for response to atypical antipsychotic monotherapy treatment in south Indian schizophrenia patients.

    PubMed

    Gupta, Meenal; Moily, Nagaraj S; Kaur, Harpreet; Jajodia, Ajay; Jain, Sanjeev; Kukreti, Ritushree

    2013-08-01

    Atypical antipsychotic (AAP) drugs are the preferred choice of treatment for schizophrenia patients. Patients who do not show favorable response to AAP monotherapy are subjected to random prolonged therapeutic treatment with AAP multitherapy, typical antipsychotics or a combination of both. Therefore, prior identification of patients' response to drugs can be an important step in providing efficacious and safe therapeutic treatment. We thus attempted to elucidate a genetic signature which could predict patients' response to AAP monotherapy. Our logistic regression analyses indicated the probability that 76% patients carrying combination of four SNPs will not show favorable response to AAP therapy. The robustness of this prediction model was assessed using repeated 10-fold cross validation method, and the results across n-fold cross-validations (mean accuracy=71.91%; 95%CI=71.47-72.35) suggest high accuracy and reliability of the prediction model. Further validations of these results in large sample sets are likely to establish their clinical applicability.

  6. An examination of the Allocation of Treatment Responsibility scale in adolescents with epilepsy.

    PubMed

    Ryan, Jamie L; Arnett, Alex D; Pai, Ahna L H; Modi, Avani C

    2014-12-01

    The purpose of the current study was to examine the psychometric properties of the adapted Allocation of Treatment Responsibility (ATR) scale and the distribution of tasks related to oral medication and clinic and laboratory visits in a sample of adolescents with epilepsy. Adolescents with epilepsy (N = 50; ages 13-17 years) and their caregivers completed the adapted ATR and a measure of medication management. Internal consistency for the adapted ATR was strong (total and subscale range: 0.75-0.97). Validity was partially supported by significant correlations between adolescent age and ATR oral medication responsibility for both respondent measures. Allocation of Treatment Responsibility total scores were not associated with adherence to medications and clinic appointments. Initial findings are promising and have important implications for assessing the distribution of treatment responsibility among adolescents with epilepsy and their families. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. Purine and pyrimidine metabolism: Convergent evidence on chronic antidepressant treatment response in mice and humans

    PubMed Central

    Park, Dong Ik; Dournes, Carine; Sillaber, Inge; Uhr, Manfred; Asara, John M.; Gassen, Nils C.; Rein, Theo; Ising, Marcus; Webhofer, Christian; Filiou, Michaela D.; Müller, Marianne B.; Turck, Christoph W.

    2016-01-01

    Selective Serotonin Reuptake Inhibitors (SSRIs) are commonly used drugs for the treatment of psychiatric diseases including major depressive disorder (MDD). For unknown reasons a substantial number of patients do not show any improvement during or after SSRI treatment. We treated DBA/2J mice for 28 days with paroxetine and assessed their behavioral response with the forced swim test (FST). Paroxetine-treated long-time floating (PLF) and paroxetine-treated short-time floating (PSF) groups were stratified as proxies for drug non-responder and responder mice, respectively. Proteomics and metabolomics profiles of PLF and PSF groups were acquired for the hippocampus and plasma to identify molecular pathways and biosignatures that stratify paroxetine-treated mouse sub-groups. The critical role of purine and pyrimidine metabolisms for chronic paroxetine treatment response in the mouse was further corroborated by pathway protein expression differences in both mice and patients that underwent chronic antidepressant treatment. The integrated -omics data indicate purine and pyrimidine metabolism pathway activity differences between PLF and PSF mice. Furthermore, the pathway protein levels in peripheral specimens strongly correlated with the antidepressant treatment response in patients. Our results suggest that chronic SSRI treatment differentially affects purine and pyrimidine metabolisms, which may explain the heterogeneous antidepressant treatment response and represents a potential biosignature. PMID:27731396

  8. Improving Treatment Response for Paediatric Anxiety Disorders: An Information-Processing Perspective.

    PubMed

    Ege, Sarah; Reinholdt-Dunne, Marie Louise

    2016-12-01

    Cognitive behavioural therapy (CBT) is considered the treatment of choice for paediatric anxiety disorders, yet there remains substantial room for improvement in treatment outcomes. This paper examines whether theory and research into the role of information-processing in the underlying psychopathology of paediatric anxiety disorders indicate possibilities for improving treatment response. Using a critical review of recent theoretical, empirical and academic literature, the paper examines the role of information-processing biases in paediatric anxiety disorders, the extent to which CBT targets information-processing biases, and possibilities for improving treatment response. The literature reviewed indicates a role for attentional and interpretational biases in anxious psychopathology. While there is theoretical grounding and limited empirical evidence to indicate that CBT ameliorates interpretational biases, evidence regarding the effects of CBT on attentional biases is mixed. Novel treatment methods including attention bias modification training, attention feedback awareness and control training, and mindfulness-based therapy may hold potential in targeting attentional biases, and thereby in improving treatment response. The integration of novel interventions into an existing evidence-based protocol is a complex issue and faces important challenges with regard to determining the optimal treatment package. Novel interventions targeting information-processing biases may hold potential in improving response to CBT for paediatric anxiety disorders. Many important questions remain to be answered.

  9. TPH-2 Polymorphisms Interact with Early Life Stress to Influence Response to Treatment with Antidepressant Drugs

    PubMed Central

    Reynolds, Gavin P.; Yuan, Yonggui; Shi, Yanyan; Pu, Mengjia; Zhang, Zhijun

    2016-01-01

    Background: Variation in genes implicated in monoamine neurotransmission may interact with environmental factors to influence antidepressant response. We aimed to determine how a range of single nucleotide polymorphisms in monoaminergic genes influence this response to treatment and how they interact with childhood trauma and recent life stress in a Chinese sample. An initial study of monoaminergic coding region single nucleotide polymorphisms identified significant associations of TPH2 and HTR1B single nucleotide polymorphisms with treatment response that showed interactions with childhood and recent life stress, respectively (Xu et al., 2012). Methods: A total of 47 further single nucleotide polymorphisms in 17 candidate monoaminergic genes were genotyped in 281 Chinese Han patients with major depressive disorder. Response to 6 weeks’ antidepressant treatment was determined by change in the 17-item Hamilton Depression Rating Scale score, and previous stressful events were evaluated by the Life Events Scale and Childhood Trauma Questionnaire-Short Form. Results: Three TPH2 single nucleotide polymorphisms (rs11178998, rs7963717, and rs2171363) were significantly associated with antidepressant response in this Chinese sample, as was a haplotype in TPH2 (rs2171363 and rs1487278). One of these, rs2171363, showed a significant interaction with childhood adversity in its association with antidepressant response. Conclusions: These findings provide further evidence that variation in TPH2 is associated with antidepressant response and may also interact with childhood trauma to influence outcome of antidepressant treatment. PMID:27521242

  10. Sex differences in associations between cannabis craving and neural responses to cannabis cues: Implications for treatment.

    PubMed

    Wetherill, Reagan R; Jagannathan, Kanchana; Hager, Nathan; Childress, Anna Rose; Franklin, Teresa R

    2015-08-01

    Preclinical and clinical research indicates that there are sex differences in how men and women initiate, progress, respond to, and withdraw from cannabis use; however, neurophysiological differences, such as neural responses to cannabis cues, are not well understood. Using functional MRI and an event-related blood oxygen level-dependent backward-masking task, we compared neural responses to backward-masked cannabis cues to neutral cues in treatment-seeking, cannabis-dependent adults (N = 44; 27 males) and examined whether sex differences exist. In addition, functional MRI findings were correlated with cannabis craving. Backward-masked cannabis cues elicited greater neural responses than neutral cues in reward-related brain regions, including the striatum, hippocampus/amygdala, insula, anterior cingulate cortex, and lateral orbitofrontal cortex, p < .01, k > 121 voxels. Although no significant sex differences in neural responses to cannabis cues emerged, women showed a positive correlation between neural responses to cannabis cues in the bilateral insula and cannabis craving and an inverse correlation between neural responses to cannabis cues in the left lateral orbitofrontal cortex and cannabis craving. Men, however, showed a positive correlation between neural responses to cannabis cues in the striatum and cannabis craving. Given that cues and craving are important triggers and the focus on many behavioral treatment approaches, these findings suggest that treatment-seeking, cannabis-dependent men and women may benefit from sex-specific and tailored cannabis use disorder treatments.

  11. Bench to Bedside: Understanding Symptom Response to Acupuncture Treatment and Designing a Successful Acupuncture Treatment Program

    DTIC Science & Technology

    2015-10-01

    Illness, Complex Medical Illness, Acupuncture, Treatment Trial, Secondary Date Analysis 16. SECURITY CLASSIFICATION OF: U 17. LIMITATION OF...including fatigue, sleep and mood disturbances, cognitive dysfunction and musculoskeletal pain. Symptoms are often severe in intensity and interfere with...abdominal pain, depression, anxiety, temperature dysregulation, poor sleep , irregular menses, thirst, headache, fatigue, recurrent urinary tract

  12. Functional connectivity of the left DLPFC to striatum predicts treatment response of depression to TMS.

    PubMed

    Avissar, Michael; Powell, Fon; Ilieva, Irena; Respino, Matteo; Gunning, Faith M; Liston, Conor; Dubin, Marc J

    Repetitive transcranial magnetic stimulation (TMS) is a non-invasive, safe, and efficacious treatment for depression. TMS has been shown to normalize abnormal functional connectivity of cortico-cortical circuits in depression and baseline functional connectivity of these circuits predicts treatment response. Less is known about the relationship between functional connectivity of frontostriatal circuits and treatment response. We investigated whether baseline functional connectivity of distinct frontostriatal circuits predicted response to TMS. Resting-state fMRI (rsfMRI) was acquired in 27 currently depressed subjects with treatment resistant depression and 27 healthy controls. Depressed subjects were treated with 5 weeks of daily TMS over the left dorsolateral prefrontal cortex (DLPFC). The functional connectivity between limbic, executive, rostral motor, and caudal motor regions of frontal cortex and their corresponding striatal targets were determined at baseline using an existing atlas based on diffusion tensor imaging. TMS treatment response was measured by percent reduction in the 24-item Hamilton Depression Rating Scale (HAMD24). In an exploratory analysis, correlations were determined between baseline functional connectivity and TMS treatment response. Seven cortical clusters belonging to the executive and rostral motor frontostriatal projections had reduced functional connectivity in depression compared to healthy controls. No frontostriatal projections showed increased functional connectivity in depression (voxel-wise p < 0.01, family-wise α < 0.01). Only baseline functional connectivity between the left DLPFC and the striatum predicted TMS response. Higher baseline functional connectivity correlated with greater reductions in HAMD24 (Pearson's R = 0.58, p = 0.002). In an exploratory analysis, higher functional connectivity between the left DLPFC and striatum predicted better treatment response. Our findings suggest that the antidepressant

  13. Endovascular treatment of hepatocellular carcinoma with drug eluting microparticles (DC-Beads): CT evaluation of response to the treatment

    PubMed Central

    Boatta, Emanuele; Corona, Mario; Cannavale, Alessandro; Fanelli, Fabrizio; Cirelli, Carlo; de Medici, Lorenzo

    2013-01-01

    Background and Study Aims: Our aim was to assess the efficacy and tolerability of drug-eluting beads-transarterial chemoembolization (DEB-TACE) in the treatment of hepatocellular carcinoma (HCC), evaluating the response to the treatment after 1, 6, 12, and 24 months with multidetector computed tomography (MDCT) comparing European Association for the study of the Liver (EASL) and modified Response Evaluation Criteria in Solid Tumors (mRECIST) criteria. Materials and Methods: We enrolled 154 patients with uni- or multifocal HCC who underwent a DEB-TACE. A total of 278 HCC nodules were treated. CT follow-up was performed at 1, 6, 12, and 24 months after the procedure according to the EASL and RECIST criteria evaluating overall target and target nodule response. We also analyzed the shrinking of nodules in relation to response to treatment. Results: A total of 278 nodules of HCC underwent TACE by using DC-Beads: At 24, months complete response was similar for EASL and RECIST criteria (112 vs. 121 nodules) with optimal accordance between methods and readers with k = 0.9. Partial Response resulted significantly different among the two methods within the first month, otherwise was similar after 24-month follow-up. Similar results in both methods were found for nodules classified as Stable Disease (P > 0.05). Progressive Disease results were similar in both the groups according to both the classification criteria without any significant difference (P > 0.05). Conclusion: Our study confirmed that EASL and mRECIST criteria are both effective methods for patient follow-up, however with some technical differences. PMID:24082476

  14. Immune response profiling in early rheumatoid arthritis: discovery of a novel interaction of treatment response with viral immunity

    PubMed Central

    2013-01-01

    Introduction It remains challenging to predict the outcomes of therapy in patients with rheumatoid arthritis (RA). The objective of this study was to identify immune response signatures that correlate with clinical treatment outcomes in patients with RA. Methods A cohort of 71 consecutive patients with early RA starting treatment with disease-modifying antirheumatic drugs (DMARDs) was recruited. Disease activity at baseline and after 21 to 24 weeks of follow-up was measured using the Disease Activity Score in 28 joints (DAS28). Immune response profiling was performed by analyzing multi-cytokine production from peripheral blood cells following incubation with a panel of stimuli, including a mixture of human cytomegalovirus (CMV) and Epstein-Barr virus (EBV) lysates. Profiles identified via principal components analysis (PCA) for each stimulus were then correlated with the ΔDAS28 from baseline to follow-up. A clinically meaningful improvement in the DAS28 was defined as a decrease of ≥1.2. Results A profile of T-cell cytokines (IL-13, IL-4, IL-5, IL-2, IL-12, and IFN-γ) produced in response to CMV/EBV was found to correlate with the ΔDAS28 from baseline to follow-up. At baseline, a higher magnitude of the CMV/EBV immune response profile predicted inadequate DAS28 improvement (mean PCA-1 scores: 65.6 versus 50.2; P = 0.029). The baseline CMV/EBV response was particularly driven by IFN-γ (P = 0.039) and IL-4 (P = 0.027). Among patients who attained clinically meaningful DAS28 improvement, the CMV/EBV PCA-1 score increased from baseline to follow-up (mean +11.6, SD 25.5), whereas among patients who responded inadequately to DMARD therapy, the CMV/EBV PCA-1 score decreased (mean -12.8, SD 25.4; P = 0.002). Irrespective of the ΔDAS28, methotrexate use was associated with up-regulation of the CMV/EBV response. The CMV/EBV profile was associated with positive CMV IgG (P <0.001), but not EBV IgG (P = 0.32), suggesting this response was related to

  15. Artificial neural network model for the prediction of obsessive-compulsive disorder treatment response.

    PubMed

    Salomoni, Giuliana; Grassi, Massimiliano; Mosini, Paola; Riva, Patrizia; Cavedini, Paolo; Bellodi, Laura

    2009-08-01

    Several patients with obsessive-compulsive disorder (OCD) who are refractory to adequate treatment with first-line treatments are considered treatment-resistant. Further surveys were to be implemented to explore the outcome predictors of the antiobsessional response. Such study was aimed at building a model suitable to predict the final outcome of a mixed OCD pharmacologic and nonpharmacologic treatment approaches. We studied 130 subjects with OCD who underwent pharmacologic (with selective serotonin reuptake inhibitors alone or with selective serotonin reuptake inhibitors and risperidone at low dosage) and/or behavioral therapy (using exposure and response prevention techniques). The following variables were used as predictors: symptoms dimension, as resulting from the Yale-Brown Obsessive-Compulsive Scale items factor analysis; neuropsychologic performances; and epidemiologic variables. The treatment response arising from 3 to 6 months of therapy was used as dependent variable. A conventional logistic regression was used to define a previsional model of treatment response and multilayer perceptrons and to supervise an artificial neural network technique. The 46.9% of the sample resulted to be refractory to treatment. Results obtained with the logistic regression model showed that the only predictors of treatment outcome are hoarding symptoms, repeating rituals, and counting compulsions. Furthermore, using all the variables considered in the models, multilayer perceptrons showed highly better predictive performance as compared with the logistic regression models (93.3% vs 61.5%, respectively, of correct classification of cases). Complex interactions between different clinical and neuropsychologic variables are involved in defining OCD treatment response profile, and nonlinear and interactive modeling strategies, that is, supervised artificial neural networks, seem to be more suitable to investigate this complexity than linear techniques.

  16. Immunoadsorption in patients with chronic inflammatory demyelinating polyradiculoneuropathy with unsatisfactory response to first-line treatment.

    PubMed

    Galldiks, Norbert; Burghaus, Lothar; Dohmen, Christian; Teschner, Sven; Pollok, Manfred; Leebmann, Josef; Frischmuth, Nikolaus; Hollinger, Peter; Nazli, Nahed; Fassbender, Cordula; Klingel, Reinhard; Benzing, Thomas; Fink, Gereon R; Haupt, Walter F

    2011-01-01

    First-line treatment options for chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) are corticosteroids, intravenous immunoglobulin, and plasma exchange. In a significant number of patients, first-line therapy fails, and long-term maintenance treatment still remains a therapeutic challenge. Immunoadsorption (IA) may be an alternative to classical plasma exchange in the therapy of immune-mediated neurologic diseases. The aim of this investigation was to evaluate efficacy and safety of IA in patients with CIDP with unsatisfactory response to first-line treatment options. CIDP patients received adjunct IA treatment using tryptophan-immune adsorbers. The inflammatory neuropathy cause and treatment disability (INCAT) score was used to grade disability and monitor treatment effects. In total, 14 CIDP patients were analyzed. Ten patients were treated in hospital. After one IA treatment series, the INCAT score decreased significantly in all 10 patients. Four of these 14 patients were treated in outpatient clinics using long-term maintenance IA with 1-2 treatments per week. In these 4 patients, effects of long-term maintenance IA resulted in an improvement of overall disability. In all patients, IA was safe, well tolerated, and no severe adverse effects occurred. IA could be an effective and safe option for CIDP patients with unsatisfactory response to first-line treatment options and for long-term maintenance treatment. Copyright © 2011 S. Karger AG, Basel.

  17. Body mass index and response to a multidisciplinary treatment of fibromyalgia.

    PubMed

    Castel, Antoni; Castro, Sonia; Fontova, Ramon; Poveda, Maria José; Cascón-Pereira, Rosalia; Montull, Salvador; Padrol, Anna; Qanneta, Rami; Rull, Maria

    2015-02-01

    The purpose of this study is to determine whether there are some differences in the treatment responses to a multidisciplinary fibromyalgia (FM) treatment related with the baseline body mass index (BMI) of the participants. Inclusion criteria consisted of female sex, a diagnosis of FM (American College of Rheumatology criteria), age between 18 and 60 years, and between 3 and 8 years of schooling. Baseline BMI was determined, and patients were randomly assigned to one of the two treatment conditions: conventional pharmacologic treatment or multidisciplinary treatment. Outcome measures were pain intensity, functionality, catastrophizing, psychological distress, health-related quality of life, and sleep disturbances. One hundred thirty patients participated in the study. No statistical significant differences regarding pre-treatment outcomes were found among the different BMI subgroups, and between the two experimental conditions for each BMI category. General linear model analysis showed a significant interaction group treatment × time in pain intensity (p < .01), functionality (p < .0001), catastrophizing (p < .01), psychological distress (p < .0001), sleep index problems (p < .0001), and health-related quality of life (p < .05). No significant interactions were found in BMI × time, and in BMI × group treatment × time. There are not differences among normal weight, overweight and obese patients with FM regarding their response to a multidisciplinary treatment programme for FM which combines pharmacological treatment, education, physical therapy and cognitive behavioural therapy.

  18. Affect Following First Exercise Session as a Predictor of Treatment Response in Depression.

    PubMed

    Suterwala, Anisha M; Rethorst, Chad D; Carmody, Thomas J; Greer, Tracy L; Grannemann, Bruce D; Jha, Manish; Trivedi, Madhukar H

    2016-08-01

    Remission rates are low with first-step or even second-step antidepressant treatments. Furthermore, despite extensive investments from National Institutes of Health and from industry, novel treatments are not yet available in clinical care for depression. Predictors of treatment response very early in the course of treatment can avoid unnecessarily lengthy trials with ineffective treatments and reduce the trial and error process. This article examines the expression of positive affect immediately following an acute exercise session at the end of the first exercise session as a predictor of treatment response in the National Institute of Mental Health-funded TREAD (Treatment with Exercise Augmentation for Depression) study, which was conducted from April 2003 to August 2007. 122 subjects with DSM-IV-diagnosed major depressive disorder were randomized to public health dose (16 kcal/kg/wk) or low dose (4 kcal/kg/wk) of exercise for 12 weeks. Affect following the first exercise session was assessed using the Positive and Negative Affect Scale (PANAS), and depressive symptoms were assessed weekly using the Inventory of Depressive Symptomatology, Clinician Rating (IDS-C) (primary outcome measure). The PANAS composite affect score (positive-negative total) predicted change in IDS-C score (P < .05), as well as treatment response (P < .02) and remission (P < .03) for those in the high-dose group but not in the low-dose group. These findings suggest that the composite positive affect following the first exercise session has clinical utility to predict treatment response to exercise in depression and match the "right patient" with the "right" treatment. ClinicalTrials.gov identifier: NCT00076258. © Copyright 2016 Physicians Postgraduate Press, Inc.

  19. Immediate skin responses to laser and light treatments: Warning endpoints: How to avoid side effects.

    PubMed

    Wanner, Molly; Sakamoto, Fernanda H; Avram, Mathew M; Anderson, R Rox

    2016-05-01

    Lasers are versatile, commonly used treatment tools in dermatology. While it is tempting to follow manufacturer's guidelines or other "recipes" for laser treatment, this approach alone can be a recipe for disaster. Specific and immediate skin responses or endpoints exist and are clinically useful because they correlate with underlying mechanisms that are either desirable (ie, therapeutic), undesirable (ie, warning signs of injury or side effects), or incidental. The observation of clinical endpoints is a safe and reliable guide for appropriate treatment. This article presents the warning endpoints during specific dermatologic laser treatments, and the accompanying article presents the therapeutic endpoints, their underlying mechanisms, and the utility of these endpoints.

  20. Clinical and immunological response to photodynamic therapy in the treatment of vulval intraepithelial neoplasia.

    PubMed

    Daayana, S; Winters, U; Stern, P L; Kitchener, H C

    2011-05-01

    Vulval intraepithelial neoplasia (VIN) is a premalignant condition of the vulva and its incidence is increasing. The common type of VIN is associated with oncogenic types of human papilloma virus (HPV) infection. The standard modalities of treatment for VIN, surgical excision and laser ablation, are both sub-optimal, associated with high rates of disease recurrence. There is a need for non-surgical treatment options for VIN and photodynamic therapy (PDT), by altering the local immunological parameters, has the potential to clear both VIN and HPV. This article reviews the studies of PDT treatment for VIN and discusses the clinical and immunological responses to PDT treatment in the various studies.

  1. Oral Appliance Treatment Response and Polysomnographic Phenotypes of Obstructive Sleep Apnea

    PubMed Central

    Sutherland, Kate; Takaya, Hisashi; Qian, Jin; Petocz, Peter; Ng, Andrew T.; Cistulli, Peter A.

    2015-01-01

    Study Objectives: Mandibular advancement splints (MAS) are an effective treatment for obstructive sleep apnea (OSA); however, therapeutic response is variable. Younger age, female gender, less obesity, and milder and supine-dependent OSA have variably been associated with treatment success in relatively small samples. Our objective was to utilize a large cohort of MAS treated patients (1) to compare efficacy across patients with different phenotypes of OSA and (2) to assess demographic, anthropometric, and polysomnography variables as treatment response predictors. Methods: Retrospective analysis of MAS-treated patients participating in clinical trials in sleep centers in Sydney, Australia between years 2000–2013. All studies used equivalent customized two-piece MAS devices and treatment protocols. Treatment response was defined as (1) apnea-hypopnea index (AHI) < 5/h, (2) AHI < 10/h and ≥ 50% reduction, and (3) ≥ 50% AHI reduction. Results: A total of 425 patients (109 female) were included (age 51.2 ± 10.9 years, BMI 29.2 ± 5.0 kg/m2). MAS reduced AHI by 50.3% ± 50.7% across the group. Supine-predominant OSA patients had lower treatment response rates than non-positional OSA (e.g., 36% vs. 59% for AHI < 10/h). REM-predominant OSA showed a lower response rate than either NREM or non-stage dependent OSA. In prediction modelling, age, baseline AHI, and anthropometric variables were predictive of MAS treatment outcome but not OSA phenotype. Gender was not associated with treatment outcome. Conclusions: Lower MAS treatment response rates were observed in supine and REM sleep. In a large sample, we confirm that demographic, anthropometric, and polysomnographic data only weakly inform about MAS efficacy, supporting the need for alternative objective prediction methods to reliably select patients for MAS treatment. Citation: Sutherland K, Takaya H, Qian J, Petocz P, Ng AT, Cistulli PA. Oral appliance treatment response and polysomnographic phenotypes of

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

    PubMed

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

    2015-05-01

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

  3. Religiosity and treatment response to antidepressant medication: A prospective multi-site clinical trial

    PubMed Central

    Schettino, Jonathan R.; Olmos, Natasha T.; Myers, Hector F.; Joseph, Nataria T.; Poland, Russell E.; Lesser, Ira M.

    2012-01-01

    The present study examined the relationship between religiosity/spirituality and treatment response to antidepressant medication (citalopram). One-hundred and forty-eight Caucasian and African-American adults with uncomplicated major depression were treated with citalopram (20–60mg/day) over an 8-week period in a prospective multi-site clinical trial. Treatment response was assessed weekly with the Hamilton Rating Scale for Depression. Religiosity (i.e., religious behaviours) and spirituality (i.e., spiritual well-being) were assessed at Week 3. No significant associations between spirituality and treatment response were found; however, there was a strong curvilinear relationship between religiosity and treatment response. Compared to lower or higher levels of religiosity, a moderate level of religiosity was significantly associated with a higher likelihood of remission and greater reduction in severity of depression. This association was independent of social support, ethnicity, gender, education, and baseline depression severity. A moderate amount of religiosity appears to be independently associated with an enhanced treatment response to citalopram. PMID:22736954

  4. Lamivudine treatment can restore T cell responsiveness in chronic hepatitis B.

    PubMed Central

    Boni, C; Bertoletti, A; Penna, A; Cavalli, A; Pilli, M; Urbani, S; Scognamiglio, P; Boehme, R; Panebianco, R; Fiaccadori, F; Ferrari, C

    1998-01-01

    High viral and/or antigen load may be an important cause of the T cell hyporesponsiveness to hepatitis B virus (HBV) antigens that is often observed in patients with chronic HBV infection. Reduction of viral and antigen load by lamivudine treatment represents an ideal model for investigating this hypothesis. HLA class II restricted T cell responses and serum levels of HBV-DNA, HBsAg, and HBeAg were studied before and during lamivudine treatment in 12 patients with hepatitis B e antigen positive chronic active hepatitis B to assess possible correlations between viral and/or antigen load and vigor of the T cell response. Cell proliferation to HBV nucleocapsid antigens and peptides and frequency of circulating HBV nucleocapsid-specific T cells were assessed to characterize CD4-mediated responses. A highly significant enhancement of the CD4-mediated response to HBV nucleocapsid antigens was already detectable in most patients 7-14 d after the start of lamivudine treatment. This effect was dramatic and persistent in 10 patients but undetectable in 2. It occurred concomitant with a rapid and marked reduction of viremia. Interestingly, lamivudine also enhanced the responses to mitogens and recall antigens, showing that its effect was not limited to HBV-specific T cells. In conclusion, an efficient antiviral T cell response can be restored by lamivudine treatment in patients with chronic hepatitis B concurrently with reduction of viremia, indicating the importance of viral load in the pathogenesis of T cell hyporesponsiveness in these patients. Since lamivudine treatment can overcome T cell hyporeactivity, combining lamivudine with treatments directed to stimulate the T cell response may represent an effective strategy to induce eradication of chronic HBV infection. PMID:9727065

  5. Serial diffusion MRI to monitor and model treatment response of the targeted nanotherapy CRLX101

    PubMed Central

    Ng, Thomas S.C.; Wert, David; Sohi, Hargun; Procissi, Daniel; Colcher, David; Raubitschek, Andrew A.; Jacobs, Russell E.

    2013-01-01

    Purpose Targeted nanotherapies are being developed to improve tumor drug delivery and enhance therapeutic response. Techniques that can predict response will facilitate clinical translation and may help define optimal treatment strategies. We evaluated the efficacy of diffusion-weighted magnetic resonance imaging to monitor early response to CRLX101 nanotherapy (formerly IT-101), and explored its potential as a therapeutic response predictor using a mechanistic model of tumor cell-proliferation. Experimental Design Diffusion MRI was serially performed following CRLX101 administration in a mouse lymphoma model. Apparent diffusion coefficients (ADC) extracted from the data were used as treatment response biomarkers. Animals treated with irinotecan (CPT-11) and saline were imaged for comparison. ADC data were also input into a mathematical model of tumor growth. Histological analysis using cleaved-caspase 3, TUNEL, Ki-67 and H&E were conducted on tumor samples for correlation with imaging results. Results CRLX101 treated tumors at day 2, 4, 7 post-treatment exhibited changes in mean ADC=16 ± 9%, 24 ± 10% 49 ± 17% and size (TV)=−5 ± 3%, −30 ± 4% and −45 ± 13% respectively. Both parameters were statistically greater than controls (p(ADC) ≤ 0.02, and p(TV) ≤ 0.01 at day 4 and 7), and noticeably greater than CPT-11 treated tumors (ADC=5 ± 5%, 14 ± 7% and 18 ± 6%, TV=−15 ± 5%, −22 ± 13% and −26 ± 8%). Model-derived parameters for cell-proliferation obtained using ADC data distinguished CRLX101 treated tumors from controls (p = 0.02). Conclusions Temporal changes in ADC specified early CRLX101 treatment response and could be used to model image-derived cell-proliferation rates following treatment. Comparisons of targeted and non-targeted treatments highlight the utility of non-invasive imaging and modeling to evaluate, monitor and predict responses to targeted nanotherapeutics. PMID:23532891

  6. CT contrast predicts pancreatic cancer treatment response to verteporfin-based photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Jermyn, Michael; Davis, Scott C.; Dehghani, Hamid; Huggett, Matthew T.; Hasan, Tayyaba; Pereira, Stephen P.; Bown, Stephen G.; Pogue, Brian W.

    2014-04-01

    The goal of this study was to determine dominant factors affecting treatment response in pancreatic cancer photodynamic therapy (PDT), based on clinically available information in the VERTPAC-01 trial. This trial investigated the safety and efficacy of verteporfin PDT in 15 patients with locally advanced pancreatic adenocarcinoma. CT scans before and after contrast enhancement from the 15 patients in the VERTPAC-01 trial were used to determine venous-phase blood contrast enhancement and this was correlated with necrotic volume determined from post-treatment CT scans, along with estimation of optical absorption in the pancreas for use in light modeling of the PDT treatment. Energy threshold contours yielded estimates for necrotic volume based on this light modeling. Both contrast-derived venous blood content and necrotic volume from light modeling yielded strong correlations with observed necrotic volume (R2 = 0.85 and 0.91, respectively). These correlations were much stronger than those obtained by correlating energy delivered versus necrotic volume in the VERTPAC-01 study and in retrospective analysis from a prior clinical study. This demonstrates that contrast CT can provide key surrogate dosimetry information to assess treatment response. It also implies that light attenuation is likely the dominant factor in the VERTPAC treatment response, as opposed to other factors such as drug distribution. This study is the first to show that contrast CT provides needed surrogate dosimetry information to predict treatment response in a manner which uses standard-of-care clinical images, rather than invasive dosimetry methods.

  7. Implicit processes in pathological skin picking: responses to skin irregularities predict symptom severity and treatment susceptibility.

    PubMed

    Schuck, Kathrin; Keijsers, Ger; Rinck, Mike

    2012-03-01

    Implicit cognitive processes are relevant in understanding the development and maintenance of psychopathology and dysfunctional behaviours. The present study investigated the role of implicit processes in pathological skin picking (PSP). Using an Approach-Avoidance Task (AAT), we examined automatic response tendencies towards skin picking-related photographs in a sample of 34 college students who suffered from PSP and participated in a randomized, waiting-list controlled treatment study. In comparison to a control sample (n = 49), PSP patients displayed significantly decelerated reaction times (distraction) in response to photographs of skin irregularities and a tendency to respond with avoidance to photographs of skin irregularities. Both distraction and avoidance in reaction to photographs of skin irregularities were significantly associated with current skin picking severity. Moreover, the strength of distraction in response to skin irregularities predicted unique variance in skin picking severity at post-measurement, over and above the effect of skin picking severity at pre-measurement and the effect of treatment condition. For the treatment condition, higher initial distraction predicted better treatment outcome (lower skin picking severity at post-measurement), whereas it predicted symptom deterioration at post-treatment for untreated participants. The specific characteristics of PSP patients (mainly female university students) and the relatively small sample size may compromise generalizability of findings. In PSP, affective distraction in response to skin irregularities seems to characterize an important process related to symptom severity as well as treatment susceptibility. Copyright © 2011 Elsevier Ltd. All rights reserved.

  8. Pharmacogenetics of clozapine treatment response and side-effects in schizophrenia: an update.

    PubMed

    Sriretnakumar, Venuja; Huang, Eric; Müller, Daniel J

    2015-01-01

    Clozapine (CLZ) is the most effective treatment for treatment-resistant schizophrenia (SCZ) patients, with potential added benefits of reduction in suicide risk and aggression. However, CLZ is also mainly underused due to its high risk for the potentially lethal side-effect of agranulocytosis as well as weight gain and related metabolic dysregulation. Pharmacogenetics promises to enable the prediction of patient treatment response and risk of adverse effects based on patients' genetics, paving the way toward individualized treatment. This article reviews pharmacogenetics studies of CLZ response and side-effects with a focus on articles from January 2012 to February 2015, as an update to the previous reviews. Pharmacokinetic genes explored primarily include CYP1A2, while pharmacodynamic genes consisted of traditional pharmacogenetic targets such as brain-derived neurotrophic factor as well novel mitochondrial genes, NDUFS-1 and translocator protein. Pharmacogenetics is a promising avenue for individualized medication of CLZ in SCZ, with several consistently replicated gene variants predicting CLZ response and side-effects. However, a large proportion of studies have yielded mixed results. Large-scale Genome-wide association studies (e.g., CRESTAR) and targeted gene studies with standardized designs (response measurements, treatment durations, plasma level monitoring) are required for further progress toward clinical translation. Additionally, in order to improve study quality, we recommend accounting for important confounders, including polypharmacy, baseline measurements, treatment duration, gender, and age at onset.

  9. Intravoxel incoherent motion (IVIM) histogram biomarkers for prediction of neoadjuvant treatment response in breast cancer patients.

    PubMed

    Cho, Gene Y; Gennaro, Lucas; Sutton, Elizabeth J; Zabor, Emily C; Zhang, Zhigang; Giri, Dilip; Moy, Linda; Sodickson, Daniel K; Morris, Elizabeth A; Sigmund, Eric E; Thakur, Sunitha B

    2017-01-01

    To examine the prognostic capabilities of intravoxel incoherent motion (IVIM) metrics and their ability to predict response to neoadjuvant treatment (NAT). Additionally, to observe changes in IVIM metrics between pre- and post-treatment MRI. This IRB-approved, HIPAA-compliant retrospective study observed 31 breast cancer patients (32 lesions). Patients underwent standard bilateral breast MRI along with diffusion-weighted imaging before and after NAT. Six patients underwent an additional IVIM-MRI scan 12-14 weeks after initial scan and 2 cycles of treatment. In addition to apparent diffusion coefficients (ADC) from monoexponential decay, IVIM mean values (tissue diffusivity Dt, perfusion fraction fp, and pseudodiffusivity Dp) and histogram metrics were derived using a biexponential model. An additional filter identified voxels of highly vascular tumor tissue (VTT), excluding necrotic or normal tissue. Clinical data include histology of biopsy and clinical response to treatment through RECIST assessment. Comparisons of treatment response were made using Wilcoxon rank-sum tests. Average, kurtosis, and skewness of pseudodiffusion Dp significantly differentiated RECIST responders from nonresponders. ADC and Dt values generally increased (∼70%) and VTT% values generally decreased (∼20%) post-treatment. Dp metrics showed prognostic capabilities; slow and heterogeneous pseudodiffusion offer poor prognosis. Baseline ADC/Dt parameters were not significant predictors of response. This work suggests that IVIM mean values and heterogeneity metrics may have prognostic value in the setting of breast cancer NAT.

  10. Genetic polymorphisms, their allele combinations and IFN-β treatment response in Irish multiple sclerosis patients

    PubMed Central

    O’Doherty, Catherine; Favorov, Alexander; Heggarty, Shirley; Graham, Colin; Favorova, Olga; Ochs, Michael; Hawkins, Stanley; Hutchinson, Michael; O’Rourke, Killian; Vandenbroeck, Koen

    2009-01-01

    Introduction IFN-β is widely used as first-line immunomodulatory treatment for multiple sclerosis. Response to treatment is variable (30–50% of patients are nonresponders) and requires a long treatment duration for accurate assessment to be possible. Information about genetic variations that predict responsiveness would allow appropriate treatment selection early after diagnosis, improve patient care, with time saving consequences and more efficient use of resources. Materials & methods We analyzed 61 SNPs in 34 candidate genes as possible determinants of IFN-β response in Irish multiple sclerosis patients. Particular emphasis was placed on the exploration of combinations of allelic variants associated with response to therapy by means of a Markov chain Monte Carlo-based approach (APSampler). Results The most significant allelic combinations, which differed in frequency between responders and nonresponders, included JAK2–IL10RB–GBP1–PIAS1 (permutation p-value was pperm = 0.0008), followed by JAK2–IL10–CASP3 (pperm = 0.001). Discussion The genetic mechanism of response to IFN-β is complex and as yet poorly understood. Data mining algorithms may help in uncovering hidden allele combinations involved in drug response versus nonresponse. PMID:19604093

  11. Breeding bird responses to three silvicultural treatments in the Oregon Coast Range

    USGS Publications Warehouse

    Chambers, C.L.; McComb, W.C.; Tappeiner, J. C.

    1999-01-01

    Silvicultural alternatives to clear-cutting have been suggested to promote development, retention, or creation of late-successional features such as large trees, multilayered canopies, snags, and logs. We assessed bird response to three silvicultural alternatives to clear-cutting that retained structural features found in old Douglas-fir (Pseudotsuga menziesii) forests and that imitated natural disturbance regimes more closely than did traditional clear-cutting: (1) small-patch group selection treatment representing a low-intensity disturbance; (2) two-story treatment, representing a moderate to high-intensity disturbance; and (3) modified clear-cut treatment, representing a high-intensity disturbance. We counted diurnal breeding birds 1 yr prior to and 2 yr after harvest to estimate effects of the silvicultural treatments on bird communities compared with uncut controls. The small-patch group selection treatment was most similar in species composition to control stands. The two-story treatment was more similar to the modified clear-cut treatment. Ten bird species remained abundant following the small-patch group selection treatment. They declined in abundance in modified clearcuts and two-story stands. These species included four neotropical migratory species and five species with restricted geographic ranges and habitat associations. Nine species increased in response to moderate and/or high-intensity disturbances. This group included a larger proportion of species that were habitat generalists. Silvicultural treatments imitating low-intensity disturbances were most effective in retaining bird communities associated with mature forest; high-intensity disturbances such as the two-story and modified clear-cut treatments greatly altered bird community composition. Bird responses to the silvicultural treatments that we studied indicate that a variety of stand types is needed to meet needs of all species.

  12. Severity of depression and anxiety are predictors of response to antidepressant treatment in Parkinson's disease.

    PubMed

    Moonen, A J H; Wijers, A; Leentjens, A F G; Christine, C W; Factor, S A; Juncos, J; Lyness, J M; Marsh, L; Panisset, M; Pfeiffer, R; Rottenberg, D; Serrano Ramos, C; Shulman, L; Singer, C; Slevin, J; McDonald, W; Auinger, P; Richard, I H

    2014-06-01

    Antidepressants have appeared to be more effective than placebo treatment in treating depressive syndromes in patients with Parkinson's disease (PD). To identify factors that predict improvement in depressive symptoms during antidepressant treatment in depressed PD patients. A secondary analysis was performed on the dataset of the Randomized Placebo-controlled Study of Antidepressants in PD (SAD-PD), in which 76 patients received active treatment with either paroxetine or venlafaxine extended release (XR), and 39 patients received placebo treatment. Backward stepwise regression analyses were conducted with change in 24-item Hamilton Depression Rating Scale (HAMD-24) score between assessments at baseline and week 12 as the main outcome measure, and sex, age, baseline HAMD-24 score, Unified Parkinson's Disease Rating Scale section III (UPDRS-III) score, Mini-Mental State Examination (MMSE), and the Clinical Anxiety Scale (CAS) as independent variables. In both the active treatment and placebo groups, higher baseline HAMD-24 score and lower UPDRS-III score were associated with greater reduction in HAMD-24 score. Higher anxiety scores predicted less response in the active treatment group. Higher MMSE scores predicted greater response only in the placebo-treated group. Sex and age were no predictors of response. Higher pre-treatment depression scores and lower pre-treatment anxiety scores are the two most important predictors for improvement during antidepressant treatment in depressed PD patients, which is in line with those found in treatment studies of depressed non-PD patients. Furthermore, our results indicate the requirement for different or more intensive treatment for depressed PD patients with more severe anxiety symptoms. Copyright © 2014 Elsevier Ltd. All rights reserved.

  13. Reevaluating response and failure of medical treatment of endometriosis: a systematic review.

    PubMed

    Becker, Christian M; Gattrell, William T; Gude, Kerstin; Singh, Sukhbir S

    2017-07-01

    To assess patient response rates to medical therapies used to treat endometriosis-associated pain. A systematic review with the use of Medline and Embase. Not applicable. Women receiving medical therapy to treat endometriosis. None. The proportions of patients who: experienced no reduction in endometriosis-associated pain symptoms; had pain symptoms remaining at the end of the treatment period; had pain recurrence after treatment cessation; experienced an increase or no change in disease score during the study; were satisfied with treatment; and discontinued therapy owing to adverse events or lack of efficacy. The change in pain symptom severity experienced during and after treatment, as measured on the visual analog scale, was also assessed. In total, 58 articles describing 125 treatment arms met the inclusion criteria. Data for the response of endometriosis-associated pain symptoms to treatment were presented in only 29 articles. The median proportions of women with no reduction in pain were 11%-19%; at the end of treatment, 5%-59% had pain remaining; and after follow-up, 17%-34% had experienced recurrence of pain symptoms after treatment cessation. After median study durations of 2-24 months, the median discontinuation rates due to adverse events or lack of efficacy were 5%-16%. Few studies of medical therapies for endometriosis report outcomes that are relevant to patients, and many women gain only limited or intermittent benefit from treatment. Copyright © 2017. Published by Elsevier Inc.

  14. Relationship satisfaction as a predictor of treatment response during cognitive behavioral sex therapy.

    PubMed

    Stephenson, Kyle R; Rellini, Alessandra H; Meston, Cindy M

    2013-01-01

    Although recent research suggests that individual cognitive behavioral therapy (CBT) may be an effective treatment for female sexual dysfunctions, we have little information regarding predictors of treatment response. The goal of the current study was to assess the degree to which pre-treatment relationship satisfaction predicted treatment response to cognitive behavioral sex therapy. Women with sexual dysfunction (n = 31, M age = 28 years, 77.4 % Caucasian) receiving cognitive-behavioral sex therapy with or without ginkgo biloba, as part of a wider randomized clinical trial, were assessed pre- and post-treatment using validated self-report measures of sexual satisfaction, sexual distress, sexual functioning, and relationship satisfaction. Pre-treatment relationship satisfaction predicted changes in sexual satisfaction and distress, but not sexual functioning. Women with higher relationship satisfaction at intake experienced larger gains in sexual satisfaction and distress over the course of treatment. Pre-treatment relationship satisfaction also moderated the association between changes in sexual functioning and changes in sexual distress, such that improved functioning was associated with decreased distress only for women entering therapy with high relationship satisfaction. These findings suggest that, for women with low relationship satisfaction before entering treatment, improvement in sexual functioning may not be enough to alleviate their sexual distress.

  15. Time to Response to Citalopram Treatment for Agitation in Alzheimer Disease.

    PubMed

    Weintraub, Daniel; Drye, Lea T; Porsteinsson, Anton P; Rosenberg, Paul B; Pollock, Bruce G; Devanand, Devangere P; Frangakis, Constantine; Ismail, Zahinoor; Marano, Christopher; Meinert, Curtis L; Mintzer, Jacobo E; Munro, Cynthia A; Pelton, Gregory; Rabins, Peter V; Schneider, Lon S; Shade, David M; Yesavage, Jerome; Lyketsos, Constantine G

    2015-11-01

    Agitation is a common and significant problem in Alzheimer disease (AD). In the recent Citalopram for Agitation in Alzheimer's Disease (CitAD) study, citalopram was efficacious for the treatment of AD agitation. Here we examined the time course and predictors of response to treatment. Response in CitAD was defined as a modified Alzheimer Disease Cooperative Study Clinical Global Impression of Change (CGIC) score of 1 or 2 or a Neurobehavioral Rating Scale agitation subscale (NBRS-A) score reduction ≥ 50% from baseline. "Stable early response" was defined as meeting the aforementioned criteria at both weeks 3 and 9, "late response" was response at week 9 but not at week 3, and "unstable response" was response at week 3 but not at week 9. In the primary analyses, citalopram was superior to placebo on both the CGIC and the NBRS-A response measures. Little between-group differences were found in response rates in the first 3 weeks of the study (21% versus 19% on the CGIC). Citalopram patients were more likely than placebo patients to be a late responder (18% versus 8% on CGIC, Fisher's exact p = 0.09; 31% versus 15% on NBRS-A, Fisher's exact p = 0.02). Approximately half of citalopram responders (45%-56%) at end of study achieved response later in the study compared with 30%-44% of placebo responders. Treatment with citalopram for agitation in AD needs to be at least 9 weeks in duration to allow sufficient time for full response. Study duration is an important factor to consider in the design of clinical trials for agitation in AD. Copyright © 2015 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

  16. Treatment response, safety, and tolerability of paliperidone extended release treatment in patients recently diagnosed with schizophrenia

    PubMed Central

    Peuskens, Joseph; Vauth, Roland; Sacchetti, Emilio; bij de Weg, Haye; Herken, Hasan; Lahaye, Marjolein; Schreiner, Andreas

    2015-01-01

    Objective: This study was designed to explore the efficacy and tolerability of oral paliperidone extended release (ER) in a sample of patients who were switched to flexible doses within the crucial first 5 years after receiving a diagnosis of schizophrenia. Methods: Patients were recruited from 23 countries. Adults with nonacute but symptomatic schizophrenia, previously unsuccessfully treated with other oral antipsychotics, were transitioned to paliperidone ER (3–12 mg/day) and prospectively treated for up to 6 months. The primary efficacy outcome for patients switching for the main reason of lack of efficacy with their previous antipsychotic was at least 20% improvement in Positive and Negative Syndrome Scale (PANSS) total scores. For patients switching for other main reasons, such as lack of tolerability, compliance or ‘other’, the primary outcome was non-inferiority in efficacy compared with the previous oral antipsychotic. Results: For patients switching for the main reason of lack of efficacy, 63.1% achieved an improvement of at least 20% in PANSS total scores from baseline to endpoint. For each reason for switching other than lack of efficacy, efficacy maintenance after switching to paliperidone ER was confirmed. Statistically significant improvement in patient functioning from baseline to endpoint, as assessed by the Personal and Social Performance scale, was observed (p < 0.0001). Treatment satisfaction with prior antipsychotic treatment at baseline was rated ‘good’ to ‘very good’ by 16.8% of patients, and at endpoint by 66.0% of patients treated with paliperidone ER. Paliperidone ER was generally well tolerated, with frequently reported treatment-emergent adverse events being insomnia, anxiety and somnolence. Conclusions: Flexibly dosed paliperidone ER was associated with clinically relevant symptomatic and functional improvement in recently diagnosed patients with non-acute schizophrenia previously unsuccessfully treated with other oral

  17. Interferon-gamma response to the treatment of active pulmonary and extra-pulmonary tuberculosis.

    PubMed

    Liang, L; Shi, R; Liu, X; Yuan, X; Zheng, S; Zhang, G; Wang, W; Wang, J; England, K; Via, L E; Cai, Y; Goldfeder, L C; Dodd, L E; Barry, C E; Chen, R Y

    2017-10-01

    Interferon-gamma (IFN-γ) release assays (IGRAs) are used to diagnose tuberculosis (TB) but not to measure treatment response. To measure IFN-γ response to active anti-tuberculosis treatment. Patients from the Henan Provincial Chest Hospital, Henan, China, with TB symptoms and/or signs were enrolled into this prospective, observational cohort study and followed for 6 months of treatment, with blood and sputum samples collected at 0, 2, 4, 6, 8, 16 and 24 weeks. The QuantiFERON® TB-Gold assay was run on collected blood samples. Participants received a follow-up telephone call at 24 months to determine relapse status. Of the 152 TB patients enrolled, 135 were eligible for this analysis: 118 pulmonary (PTB) and 17 extra-pulmonary TB (EPTB) patients. IFN-γ levels declined significantly over time among all patients (P = 0.002), with this decline driven by PTB patients (P = 0.001), largely during the initial 8 weeks of treatment (P = 0.019). IFN-γ levels did not change among EPTB patients over time or against baseline culture or drug resistance status. After 6 months of effective anti-tuberculosis treatment, IFN-γ levels decreased significantly in PTB patients, largely over the initial 8 weeks of treatment. IFN-γ concentrations may offer some value for monitoring anti-tuberculosis treatment response among PTB patients.

  18. The Promise of Biological Markers for Treatment Response in First-Episode Psychosis: A Systematic Review

    PubMed Central

    Fond, Guillaume; d’Albis, Marc-Antoine; Jamain, Stéphane; Tamouza, Ryad; Arango, Celso; Fleischhacker, W. Wolfgang; Glenthøj, Birte; Leweke, Markus; Lewis, Shôn; McGuire, Phillip; Meyer-Lindenberg, Andreas; Sommer, Iris E.; Winter-van Rossum, Inge; Kapur, Shitij; Kahn, René S.; Rujescu, Dan; Leboyer, Marion

    2015-01-01

    Successful treatment of first-episode psychosis is one of the major factors that impacts long-term prognosis. Currently, there are no satisfactory biological markers (biomarkers) to predict which patients with a first-episode psychosis will respond to which treatment. In addition, a non-negligible rate of patients does not respond to any treatment or may develop side effects that affect adherence to the treatments as well as negatively impact physical health. Thus, there clearly is a pressing need for defining biomarkers that may be helpful to predict response to treatment and sensitivity to side effects in first-episode psychosis. The present systematic review provides (1) trials that assessed biological markers associated with antipsychotic response or side effects in first-episode psychosis and (2) potential biomarkers associated with biological disturbances that may guide the choice of conventional treatments or the prescription of innovative treatments. Trials including first-episode psychoses are few in number. Most of the available data focused on pharmacogenetics markers with so far only preliminary results. To date, these studies yielded—beside markers for metabolism of antipsychotics—no or only a few biomarkers for response or side effects, none of which have been implemented in daily clinical practice. Other biomarkers exploring immunoinflammatory, oxidative, and hormonal disturbances emerged as biomarkers of first-episode psychoses in the last decades, and some of them have been associated with treatment response. In addition to pharmacogenetics, further efforts should focus on the association of emergent biomarkers with conventional treatments or with innovative therapies efficacy, where some preliminary data suggest promising results. PMID:25759473

  19. Impact of Interleukin 28B Genotype on the Virological Responses in Chronic Hepatitis C Treatment

    PubMed Central

    Aygen, Bilgehan; Yildiz, Orhan; Akhan, Sila; Gunal, Ozgur; Taheri, Serpil; Zararsiz, Gokmen; Sayan, Murat; Rustemoglu, Aydin; Altinok, Elif Sargin

    2014-01-01

    Background Interleukin (IL) 28B single nucleotide polymorphisms may play a role in the clearance of hepatitis C virus (HCV). We aimed to evaluate the treatment response of chronic HCV infection patients to pegile interferon (pegIFN) and ribavirin treatment with regard to IL28B rs12979860 C/T polymorphism. Methods A total of 186 patients (mean age, 55.6 ± 10 years; 65.1% female) who underwent pegIFN and ribavirin treatment for chronic HCV infection were studied. We analyzed demographics, HCV genotype, baseline alanine aminotransferase (ALT) levels, histopathological data, viral load before treatment and at 4, 12, 24, 48, and 72 weeks from the treatment start, and IL28B genotype. IL28B polymorphism was genotyped using polymerase chain reaction based restriction fragment length polymorphism (PCR-RFLP) in all the subjects. Results One hundred forty-five (86.8%) patients were infected with viral genotype 1b, and 13.2% were infected with viral genotype 4. The rates of C/C, C/T, and T/T genotypes were 22.6%, 52.7%, and 24.7% respectively. The percentage of patients with a viral load over 400,000 IU/mL was higher in the C/T group (P = 0.020). Of the patients, 44.6% provided sustained virological response (SVR) to pegIFN and ribavirin combination treatment. The frequency of T allele was 41% in patients with SVR, whereas 59% patients provided no response (P < 0.001). SVR was obtained in 66.7%, 42.9%, and 28.3% of CC, CT, and TT groups (P = 0.001). The rates of rapid virological response (RVR), early virological response (EVR), end-of-treatment response (ETR), and SVR were higher in the CC group than other groups (P = 0.216, P < 0.001, P = 0.001, P = 0.001, respectively). The relapse and null response (NR) rates were higher in TT group and partial response rate (PR) was higher in CT group. Conclusions IL28B rs12979860 C/T gene polymorphism affects the response to antiviral treatment in the patients with chronic HCV genotypes 1b and 4 infections. PMID:27785282

  20. Gender and treatment response in substance-use treatment mandated parolees

    PubMed Central

    Johnson, Jennifer E.; Friedmann, Peter D.; Green, Traci C.; Harrington, Magdalena; Taxman, Faye S.

    2011-01-01

    Well-controlled, randomized studies of correctional interventions examining gender effects are rare. This study examined gender main effects and gender by treatment interactions in a multisite randomized trial (N = 431) comparing a new form of correctional supervision for drug-involved offenders (Collaborative Behavioral Management; CBM) to standard parole. Outcomes included repeated measures of yes/no use of primary drug, alcohol use, and recidivism during 9 months post-release. Generalized estimating equation analyses indicated that despite using harder drugs at baseline, women were less likely than men to use their primary drug and to use alcohol during the follow-up period. No gender-related differences in recidivism were found. Treatment interacted with gender to predict alcohol use, with women in CBM reporting the best alcohol outcomes (only 5% used alcohol during the follow-up period). The clear expectations, positive reinforcement, recognition of successes, fairness, and support present in CBM may be particularly important for women parolees. PMID:21266302

  1. Gender and treatment response in substance use treatment-mandated parolees.

    PubMed

    Johnson, Jennifer E; Friedmann, Peter D; Green, Traci C; Harrington, Magdalena; Taxman, Faye S

    2011-04-01

    Well-controlled, randomized studies of correctional interventions examining gender effects are rare. This study examined gender main effects and gender × treatment interactions in a multisite randomized trial (N = 431) comparing a new form of correctional supervision for drug-involved offenders (collaborative behavioral management [CBM]) to standard parole. Outcomes included repeated measures of yes/no use of primary drug, alcohol use, and recidivism during 9 months postrelease. Generalized estimating equation analyses indicated that despite using harder drugs at baseline, women were less likely than men to use their primary drug and to use alcohol during the follow-up period. No gender-related differences in recidivism were found. Treatment interacted with gender to predict alcohol use, with women in CBM reporting the best alcohol outcomes (only 5% of women used alcohol during the follow-up period). The clear expectations, positive reinforcement, recognition of successes, fairness, and support present in CBM may be particularly important for women parolees. Copyright © 2011 Elsevier Inc. All rights reserved.

  2. Comparative effectiveness of imaging modalities to determine metastatic breast cancer treatment response.

    PubMed

    Lee, Christoph I; Gold, Laura S; Nelson, Heidi D; Chou, Roger; Ramsey, Scott D; Sullivan, Sean D

    2015-02-01

    We performed a systematic review to address the comparative effectiveness of different imaging modalities in evaluating treatment response among metastatic breast cancer patients. We searched seven multidisciplinary electronic databases for relevant publications (January 2003-December 2013) and performed dual abstraction of details and results for all clinical studies that involved stage IV breast cancer patients and evaluated imaging for detecting treatment response. Among 159 citations reviewed, 17 single-institution, non-randomized, observational studies met our inclusion criteria. Several studies demonstrate that changes in PET/CT standard uptake values are associated with changes in tumor volume as determined by bone scan, MRI, and/or CT. However, no studies evaluated comparative test performance between modalities or determined relationships between imaging findings and subsequent clinical decisions. Evidence for imaging's effectiveness in determining treatment response among metastatic breast cancer patients is limited. More rigorous research is needed to address imaging's value in this patient population.

  3. Dissecting the Heterogeneity of Treatment Response in First-Episode Schizophrenia.

    PubMed

    Malhotra, Anil K

    2015-11-01

    The Mental Health Centers for Intervention Development and Applied Research (CIDAR) program prioritized research to provide an evidence base for biomarker development. At the Zucker Hillside Hospital (ZHH), our CIDAR grant supported research on a comprehensive investigation of treatment response and outcome in first episode schizophrenia. Results provide evidence that baseline neuroimaging, neurocognitive, and genetic measures are significantly associated with clinical response to treatment, and that our currently available interventions can effectively treat aspects of psychotic illness, as well as potentially reduce comorbidity associated with illness. Future research may include combining modalities to more robustly predict response and identify treatment targets, as well as to further develop more effective intervention strategies for these devastating and disabling disorders. © The Author 2015. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.

  4. Neural Mechanisms of Improvements in Social Motivation After Pivotal Response Treatment: Two Case Studies

    PubMed Central

    Voos, Avery C.; Pelphrey, Kevin A.; Tirrell, Jonathan; Bolling, Danielle Z.; Vander Wyk, Brent; Kaiser, Martha D.; McPartland, James C.; Volkmar, Fred R.; Ventola, Pamela

    2016-01-01

    Pivotal response treatment (PRT) is an empirically validated behavioral treatment that has widespread positive effects on communication, behavior, and social skills in young children with autism spectrum disorder (ASD). For the first time, functional magnetic resonance imaging was used to identify the neural correlates of successful response to PRT in two young children with ASD. Baseline measures of social communication, adaptive behavior, eye tracking and neural response to social stimuli were taken prior to treatment and after 4 months of PRT. Both children showed striking gains on behavioral measures and also showed increased activation to social stimuli in brain regions utilized by typically developing children. These results suggest that neural systems supporting social perception are malleable through implementation of PRT. PMID:23104615

  5. Smoking cessation and adolescent treatment response with comorbid ADHD☆,☆☆,★

    PubMed Central

    Pagano, Maria E.; Delos-Reyes, Christina M.; Wasilow, Sherry; Svala, Kathleen M.; Kurtz, Steven P.

    2016-01-01

    Minors entering treatment for alcohol and other drug (AOD) use disorders tend to smoke at high rates, and many have comorbid attention deficit hyperactivity disorder (ADHD). Clear-air laws force patients to refrain from smoking on the premises of AOD treatment facilities, which may hinder the progress of treatment-seeking populations who smoke and struggle with ADHD comorbidity in particular. This study explores clinical characteristics associated with smoking among youths presenting for residential treatment, clinical characteristics associated with smoking cessation, and the impact of smoking cessation with ADHD comorbidity on AOD treatment response. Participants were 195 adolescents (52% female, aged 14–18 years) court-referred to residential treatment. Data were collected at intake, prospectively each week for the 10-week treatment period, and at discharge. Two-thirds (67%) of the enrollment sample entered treatment smoking half a pack a day on average, a large proportion (50%) of which did not smoke during treatment. ADHD patients were more likely to smoke before and during treatment except for those who got active in service and step-work. Quitting smoking did not adversely affect AOD outcomes and was associated with better prognosis of lowered AOD cravings for youths with and without ADHD. Smoking cessation during adolescent AOD treatment is recommended with provision of pharmaceutical and/or behavioral modalities that reduce nicotine withdrawal. PMID:27692184

  6. Guided parent-delivered cognitive behavioral therapy for childhood anxiety: Predictors of treatment response.

    PubMed

    Thirlwall, Kerstin; Cooper, Peter; Creswell, Cathy

    2017-01-01

    Guided Parent-delivered Cognitive Behaviour Therapy (GPD-CBT) is a brief, effective treatment for childhood anxiety disorders, however not all children respond favourably. To examine predictors of response to GPD-CBT. Parents of 125 children (7-12 years) with an anxiety disorder received GPD-CBT over 2.6 or 5.3h. Recovery was measured post treatment and six months later. Younger children and those with primary Generalised Anxiety Disorder (GAD) improved more post treatment, but older children and those without primary GAD had better outcomes at six month follow up. Fewer children allocated to 2.6h had recovered post treatment compared to those allocated to the 5.2h intervention, but did not differ significantly six months later. The identification of predictors of short and longer-term treatment outcomes can guide treatment decisions following this low-intensity approach. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  7. Response of Human Prostate Cancer Cells to Mitoxantrone Treatment in Simulated Microgravity Environment

    NASA Astrophysics Data System (ADS)

    Zhang, Ye; Wu, Honglu

    2012-07-01

    RESPONSE OF HUMAN PROSTATE CANCER CELLS TO MITOXANTRONE TREATMENT IN SIMULATED MICROGRAVITY ENVIRONMENT Ye Zhang1,2, Christopher Edwards3, and Honglu Wu1 1 NASA-Johnson Space Center, Houston, TX 2 Wyle Integrated Science and Engineering Group, Houston, TX 3 Oregon State University, Corvallis, OR This study explores the changes in growth of human prostate cancer cells (LNCaP) and their response to the treatment of an antineoplastic agent, mitoxantrone, under the simulated microgravity condition. In comparison to static 1g, microgravity and simulated microgravity have been shown to alter global gene expression patterns and protein levels in various cultured cell models or animals. However, very little is known about the effect of altered gravity on the responses of cells to the treatment of drugs, especially chemotherapy drugs. To test the hypothesis that zero gravity would result in altered regulations of cells in response to antineoplastic agents, we cultured LNCaP cells in either a High Aspect Ratio Vessel (HARV) bioreactor at the rotating condition to model microgravity in space or in the static condition as control, and treated the cells with mitoxantrone. Cell growth, as well as expressions of oxidative stress related genes, were analyzed after the drug treatment. Compared to static 1g controls, the cells cultured in the simulated microgravity environment did not present significant differences in cell viability, growth rate, or cell cycle distribution. However, after mitoxantrone treatment, a significant proportion of bioreactor cultured cells became apoptotic or was arrested in G2. Several oxidative stress related genes also showed a higher expression level post mitoxantrone treatment. Our results indicate that simulated microgravity may alter the response of LNCaP cells to mitoxantrone treatment. Understanding the mechanisms by which cells respond to drugs differently in an altered gravity environment will be useful for the improvement of cancer treatment on

  8. Predicting Treatment Response in Social Anxiety Disorder From Functional Magnetic Resonance Imaging

    PubMed Central

    Doehrmann, Oliver; Ghosh, Satrajit S.; Polli, Frida E.; Reynolds, Gretchen O.; Horn, Franziska; Keshavan, Anisha; Triantafyllou, Christina; Saygin, Zeynep M.; Whitfield-Gabrieli, Susan; Hofmann, Stefan G.; Pollack, Mark; Gabrieli, John D.

    2013-01-01

    Context Current behavioral measures poorly predict treatment outcome in social anxiety disorder (SAD). To our knowledge, this is the first study to examine neuroimaging-based treatment prediction in SAD. Objective To measure brain activation in patients with SAD as a biomarker to predict subsequent response to cognitive behavioral therapy (CBT). Design Functional magnetic resonance imaging (fMRI) data were collected prior to CBT intervention. Changes in clinical status were regressed on brain responses and tested for selectivity for social stimuli. Setting Patients were treated with protocol-based CBT at anxiety disorder programs at Boston University or Massachusetts General Hospital and underwent neuroimaging data collection at Massachusetts Institute of Technology. Patients Thirty-nine medication-free patients meeting DSM-IV criteria for the generalized subtype of SAD. Interventions Brain responses to angry vs neutral faces or emotional vs neutral scenes were examined with fMRI prior to initiation of CBT. Main Outcome Measures Whole-brain regression analyses with differential fMRI responses for angry vs neutral faces and changes in Liebowitz Social Anxiety Scale score as the treatment outcome measure. Results Pretreatment responses significantly predicted subsequent treatment outcome of patients selectively for social stimuli and particularly in regions of higher-order visual cortex. Combining the brain measures with information on clinical severity accounted for more than 40% of the variance in treatment response and substantially exceeded predictions based on clinical measures at baseline. Prediction success was unaffected by testing for potential confounding factors such as depression severity at baseline. Conclusions The results suggest that brain imaging can provide biomarkers that substantially improve predictions for the success of cognitive behavioral interventions and more generally suggest that such biomarkers may offer evidence-based, personalized

  9. Predicting treatment response in social anxiety disorder from functional magnetic resonance imaging.

    PubMed

    Doehrmann, Oliver; Ghosh, Satrajit S; Polli, Frida E; Reynolds, Gretchen O; Horn, Franziska; Keshavan, Anisha; Triantafyllou, Christina; Saygin, Zeynep M; Whitfield-Gabrieli, Susan; Hofmann, Stefan G; Pollack, Mark; Gabrieli, John D

    2013-01-01

    Current behavioral measures poorly predict treatment outcome in social anxiety disorder (SAD). To our knowledge, this is the first study to examine neuroimaging-based treatment prediction in SAD. To measure brain activation in patients with SAD as a biomarker to predict subsequent response to cognitive behavioral therapy (CBT). Functional magnetic resonance imaging (fMRI) data were collected prior to CBT intervention. Changes in clinical status were regressed on brain responses and tested for selectivity for social stimuli. Patients were treated with protocol-based CBT at anxiety disorder programs at Boston University or Massachusetts General Hospital and underwent neuroimaging data collection at Massachusetts Institute of Technology. Thirty-nine medication-free patients meeting DSM-IV criteria for the generalized subtype of SAD. Brain responses to angry vs neutral faces or emotional vs neutral scenes were examined with fMRI prior to initiation of CBT. Whole-brain regression analyses with differential fMRI responses for angry vs neutral faces and changes in Liebowitz Social Anxiety Scale score as the treatment outcome measure. Pretreatment responses significantly predicted subsequent treatment outcome of patients selectively for social stimuli and particularly in regions of higher-order visual cortex. Combining the brain measures with information on clinical severity accounted for more than 40% of the variance in treatment response and substantially exceeded predictions based on clinical measures at baseline. Prediction success was unaffected by testing for potential confounding factors such as depression severity at baseline. The results suggest that brain imaging can provide biomarkers that substantially improve predictions for the success of cognitive behavioral interventions and more generally suggest that such biomarkers may offer evidence-based, personalized medicine approaches for optimally selecting among treatment options for a patient.

  10. Effect of parental age on treatment response in adolescents with schizophrenia.

    PubMed

    Opler, Mark; Malaspina, Dolores; Gopal, Srihari; Nuamah, Isaac; Savitz, Adam J; Singh, Jaskaran; Hough, David

    2013-12-01

    Advanced paternal age (APA) is associated with increased risk for schizophrenia, but its effect on treatment response has not been longitudinally studied. Association of parental ages at the time of the child's birth with age of onset, initial symptom severity and treatment response (to placebo and three different weight-based doses of paliperidone ER) in adolescents with schizophrenia was assessed in a post-hoc analysis using data from a 6-week double-blind study, the primary results of which are published (NCT00518323). The mean (SD) paternal age was 29.2 (6.2) years, range (16-50) and maternal age was 26.8 (5.7) years, range (17-42) at childbirth for the 201 adolescents (ages 12-17 years) included in the analysis. While parental ages were uncorrelated with age of onset or initial symptom severity, both maternal and paternal ages showed significant effects on treatment response (p<0.03) of all paliperidone ER arms versus placebo. Paternal age was significantly correlated to improvement in positive symptoms and maternal age significantly related to negative symptoms, although only paternal age remained significantly associated with the treatment response in analyses that included both parents' ages. APA was associated with greater treatment response to both paliperidone ER and placebo, but not to age of onset or initial symptom severity in adolescents with schizophrenia. The results support the contention that APA-related schizophrenia has distinct underpinnings from other cases. Further studies are required to explore the role of genetic and environmental factors, and their interactions, in treatment response in this complex disorder. © 2013.

  11. Drawing Sound Inferences Concerning the Effects of Treatment on Dispersion in Outcomes: Bringing to Light Individual Differences in Response to Treatment. CSE Technical Report 710

    ERIC Educational Resources Information Center

    Seltzer, Michael; Kim, Jinok

    2007-01-01

    Individual differences in response to a given treatment have been a longstanding interest in education. While many evaluation studies focus on average treatment effects (i.e., the effects of treatments on the levels of outcomes of interest), this paper additionally considers estimating the effects of treatments on the dispersion in outcomes.…

  12. In vivo hyperspectral imaging of microvessel response to trastuzumab treatment in breast cancer xenografts

    PubMed Central

    McCormack, Devin R.; Walsh, Alex J.; Sit, Wesley; Arteaga, Carlos L.; Chen, Jin; Cook, Rebecca S.; Skala, Melissa C.

    2014-01-01

    HER2-amplified (HER2 + ) breast cancers are treated with the anti-HER2 monoclonal antibody trastuzumab. Although trastuzumab reduces production of the angiogenic factor VEGF in HER2 + tumors, the acute and sustained effects of trastuzumab on the tumor vasculature are not understood fully, particularly in trastuzumab-resistant tumors. We used mouse models of trastuzumab sensitive and trastuzumab-resistant HER2 + breast cancers to measure dynamic changes in tumor microvessel density and hemoglobin oxygenation (sO2) in vivo using quantitative hyperspectral imaging at 2, 5, 9, and 14 days after antibody treatment. Further analysis quantified the distribution of microvessels into low and high oxygenation groups, and monitored changes in these distributions with trastuzumab treatment. Gold standard immunohistochemistry was performed to validate complementary markers of tumor cell and vascular response to treatment. Trastuzumab treatment in both responsive and resistant tumors resulted in decreased sO2 5 days after initial treatment when compared to IgG-treated controls (p<0.05). Importantly, responsive tumors showed significantly higher vessel density and significantly lower sO2 than all other groups at 5 days post-treatment (p<0.05). Distribution analysis of vessel sO2 showed a significant (p<0.05) shift of highly oxygenated vessels towards lower oxygenation over the time-course in both trastuzumab-treated responsive and resistant tumors. This study suggests that longitudinal hyperspectral imaging of microvessel sO2 and density could distinguish trastuzumab-responsive from trastuzumab-resistant tumors, a finding that could be exploited in the post-neoadjuvant setting to guide post-surgical treatment decisions. PMID:25071962

  13. Discordant Treatment Responses to Combination Antiretroviral Therapy in Rwanda: A Prospective Cohort Study

    PubMed Central

    Kayigamba, Felix R.; Franke, Molly F.; Bakker, Mirjam I.; Rodriguez, Carly A.; Bagiruwigize, Emmanuel; Wit, Ferdinand WNM; Rich, Michael L.; Schim van der Loeff, Maarten F.

    2016-01-01

    Introduction Some antiretroviral therapy naïve patients starting combination antiretroviral therapy (cART) experience a limited CD4 count rise despite virological suppression, or vice versa. We assessed the prevalence and determinants of discordant treatment responses in a Rwandan cohort. Methods A discordant immunological cART response was defined as an increase of <100 CD4 cells/mm3 at 12 months compared to baseline despite virological suppression (viral load [VL] <40 copies/mL). A discordant virological cART response was defined as detectable VL at 12 months with an increase in CD4 count ≥100 cells/mm3. The prevalence of, and independent predictors for these two types of discordant responses were analysed in two cohorts nested in a 12-month prospective study of cART-naïve HIV patients treated at nine rural health facilities in two regions in Rwanda. Results Among 382 patients with an undetectable VL at 12 months, 112 (29%) had a CD4 rise of <100 cells/mm3. Age ≥35 years and longer travel to the clinic were independent determinants of an immunological discordant response, but sex, baseline CD4 count, body mass index and WHO HIV clinical stage were not. Among 326 patients with a CD4 rise of ≥100 cells/mm3, 56 (17%) had a detectable viral load at 12 months. Male sex was associated with a virological discordant treatment response (P = 0.05), but age, baseline CD4 count, BMI, WHO HIV clinical stage, and travel time to the clinic were not. Conclusions Discordant treatment responses were common in cART-naïve HIV patients in Rwanda. Small CD4 increases could be misinterpreted as a (virological) treatment failure and lead to unnecessary treatment changes. PMID:27438000

  14. Multiparametric Evaluation of Treatment Response to Neoadjuvant Chemotherapy in Breast Cancer Using Integrated PET/MR.

    PubMed

    Wang, Jane; Shih, Tiffany Ting-Fang; Yen, Ruoh-Fang

    2017-07-01

    The aim of this study was to investigate whether integrated PET/MR system can predict the treatment response to neoadjuvant chemotherapy (NAC) early in the course of breast cancer treatment. Fourteen women with newly diagnosed invasive breast cancer (median age, 54.5 years) were recruited. Each participant underwent 2 PET/MR studies. Study 1 was pre-NAC; study 2 was early in NAC treatment (after the first or second cycle). PET parameters included SUVmax and total lesion glycolysis (TLG). MRI parameters included choline signal-to-noise ratio (ChoSNR), peak enhancement ratio (PER), and the minimum apparent diffusion coefficient (ADCmin). The pathologic response was categorized as a pathologic complete response or residual cellularity of less than 10% (group 1) and residual cellularity of 10% or greater (group 2). The accuracy of the NAC response prediction was obtained by receiver operating characteristic analysis. Group 1 showed a greater reduction of SUVmax (percentage change, [INCREMENT]% SUVmax, P = 0.013; area under the receiver operating characteristic curve [AUC], 0.898), TLG ([INCREMENT]%TLG, P = 0.018; AUC = 0.878), and PER ([INCREMENT]% PER, P = 0.035; AUC = 0.837) than did group 2. The ChoSNR, ADCmin, [INCREMENT]%ChoSNR, and [INCREMENT]%ADCmin did not differ significantly between the 2 groups. The hybrid markers, [INCREMENT]%SUVmax/[INCREMENT]%ADCmin (AUC = 0.976) and [INCREMENT]%TLG/[INCREMENT]%ADCmin (AUC = 0.905), showed greater accuracy in predicting NAC response than the individual PET/MR parameters. The PET/MR parameters can predict the NAC response early in the course of breast cancer treatment. The hybrid markers more accurately predicted treatment response than the individual PET/MR parameters.

  15. Responsive cortical stimulation for the treatment of medically intractable partial epilepsy.

    PubMed

    Morrell, Martha J

    2011-09-27

    This multicenter, double-blind, randomized controlled trial assessed the safety and effectiveness of responsive cortical stimulation as an adjunctive therapy for partial onset seizures in adults with medically refractory epilepsy. A total of 191 adults with medically intractable partial epilepsy were implanted with a responsive neurostimulator connected to depth or subdural leads placed at 1 or 2 predetermined seizure foci. The neurostimulator was programmed to detect abnormal electrocorticographic activity. One month after implantation, subjects were randomized 1:1 to receive stimulation in response to detections (treatment) or to receive no stimulation (sham). Efficacy and safety were assessed over a 12-week blinded period and a subsequent 84-week open-label period during which all subjects received responsive stimulation. Seizures were significantly reduced in the treatment (-37.9%, n = 97) compared to the sham group (-17.3%, n = 94; p = 0.012) during the blinded period and there was no difference between the treatment and sham groups in adverse events. During the open-label period, the seizure reduction was sustained in the treatment group and seizures were significantly reduced in the sham group when stimulation began. There were significant improvements in overall quality of life (p < 0.02) and no deterioration in mood or neuropsychological function. Responsive cortical stimulation reduces the frequency of disabling partial seizures, is associated with improvements in quality of life, and is well-tolerated with no mood or cognitive effects. Responsive stimulation may provide another adjunctive treatment option for adults with medically intractable partial seizures. This study provides Class I evidence that responsive cortical stimulation is effective in significantly reducing seizure frequency for 12 weeks in adults who have failed 2 or more antiepileptic medication trials, 3 or more seizures per month, and 1 or 2 seizure foci.

  16. HIV treatment as prevention in Jamaica and Barbados: magic bullet or sustainable response?

    PubMed

    Barrow, Geoffrey; Barrow, Christine

    2015-01-01

    This discursive article introduces HIV treatment as prevention (TasP) and identifies various models for its extrapolation to wider population levels. Drawing on HIV surveillance data for Jamaica and Barbados, the article identifies significant gaps in HIV response programming in relation to testing, antiretroviral treatment coverage, and treatment adherence, thereby highlighting the disparity between assumptions and prerequisites for TasP success. These gaps are attributable, in large part, to sociocultural impediments and structural barriers, severe resource constraints, declining political will, and the redefinition of HIV as a manageable, chronic health issue. Antiretroviral treatment and TasP can realize success only within a combination prevention frame that addresses structural factors, including stigma and discrimination, gender inequality and gender-based violence, social inequality, and poverty. The remedicalization of the response compromises outcomes and undermines the continued potential of HIV programming as an entry point for the promotion of sexual, health, and human rights. © The Author(s) 2013.

  17. Pharmacogenetics and pharmacogenomics for rheumatoid arthritis responsiveness to methotrexate treatment: the 2013 update.

    PubMed

    Zhu, Hong; Deng, Fei-Yan; Mo, Xing-Bo; Qiu, Ying-Hua; Lei, Shu-Feng

    2014-03-01

    Rheumatoid arthritis (RA) is a complex, systemic autoimmune disease characterized by chronic inflammation of multiple peripheral joints, which leads to serious destruction of cartilage and bone, progressive deformity and severe disability. Methotrexate (MTX) is one of the first-line drugs commonly used in RA therapy owing to its excellent long-term efficacy and cheapness. However, the efficacy and toxicity of MTX treatment have significant interpatient variability. Genetic factors contribute to this variability. In this review, we have summarized and updated the progress of RA response to MTX treatment since 2009 by focusing on the fields of pharmacogenetics and pharmacogenomics. Identification of genetic factors involved in MTX treatment response will increase the understanding of RA pathology and the development of new personalized treatments.

  18. Sociotropy and autonomy: relationship to antidepressant drug treatment response and endogenous-nonendogenous dichotomy.

    PubMed

    Peselow, E D; Robins, C J; Sanfilipo, M P; Block, P; Fieve, R R

    1992-08-01

    This study evaluated the relationship of sociotropic and autonomous personality traits with response to pharmacotherapy for 217 depressed outpatients using the Sociotropy-Autonomy Scale. Sociotropy was related to nonendogenous depression, whereas autonomy was related to endogenous depression. Subjects who had high autonomous-low sociotropic traits showed greater response to antidepressants (and greater drug-placebo differences) than those who had high sociotropic-low autonomous traits (who showed no drug-placebo differences). Hierarchical multiple regression analysis showed that the sociotropy-autonomy, but not the endogenous-nonendogenous, distinction was a predictor of drug treatment response. The combination of endogeneity and autonomy predicted response to placebo. If replicated, these findings may enable better matching of patient traits to various treatment modalities for depression.

  19. Interactions between Glucocorticoid Treatment and Cis-Regulatory Polymorphisms Contribute to Cellular Response Phenotypes

    PubMed Central

    Richards, Allison L.; Wen, Xiaoquan; Witonsky, David B.; Baxter, Shaneen; Stephens, Matthew; Di Rienzo, Anna

    2011-01-01

    Glucocorticoids (GCs) mediate physiological responses to environmental stress and are commonly used as pharmaceuticals. GCs act primarily through the GC receptor (GR, a transcription factor). Despite their clear biomedical importance, little is known about the genetic architecture of variation in GC response. Here we provide an initial assessment of variability in the cellular response to GC treatment by profiling gene expression and protein secretion in 114 EBV-transformed B lymphocytes of African and European ancestry. We found that genetic variation affects the response of nearby genes and exhibits distinctive patterns of genotype-treatment interactions, with genotypic effects evident in either only GC-treated or only control-treated conditions. Using a novel statistical framework, we identified interactions that influence the expression of 26 genes known to play central roles in GC-related pathways (e.g. NQO1, AIRE, and SGK1) and that influence the secretion of IL6. PMID:21750684

  20. Success rates and immunologic responses of autogenic, allogenic, and xenogenic treatments to repair articular cartilage defects.

    PubMed

    Revell, Christopher M; Athanasiou, Kyriacos A

    2009-03-01

    This review examines current approaches available for articular cartilage repair, not only in terms of their regeneration potential, but also as a function of immunologic response. Autogenic repair techniques, including osteochondral plug transplantation, chondrocyte implantation, and microfracture, are the most widely accepted clinical treatment options due to the lack of immunogenic reactions, but only moderate graft success rates have been reported. Although suspended allogenic chondrocytes are shown to evoke an immune response upon implantation, allogenic osteochondral plugs and tissue-engineered grafts using allogenic chondrocytes exhibit a tolerable immunogenic response. Additionally, these repair techniques produce neotissue with success rates approaching those of currently available autogenic repair techniques, while simultaneously obviating their major hindrance of donor tissue scarcity. To date, limited research has been performed with xenogenic tissue, although several studies demonstrate the potential for its long-term success. This article focuses on the various treatment options for cartilage repair and their associated success rates and immunologic responses.

  1. Tool Support to Enable Evaluation of the Clinical Response to Treatment

    PubMed Central

    Levy, Mia A.; Rubin, Daniel L.

    2008-01-01

    Objective criteria for measuring response to cancer treatment are critical to clinical research and practice. The National Cancer Institute has developed the Response Evaluation Criteria in Solid Tumors (RECIST)1 method to quantify treatment response. RECIST evaluates response by assessing a set of measurable target lesions in baseline and follow-up radiographic studies. However, applying RECIST consistently is challenging due to inter-observer variability among oncologists and radiologists in choice and measurement of target lesions. We analyzed the radiologist-oncologist workflow to determine whether the information collected is sufficient for reliably applying RECIST. We evaluated radiology reports and image markup (radiologists), and clinical flow sheets (oncologists). We found current reporting of radiology results insufficient for consistent application of RECIST, compared with flow sheets. We identified use cases and functional requirements for an informatics tool that could improve consistency and accuracy in applying methods such as RECIST. PMID:18998923

  2. Success Rates and Immunologic Responses of Autogenic, Allogenic, and Xenogenic Treatments to Repair Articular Cartilage Defects

    PubMed Central

    Revell, Christopher M.

    2009-01-01

    This review examines current approaches available for articular cartilage repair, not only in terms of their regeneration potential, but also as a function of immunologic response. Autogenic repair techniques, including osteochondral plug transplantation, chondrocyte implantation, and microfracture, are the most widely accepted clinical treatment options due to the lack of immunogenic reactions, but only moderate graft success rates have been reported. Although suspended allogenic chondrocytes are shown to evoke an immune response upon implantation, allogenic osteochondral plugs and tissue-engineered grafts using allogenic chondrocytes exhibit a tolerable immunogenic response. Additionally, these repair techniques produce neotissue with success rates approaching those of currently available autogenic repair techniques, while simultaneously obviating their major hindrance of donor tissue scarcity. To date, limited research has been performed with xenogenic tissue, although several studies demonstrate the potential for its long-term success. This article focuses on the various treatment options for cartilage repair and their associated success rates and immunologic responses. PMID:19063664

  3. Interferon gamma release assays for monitoring the response to treatment for tuberculosis: A systematic review.

    PubMed

    Clifford, Vanessa; He, Yu; Zufferey, Christel; Connell, Tom; Curtis, Nigel

    2015-12-01

    The ability to monitor the response to therapy for tuberculosis (TB) and confirm adequate treatment would be a major advance. The utility of interferon gamma assays (IGRA) for this purpose remains uncertain. A systematic search of all studies investigating commercial IGRA to monitor anti-tuberculous treatment was done. Studies were included if they included an IGRA before the start of, and at least once during, treatment for active or latent TB. We identified 30 studies, of which 24 used QuantiFERON-TB (QFT), three used T-SPOT.TB and three used both QFT and T-SPOT.TB. Most studies were done in low TB incidence countries. No uniform pattern was seen in IGRA conversion and reversion rates at the end of treatment for active or latent TB. In most studies, the majority of IGRA results remained positive at the end of treatment. In many studies, the quantitative levels of IFN-γ decreased during treatment, particularly in active TB. There was significant heterogeneity in the included studies. While quantitative IGRA responses generally fall during treatment for TB, the large degree of variation in results between participants in each study means that IGRAs are unlikely to be useful for monitoring anti-tuberculous treatment in clinical practice for any individual patient. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Standardization of terminology of virological response in the treatment of chronic hepatitis C: panel recommendations.

    PubMed

    Jacobson, I M; Poordad, F; Brown, R S; Kwo, P Y; Reddy, K R; Schiff, E

    2012-04-01

    The treatment paradigm for hepatitis C virus (HCV) infection is at a critical point in its evolution. The addition of a protease inhibitor to peginterferon plus ribavirin has become the new standard-of-care treatment for most patients. Data from clinical trials of new antivirals have been difficult to interpret and compare, partly because of heterogeneity in trial design, and partly because of inconsistencies in terminology used to define viral responses and the populations evaluated. Present definitions of viral responses for treatment with peginterferon and ribavirin are insufficient for novel treatment paradigms. Further, categorization of prior patient treatment experience in clinical trials, particularly of nonresponders to prior therapy, is inconsistent. Existing terms and definitions must be updated, standardized and/or redefined for easier interpretation of data and effective communication among clinicians. A panel of experts in HCV infection treatment met on 3 December 2009. Goals of the panel were to evaluate terms and definitions used traditionally in treatment with peginterferon and ribavirin, to refine and clarify definitions of existing terms that have varying meanings and to propose new terms and definitions appropriate for novel treatment paradigms emerging with development of new agents. A number of recommendations were accepted unanimously by the panel. Adoption of these terms would improve communication among investigators, enhance comparability among clinical trials, facilitate development of therapeutic guidelines and provide a standardized terminology for use in clinical practice.

  5. Decreased Total Antioxidant Activity in Major Depressive Disorder Patients Non-Responsive to Antidepressant Treatment

    PubMed Central

    Baek, Song-Eun; Lee, Gyoung-Ja; Rhee, Chang-Kyu; Rho, Dae-Young; Kim, Do-Hoon; Huh, Sun

    2016-01-01

    Objective This study aimed to evaluate the total antioxidant activity (TAA) in patients with major depressive disorder (MDD) and the effect of antidepressants on TAA using a novel potentiometric method. Methods Twenty-eight patients with MDD and thirty-one healthy controls were enrolled in this study. The control group comprised 31 healthy individuals matched for gender, drinking and smoking status. We assessed symptoms of depression using the Hamilton Depression Rating Scale (HAMD) and the Beck Depression Inventory (BDI). We measured TAA using potentiometry. All measurements were made at baseline and four and eight weeks later. Results There was a significant negative correlation between BDI scores and TAA. TAA was significantly lower in the MDD group than in controls. When the MDD group was subdivided into those who showed clinical response to antidepressant therapy (response group) and those who did not (non-response group), only the non-response group showed lower TAA, while the response group showed no significant difference to controls at baseline. After eight weeks of antidepressant treatment, TAA in both the response and non-response groups was similar, and there was no significant difference among the three groups. Conclusion These results suggest that the response to antidepressant treatment in MDD patients might be predicted by measuring TAA. PMID:27081384

  6. Predicting milk-production responses after an autumn treatment of pastured dairy herds with eprinomectin.

    PubMed

    Charlier, Johannes; Duchateau, Luc; Claerebout, Edwin; Vercruysse, Jozef

    2007-02-28

    The objectives of this study were (1) to determine the effect of a treatment with eprinomectin in autumn of pastured dairy herds on the anti-Ostertagia ostertagi bulk-tank milk antibody level, (2) to determine the overall effect of this treatment on three milk-production parameters (milk yield, protein % and fat %) and (3) to investigate the value of the pre-treatment Ostertagia-specific bulk-tank milk antibody level to predict the production response after anthelmintic treatment. One hundred and nineteen herds in Flanders (Belgium) were randomly assigned to a treatment with eprinomectin or a placebo in October 2004. Bulk-tank milk samples were collected monthly from August 2004 until April 2005, and the antibody levels against O. ostertagi were determined as optical density ratios (ODRs) with an ELISA. The treatment effect over the 4 months following treatment on three production parameters (milk yield, milk-protein %, milk-fat %) was estimated by mixed models with herd as a random effect. The treatment effect on milk yield was also investigated within six categories of the pre-treatment ODR. The ODR values were lower in the eprinomectin group than in the control group at each time point after treatment. The overall effect on milk yield was estimated at 1.2 kg/cow/day, whereas no effect on the milk-protein % and milk-fat % was observed. Herds in the highest pre-treatment ODR category (>0.84) had a positive milk-yield response of 4.0 kg/cow/day (95%-confidence interval: 1.0; 7.0), while the 95%-confidence intervals of the milk-yield responses in the other categories all included zero. This study demonstrates that treatment with eprinomectin of pastured dairy cows in autumn will lower the Ostertagia-specific bulk-tank milk antibody level during the stabling period and can result in a consistent increase in milk yield. The results indicate that an O. ostertagi bulk-tank milk ELISA can be used to identify the herds where the greatest milk-yield response after an

  7. An imaging-based tumour growth and treatment response model: Investigating the effect of tumour oxygenation on radiation therapy response

    PubMed Central

    Jeraj, Robert

    2010-01-01

    A multiscale tumour simulation model employing cell-line-specific biological parameters and functional information derived from pre-therapy PET/CT imaging data was developed to investigate effects of different oxygenation levels on the response to radiation therapy. For each tumour voxel, stochastic simulations were performed to model cellular growth and therapeutic response. Model parameters were fitted to published preclinical experiments of head and neck squamous cell carcinoma (HNSCC). Using the obtained parameters, the model was applied to a human HNSCC case to investigate effects of different uniform and non-uniform oxygenation levels and results were compared for treatment efficacy. Simulations of the preclinical studies showed excellent agreement with published data and underlined the model’s ability to quantitatively reproduce tumour behaviour within experimental uncertainties. When using a simplified transformation to derive non-uniform oxygenation levels from molecular imaging data, simulations of the clinical case showed heterogeneous tumour response and variability in radioresistance with decreasing oxygen levels. Once clinically validated, this model could be used to transform patient-specific data into voxel-based biological objectives for treatment planning and to investigate biologically optimized dose prescriptions. PMID:18677042

  8. Clinical and Radiologic Responses to Cladribine for the Treatment of Erdheim-Chester Disease.

    PubMed

    Goyal, Gaurav; Shah, Mithun V; Call, Timothy G; Litzow, Mark R; Hogan, William J; Go, Ronald S

    2017-09-01

    While cladribine is best known for the treatment of hairy cell leukemia and other lymphoid cancers, it also has activity against myeloid neoplasms, such as Erdheim-Chester disease (ECD). To assess the efficacy of cladribine (2-chloro-2'-deoxyadenosine) in the treatment of ECD. This study was a single-institution retrospective medical record review from January 1, 1998, to April 6, 2016, at a tertiary academic medical center. In all eligible cases, the diagnosis of ECD was made using clinical criteria in conjunction with histopathologic findings. Cladribine therapy in first-line treatment or later. Two response criteria were used, clinical and radiological. For clinical response, the following criteria were used: complete response (complete resolution of symptoms attributed to ECD), partial response (partial resolution of symptoms attributed to ECD), stable disease (no change in symptoms attributed to ECD), and progressive disease (worsening of symptoms attributed to ECD). For radiological response, the following categories were used: complete response (complete resolution of proven or suspected lesion due to ECD), partial response (partial resolution of proven or suspected lesion due to ECD), stable disease (no significant change in proven or suspected lesion due to ECD for ≥3 months), and progressive disease (progression or worsening of proven or suspected lesion due to ECD). A total of 63 adult patients with confirmed ECD were identified. Their median age at diagnosis of ECD was 54 years (age range, 18-80 years), and 67% (42 of 63) were male. Cladribine was the most commonly used chemotherapeutic agent and was administered in 21 of 63 patients (33%). Their median age at the time of cladribine therapy was 62 years (age range, 40-78 years). Cladribine was used as the first-line treatment in 9 patients and as later-line treatment in the remaining 12 patients. The median number of cycles of cladribine administered was 2.5 (range, 1-6). The overall clinical response

  9. Varying responses of insect herbivores to altered plant chemistry under organic and conventional treatments

    PubMed Central

    Staley, Joanna T.; Stewart-Jones, Alex; Pope, Tom W.; Wright, Denis J.; Leather, Simon R.; Hadley, Paul; Rossiter, John T.; van Emden, Helmut F.; Poppy, Guy M.

    2010-01-01

    The hypothesis that plants supplied with organic fertilizers are better defended against insect herbivores than those supplied with synthetic fertilizers was tested over two field seasons. Organic and synthetic fertilizer treatments at two nitrogen concentrations were supplied to Brassica plants, and their effects on the abundance of herbivore species and plant chemistry were assessed. The organic treatments also differed in fertilizer type: a green manure was used for the low-nitrogen treatment, while the high-nitrogen treatment contained green and animal manures. Two aphid species showed different responses to fertilizers: the Brassica specialist Brevicoryne brassicae was more abundant on organically fertilized plants, while the generalist Myzus persicae had higher populations on synthetically fertilized plants. The diamondback moth Plutella xylostella (a crucifer specialist) was more abundant on synthetically fertilized plants and preferred to oviposit on these plants. Glucosinolate concentrations were up to three times greater on plants grown in the organic treatments, while foliar nitrogen was maximized on plants under the higher of the synthetic fertilizer treatments. The varying response of herbivore species to these strong differences in plant chemistry demonstrates that hypotheses on defence in organically grown crops have over-simplified the response of phytophagous insects. PMID:19906673

  10. [Treatment outcome using prednisone in corticosteroid-responsive primary nephrotic syndrome in children].

    PubMed

    Brumariu, O; Cucer, Florentina; Munteanu, Mihaela; Haliţchi, Codruţa; Müller, R; Russu, R

    2005-01-01

    In children, the nephrotic syndrome is usually corticoid-responsive; approximately 70% of patients experience relapses, frequently triggered by infections. Our paper presents the results obtained using a 4 month prednisone regimen. This retrospective study included 83 children afflicted with nephrotic syndrome over a 10 year span. We analyzed: age at diagnosis, boys/girls ratio, response to corticoid treatment - after one month of prednisone and at the completion of the treatment course, number of relapses and their frequency, complications of prednisone treatment. The median age at diagnosis was 4.8 years, males predominating M:F = 1.5:1. Complete response after 4 weeks of prednisone therapy was noted in 98.79% of cases. We had 116 episodes of relapses during the first year of follow-up, occurring in 67.4% of children (27.9% were frequent relapsers, 11.62% subsequently became corticoid-dependent). Late relapses, after the first year, occurred in 32.55% of cases. We noted mostly mild adverse effects of the prednisone treatment: occurrence of infections during therapy (16.27%), cushingoid facies (37.2%), hirsutism (4.6%), high blood pressure (4.65%), stretch marks (2.32%). In conclusion, the 4 month prednisone treatment regimen is efficient in inducing and maintaining a remission. The incidence of relapses is 32.55%, comparable to the figure cited in larger studies. Serious adverse effects are significantly lower with this regimen compared to other corticoid treatment schemes. Key wo

  11. Varying responses of insect herbivores to altered plant chemistry under organic and conventional treatments.

    PubMed

    Staley, Joanna T; Stewart-Jones, Alex; Pope, Tom W; Wright, Denis J; Leather, Simon R; Hadley, Paul; Rossiter, John T; van Emden, Helmut F; Poppy, Guy M

    2010-03-07

    The hypothesis that plants supplied with organic fertilizers are better defended against insect herbivores than those supplied with synthetic fertilizers was tested over two field seasons. Organic and synthetic fertilizer treatments at two nitrogen concentrations were supplied to Brassica plants, and their effects on the abundance of herbivore species and plant chemistry were assessed. The organic treatments also differed in fertilizer type: a green manure was used for the low-nitrogen treatment, while the high-nitrogen treatment contained green and animal manures. Two aphid species showed different responses to fertilizers: the Brassica specialist Brevicoryne brassicae was more abundant on organically fertilized plants, while the generalist Myzus persicae had higher populations on synthetically fertilized plants. The diamondback moth Plutella xylostella (a crucifer specialist) was more abundant on synthetically fertilized plants and preferred to oviposit on these plants. Glucosinolate concentrations were up to three times greater on plants grown in the organic treatments, while foliar nitrogen was maximized on plants under the higher of the synthetic fertilizer treatments. The varying response of herbivore species to these strong differences in plant chemistry demonstrates that hypotheses on defence in organically grown crops have over-simplified the response of phytophagous insects.

  12. Neurofilament light antibodies in serum reflect response to natalizumab treatment in multiple sclerosis.

    PubMed

    Amor, Sandra; van der Star, Baukje J; Bosca, Isabel; Raffel, Joel; Gnanapavan, Sharmilee; Watchorn, Jonathan; Kuhle, Jens; Giovannoni, Gavin; Baker, David; Malaspina, Andrea; Puentes, Fabiola

    2014-09-01

    Increased levels of antibodies to neurofilament light protein (NF-L) in biological fluids have been found to reflect neuroinflammatory responses and neurodegeneration in multiple sclerosis (MS). To evaluate whether levels of serum antibodies against NF-L correlate with clinical variants and treatment response in MS. The autoantibody reactivity to NF-L protein was tested in serum samples from patients with relapsing-remitting MS (RRMS) (n=22) and secondary progressive MS (SPMS) (n=26). Two other cohorts of RRMS patients under treatment with natalizumab were analysed cross-sectionally (n=16) and longitudinally (n=24). The follow-up samples were taken at 6, 12, 18 and 24 months after treatment, and the NF-L antibody levels were compared against baseline levels. NF-L antibodies were higher in MS clinical groups than healthy controls and in RRMS compared to SPMS patients (p<0.001). NF-L antibody levels were lower in natalizumab treated than in untreated patients (p<0.001). In the longitudinal series, NF-L antibody levels decreased over time and a significant difference was found following 24 months of treatment compared with baseline measurements (p=0.001). Drug efficacy in MS treatment indicates the potential use of monitoring the content of antibodies against the NF-L chain as a predictive biomarker of treatment response in MS. © The Author(s) 2014.

  13. The Association between Symptoms and Microbiologically Defined Response to Tuberculosis Treatment

    PubMed Central

    Hales, Craig M.; Heilig, Charles M.; Chaisson, Richard; Leung, Chi Chiu; Chang, Kwok Chiu; Goldberg, Stefan V.; Gordin, Fred; Johnson, John L.; Muzanyi, Grace; Saukkonen, Jussi; Vernon, Andrew; Villarino, M. Elsa; Burman, William J.

    2017-01-01

    Rationale The lack of consistent associations between clinical outcomes and microbiological responses to therapy for some infectious diseases has raised questions about the adequacy of microbiological endpoints for tuberculosis treatment trials. Objectives To evaluate the association between symptoms and microbiological response to tuberculosis treatment. Methods We performed a retrospective analysis of four clinical trials in which participants had culture-positive tuberculosis, standardized symptom assessment, and follow-up mycobacterial cultures. Two trials (studies 22 and 23) followed participants to identify recurrent tuberculosis; participants in studies 27 and 28 were only followed to treatment completion. Measurements and Main Results This analysis included 1,978 participants; 39 (2.0%) had culture-confirmed treatment failure, and 75 (3.9%) had culture-confirmed recurrence. Productive cough was associated with indices of increased mycobacterial burden at diagnosis (acid-fast smear grade, severity of radiographic abnormalities). Fever and sweats improved rapidly with treatment, whereas productive cough decreased more slowly and was present in 20% of visits after treatment completion. During treatment, study participants with productive cough more often had concurrent culture positivity compared with those without productive cough (studies 22 and 23: adjusted odds ratio, 1.80; 95% confidence interval [CI], 1.33–2.44). Finally, symptoms during the latter part of treatment and follow-up were associated with culture-confirmed treatment failure and recurrence in studies 22 and 23 (for cough: adjusted hazard ratio, 2.07; 95% CI, 1.23–3.49; for fever: adjusted hazard ratio, 5.05; 95% CI, 2.76–9.19). Conclusions There are consistent relationships between symptoms and microbiological indices of tuberculosis, including measures of mycobacterial burden at baseline, culture positivity during treatment, and time to culture-confirmed treatment failure and recurrence

  14. The association between symptoms and microbiologically defined response to tuberculosis treatment.

    PubMed

    Hales, Craig M; Heilig, Charles M; Chaisson, Richard; Leung, Chi Chiu; Chang, Kwok Chiu; Goldberg, Stefan V; Gordin, Fred; Johnson, John L; Muzanyi, Grace; Saukkonen, Jussi; Vernon, Andrew; Villarino, M Elsa; Burman, William J

    2013-02-01

    The lack of consistent associations between clinical outcomes and microbiological responses to therapy for some infectious diseases has raised questions about the adequacy of microbiological endpoints for tuberculosis treatment trials. To evaluate the association between symptoms and microbiological response to tuberculosis treatment. We performed a retrospective analysis of four clinical trials in which participants had culture-positive tuberculosis, standardized symptom assessment, and follow-up mycobacterial cultures. Two trials (studies 22 and 23) followed participants to identify recurrent tuberculosis; participants in studies 27 and 28 were only followed to treatment completion. This analysis included 1,978 participants; 39 (2.0%) had culture-confirmed treatment failure, and 75 (3.9%) had culture-confirmed recurrence. Productive cough was associated with indices of increased mycobacterial burden at diagnosis (acid-fast smear grade, severity of radiographic abnormalities). Fever and sweats improved rapidly with treatment, whereas productive cough decreased more slowly and was present in 20% of visits after treatment completion. During treatment, study participants with productive cough more often had concurrent culture positivity compared with those without productive cough (studies 22 and 23: adjusted odds ratio, 1.80; 95% confidence interval [CI], 1.33-2.44). Finally, symptoms during the latter part of treatment and follow-up were associated with culture-confirmed treatment failure and recurrence in studies 22 and 23 (for cough: adjusted hazard ratio, 2.07; 95% CI, 1.23-3.49; for fever: adjusted hazard ratio, 5.05; 95% CI, 2.76-9.19). There are consistent relationships between symptoms and microbiological indices of tuberculosis, including measures of mycobacterial burden at baseline, culture positivity during treatment, and time to culture-confirmed treatment failure and recurrence.

  15. Association between bevacizumab-related hypertension and response to treatment in patients with metastatic colorectal cancer

    PubMed Central

    Dionísio de Sousa, Isabel José; Ferreira, Joana; Rodrigues, Joana; Bonito, Nuno; Jacinto, Paula; Marques, Mariela; Ribeiro, João; Pais, Ana; Gervásio, Helena

    2016-01-01

    Background Bevacizumab has become standard of care as first-line treatment of metastatic colorectal cancer (mCRC), after proving increased response rates and improvement in survival outcomes. Hypertension (HTN) is a common complication of the treatment with bevacizumab and, owing to its close relation with antiangiogenic mechanism, may represent a clinical biomarker to predict the efficacy of the treatment. The aim of this study was to retrospectively evaluate if HTN grades 2 to 3 were correlated with response to treatment with bevacizumab in first line, as well as with improved progression-free survival (PFS) and overall survival (OS), in a series of patients with mCRC. Methods Retrospective evaluation of clinical records of patients with histologically proven mCRC, treated with bevacizumab as first-line treatment, between January 2008 and December 2013. Results 79 patients were evaluated. 51.9% of patients developed HTN G2-G3 during chemotherapy-bevacizumab treatment. In the group of patients who developed bevacizumab-related HTN, 73.2% showed response to treatment (complete response (CR)+ partial response (PR)) and 97.6% achieved disease control (CR, PR or stable disease) compared to 18.4% of patients with response and 63.2% with disease control in the group that did not (OR 12.08; 95% CI 4.13 to 35.29; p<0.001 responders vs non-responders; OR 20.8; 95% CI 2.56 to 168.91; p 0.005 controlled vs non controlled disease). The median OS was 28 months (22.7–33.3). Significant statistical difference was obtained in PFS between the two groups (p<0.001). In the group that developed bevacizumab-related HTN, the median OS was 33 months (25.7–40.3), and in the group that did not, it was 21 months (16.5–25.5) with no significant statistical difference between the two groups (p 0.114). Conclusions In this subset of patients, HTN G2-3 was predictive of response to treatment with bevacizumab and of PFS but not of OS. PMID:27843607

  16. Systematic review: genetic biomarkers associated with anti-TNF treatment response in inflammatory bowel diseases.

    PubMed

    Bek, S; Nielsen, J V; Bojesen, A B; Franke, A; Bank, S; Vogel, U; Andersen, V

    2016-09-01

    Personalised medicine, including biomarkers for treatment selection, may provide new algorithms for more effective treatment of patients. Genetic variation may impact drug response and genetic markers could help selecting the best treatment strategy for the individual patient. To identify polymorphisms and candidate genes from the literature that are associated with anti-tumour necrosis factor (TNF) treatment response in patients with inflammatory bowel diseases (IBD), Crohn's disease (CD) and ulcerative colitis. We performed a PubMed literature search and retrieved studies reporting original data on association between polymorphisms and anti-TNF treatment response and conducted a meta-analysis. A functional polymorphism in FCGR3A was significantly associated with anti-TNF treatment response among CD patients using biological response criterion (decrease in C-reactive protein, levels). Meta-analyses showed that polymorphisms in TLR2 (rs3804099, OR (95% CI) = 2.17 (1.35-3.47)], rs11938228 [OR = 0.64 (0.43-0.96)], TLR4 (rs5030728) [OR = 3.18 (1.63-6.21)], TLR9 (rs352139) [OR = 0.43 (0.21-0.88)], TNFRSF1A (rs4149570) [OR = 2.06 (1.02-4.17)], IFNG (rs2430561) [OR = 1.66 (1.05-2.63)], IL6 (rs10499563) [OR = 1.65 (1.04-2.63)] and IL1B (rs4848306) [OR = 1.88 (1.05-3.35)] were significantly associated with response among IBD patients using clinical response criteria. A positive predictive value of 0.96 was achieved by combining five genetic markers in an explorative analysis. There are no genetic markers currently available which are adequately predictive of anti-TNF response for use in the clinic. Genetic markers bear the advantage that they do not change over time. Therefore, hypothesis-free approaches, testing a large number of polymorphisms in large, well-characterised cohorts, are required in order to identify genetic profiles with larger effect sizes, which could be employed as biomarkers for treatment selection in clinical settings. © 2016 The Authors. Alimentary

  17. Impact of the Definition of Peak Standardized Uptake Value on Quantification of Treatment Response

    PubMed Central

    Vanderhoek, Matt; Perlman, Scott B.; Jeraj, Robert

    2012-01-01

    PET-based treatment response assessment typically measures the change in maximum standardized uptake value (SUVmax), which is adversely affected by noise. Peak SUV (SUVpeak) has been recommended as a more robust alternative, but its associated region of interest (ROIpeak) is not uniquely defined. We investigated the impact of different ROIpeak definitions on quantification of SUVpeak and tumor response. Methods Seventeen patients with solid malignancies were treated with a multitargeted receptor tyrosine kinase inhibitor resulting in a variety of responses. Using the cellular proliferation marker 3′-deoxy-3′-18F-fluorothymidine (18F-FLT), whole-body PET/CT scans were acquired at baseline and during treatment. 18F-FLT–avid lesions (~2/patient) were segmented on PET images, and tumor response was assessed via the relative change in SUVpeak. For each tumor, 24 different SUVpeaks were determined by changing ROIpeak shape (circles vs. spheres), size (7.5–20 mm), and location (centered on SUVmax vs. placed in highest-uptake region), encompassing different definitions from the literature. Within each tumor, variations in the 24 SUVpeaks and tumor responses were measured using coefficient of variation (CV), standardized deviation (SD), and range. For each ROIpeak definition, a population average SUVpeak and tumor response were determined over all tumors. Results A substantial variation in both SUVpeak and tumor response resulted from changing the ROIpeak definition. The variable ROIpeak definition led to an intratumor SUVpeak variation ranging from 49% above to 46% below the mean (CV, 17%) and an intratumor SUVpeak response variation ranging from 49% above to 35% below the mean (SD, 9%). The variable ROIpeak definition led to a population average SUVpeak variation ranging from 24% above to 28% below the mean (CV, 14%) and a population average SUVpeak response variation ranging from only 3% above to 3% below the mean (SD, 2%). The size of ROIpeak caused more

  18. Impact of the definition of peak standardized uptake value on quantification of treatment response.

    PubMed

    Vanderhoek, Matt; Perlman, Scott B; Jeraj, Robert

    2012-01-01

    PET-based treatment response assessment typically measures the change in maximum standardized uptake value (SUV(max)), which is adversely affected by noise. Peak SUV (SUV(peak)) has been recommended as a more robust alternative, but its associated region of interest (ROI(peak)) is not uniquely defined. We investigated the impact of different ROI(peak) definitions on quantification of SUV(peak) and tumor response. Seventeen patients with solid malignancies were treated with a multitargeted receptor tyrosine kinase inhibitor resulting in a variety of responses. Using the cellular proliferation marker 3'-deoxy-3'-(18)F-fluorothymidine ((18)F-FLT), whole-body PET/CT scans were acquired at baseline and during treatment. (18)F-FLT-avid lesions (∼2/patient) were segmented on PET images, and tumor response was assessed via the relative change in SUV(peak). For each tumor, 24 different SUV(peaks) were determined by changing ROI(peak) shape (circles vs. spheres), size (7.5-20 mm), and location (centered on SUV(max) vs. placed in highest-uptake region), encompassing different definitions from the literature. Within each tumor, variations in the 24 SUV(peaks) and tumor responses were measured using coefficient of variation (CV), standardized deviation (SD), and range. For each ROI(peak) definition, a population average SUV(peak) and tumor response were determined over all tumors. A substantial variation in both SUV(peak) and tumor response resulted from changing the ROI(peak) definition. The variable ROI(peak) definition led to an intratumor SUV(peak) variation ranging from 49% above to 46% below the mean (CV, 17%) and an intratumor SUV(peak) response variation ranging from 49% above to 35% below the mean (SD, 9%). The variable ROI(peak) definition led to a population average SUV(peak) variation ranging from 24% above to 28% below the mean (CV, 14%) and a population average SUV(peak) response variation ranging from only 3% above to 3% below the mean (SD, 2%). The size of ROI

  19. Hemisphere Asymmetry of Response to Pharmacologic Treatment in an Alzheimer’s Disease Mouse Model

    PubMed Central

    Manousopoulou, Antigoni; Saito, Satoshi; Yamamoto, Yumi; Al-Daghri, Nasser M.; Ihara, Masafumi; Carare, Roxana O.; Garbis, Spiros D.

    2016-01-01

    The aim of this study was to examine hemisphere asymmetry of response to pharmacologic treatment in an Alzheimer’s disease mouse model using cilostazol as a chemical stimulus. Eight-month-old mice were assigned to vehicle or cilostazol treatment for three months and hemispheres were analyzed using quantitative proteomics. Bioinformatics interpretation showed that following treatment, aggregation of blood platelets significantly decreased in the right hemisphere whereas neurodegeneration significantly decreased and synaptic transmission increased in the left hemisphere only. Our study provides novel evidence on cerebral laterality of pharmacologic activity, with important implications in deciphering regional pharmacodynamic effects of existing drugs thus uncovering novel hemisphere-specific therapeutic targets. PMID:26836196

  20. Early changes in emotional processing as a marker of clinical response to SSRI treatment in depression.

    PubMed

    Godlewska, B R; Browning, M; Norbury, R; Cowen, P J; Harmer, C J

    2016-11-22

    Antidepressant treatment reduces behavioural and neural markers of negative emotional bias early in treatment and has been proposed as a mechanism of antidepressant drug action. Here, we provide a critical test of this hypothesis by assessing whether neural markers of early emotional processing changes predict later clinical response in depression. Thirty-five unmedicated patients with major depression took the selective serotonin re-uptake inhibitor (SSRI), escitalopram (10 mg), over 6 weeks, and were classified as responders (22 patients) versus non-responders (13 patients), based on at least a 50% reduction in symptoms by the end of treatment. The neural response to fearful and happy emotional facial expressions was assessed before and after 7 days of treatment using functional magnetic resonance imaging. Changes in the neural response to these facial cues after 7 days of escitalopram were compared in patients as a function of later clinical response. A sample of healthy controls was also assessed. At baseline, depressed patients showed greater activation to fear versus happy faces than controls in the insula and dorsal anterior cingulate. Depressed patients who went on to respond to the SSRI had a greater reduction in neural activity to fearful versus happy facial expressions after just 7 days of escitalopram across a network of regions including the anterior cingulate, insula, amygdala and thalamus. Mediation analysis confirmed that the direct effect of neural change on symptom response was not mediated by initial changes in depressive symptoms. These results support the hypothesis that early changes in emotional processing with antidepressant treatment are the basis of later clinical improvement. As such, early correction of negative bias may be a key mechanism of antidepressant drug action and a potentially useful predictor of therapeutic response.

  1. Early changes in emotional processing as a marker of clinical response to SSRI treatment in depression

    PubMed Central

    Godlewska, B R; Browning, M; Norbury, R; Cowen, P J; Harmer, C J

    2016-01-01

    Antidepressant treatment reduces behavioural and neural markers of negative emotional bias early in treatment and has been proposed as a mechanism of antidepressant drug action. Here, we provide a critical test of this hypothesis by assessing whether neural markers of early emotional processing changes predict later clinical response in depression. Thirty-five unmedicated patients with major depression took the selective serotonin re-uptake inhibitor (SSRI), escitalopram (10 mg), over 6 weeks, and were classified as responders (22 patients) versus non-responders (13 patients), based on at least a 50% reduction in symptoms by the end of treatment. The neural response to fearful and happy emotional facial expressions was assessed before and after 7 days of treatment using functional magnetic resonance imaging. Changes in the neural response to these facial cues after 7 days of escitalopram were compared in patients as a function of later clinical response. A sample of healthy controls was also assessed. At baseline, depressed patients showed greater activation to fear versus happy faces than controls in the insula and dorsal anterior cingulate. Depressed patients who went on to respond to the SSRI had a greater reduction in neural activity to fearful versus happy facial expressions after just 7 days of escitalopram across a network of regions including the anterior cingulate, insula, amygdala and thalamus. Mediation analysis confirmed that the direct effect of neural change on symptom response was not mediated by initial changes in depressive symptoms. These results support the hypothesis that early changes in emotional processing with antidepressant treatment are the basis of later clinical improvement. As such, early correction of negative bias may be a key mechanism of antidepressant drug action and a potentially useful predictor of therapeutic response. PMID:27874847

  2. Reirradiation on recurrent cervical cancer case: Treatment response and side effects

    NASA Astrophysics Data System (ADS)

    Siregar, M. F.; Supriana, N.; Nuranna, L.; Prihartono, J.

    2017-08-01

    Management of recurrent cervical cancer by reirradiation after radiation treatment remains controversial. In Indonesia, there is currently no data about reirradiation tumor response and side effects. This study aims to assess the tumor response to and side effects of reirradiation, the effect of time interval between first radiation treatment and cancer recurrence on the tumor response and side effects, and the effect of tumor size on tumor response. A cohort retrospective study with no comparison was done with the Radiotherapy Department at Cipto Mangunkusumo General Hospital, Jakarta. Participants were recurrent cervical cancer patients undergoing reirradiation. Data was collected from patients’ medical records and follow-up phone calls. Twenty-two patients participated in this study. Nine patients (40.9%) had complete responses, 10 patients (45.5%) had partial responses, 1 patient (4.5%) had a stable response, and 2 patients (9.1%) had tumor progressions. In general, 15 patients (68.2%) had no to light side effects (grade 0-2 RTOG) and 7 patients (31.8%) had severe side effects (grade 3-4 RTOG). Four patients (18.1%) had severe gastrointestinal acute side effects, 6 patients (27.3%) had severe gastrointestinal late side effects, 2 patients (9.1%) had severe urogenital side effects, and there were no patients had severe urogenital late side effects. There was no significant difference in tumor response between patients with time interval between first radiation treatment and recurrence of <12 months vs. ≥12 months. There was no significant difference in tumor response between patients with tumor size ≤4 cm vs. >4 cm. Reirradiation can be considered as a modality in recurrent cervical cancer management since good tumor response was achieved and the majority of patients had no to light side effects (grade 0-2 RTOG). This study found no correlation between tumor response, side effects, and time gap between first radiation treatment and recurrence of <12 months

  3. A Response Adaptive Randomization Platform Trial for Efficient Evaluation of Ebola Virus Treatments: A Model for Pandemic Response

    PubMed Central

    Berry, Scott M.; Petzold, Elizabeth A.; Dull, Peter; Thielman, Nathan M.; Cunningham, Coleen K.; Corey, G. Ralph; McClain, Micah T.; Hoover, David L.; Russell, James; Griffiss, J. McLeod; Woods, Christopher W.

    2017-01-01

    The outbreak of Ebola Virus Disease (EVD) in West Africa is the largest ever recorded. Numerous treatment alternatives for EVD have been considered, including widely available re-purposed drugs, but initiation of enrollment into clinical trials has been limited. The proposed trial is an adaptive platform design. Multiple agents and combinations will be investigated simultaneously. Additionally, new agents may enter the trial as they become available, and failing agents may be removed. In order to accommodate the many possible agents and combinations, a critical feature of this design is the use of response adaptive randomization to assign treatment regimens. As the trial progresses, the randomization ratio evolves to favor the arms that are performing better, making the design also suitable for all-cause pandemic preparedness planning. The study was approved by US and Sierra Leone ethics committees, and reviewed by the US FDA. Additionally, data management, drug supply lines, and local sites were prepared. However, in response to the declining epidemic seen in February 2015, the trial was not initiated. Sierra Leone remains ready to rapidly activate the protocol as an emergency response trial in the event of a resurgence of EVD. (ClinicalTrials.gov Identifier: NCT02380625) In summary, we have designed a single controlled trial capable of efficiently identifying highly effective or failing regimens among a rapidly evolving list of proposed therapeutic alternatives for EVD and to treat the patients within the trial effectively based on accruing data. Provision of these regimens, if found safe and effective, would have a major impact on future epidemics by providing effective treatment options. PMID:26768569

  4. Concordance between patient and clinician assessment of dry eye severity and treatment response in Taiwan.

    PubMed

    Yeh, Po-Ting; Chien, Hsu-Chih; Ng, Kwong; Tseng, Sung-Huei; Chen, Wei-Li; Hou, Yu-Chih; Wang, I-Jong; Chu, Hsiao-Sung; Kao Yang, Yea-Huei; Hu, Fung-Rong

    2015-05-01

    Accurate diagnosis and early recognition of dry eye symptoms are important in the management of dry eye disease (DED). This study aimed to evaluate concordance between patient and clinician assessment of DED severity and treatment response. This cross-sectional study was conducted in 2 ophthalmology clinics in Taiwan. Clinicians assessed severity based on the Dry Eye Workshop severity grading (levels 1-4; where 4 = most severe), whereas patients completed the Ocular Surface Disease Index questionnaire. To evaluate the treatment response, patients completed the Subject Global Assessment scale, and clinicians independently assessed patients using the Clinical Global Impression scale. A total of 466 patients were included. Clinicians graded 88.3% of patients as level 1/2, 9.0% as level 3, and 2.7% as level 4 Dry Eye Workshop severity, whereas 44.9% of patients reported normal/mild symptoms, 17.1% with moderate severity, and 38.0% with severe DED. Patients were primarily treated with artificial tears. The clinician assessed 10.3% of patients as unchanged on disease severity after treatment and 88.0% as improved, whereas 49.2% of patients reported dry eye symptoms being almost the same after treatment and 34.6% reported improved symptoms. There was low agreement between clinician and patient assessments in terms of disease severity (rho = 0.17, P < 0.001) and treatment response (rho = 0.22, P < 0.001). There were marked differences in the degree of DED severity and treatment response between patient and clinician assessment. Clinicians may underestimate DED severity and persistence of dry eye symptoms after treatment with artificial tears.Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01942226.

  5. Comparison of treatment response in second-episode versus first-episode schizophrenia.

    PubMed

    Emsley, Robin; Oosthuizen, Petrus; Koen, Liezl; Niehaus, Dana; Martinez, Lupe

    2013-02-01

    This study investigated whether illness progression and treatment refractoriness emerge after relapse in schizophrenia. We compared outcomes in a cohort treated with a standardized protocol for the first and second episodes of illness. The sample comprised 31 participants who (1) had successfully completed a 2-year open-label treatment phase with risperidone long-acting injection (RLAI) for a first episode of schizophrenia; (2) underwent an intermittent treatment extension phase up to 3 years or until recurrence, and (3) entered a further 2-year treatment phase with RLAI for a recurrence episode. For the patients who remained in treatment (n = 14 [45%]), Positive and Negative Syndrome Scale score reductions, response rates, remission rates, time to response, time to remission, functional outcome scores, and modal RLAI doses were similar for the 2 treatment periods. However, 17 (55 %) of the 31 patients discontinued the study in the second episode compared with 14 (28%) of 50 patients in the first episode, suggesting reduced effectiveness of antipsychotics when reintroduced after illness recurrence. Most notably, emergent treatment nonresponsiveness was observed in 5 participants (16%), consistent with the hypothesis that relapse may be biologically harmful in a subset of patients.

  6. [Mantle cell lymphoma, response to treatment and prognosis in 45 patients].

    PubMed

    Sorigue, Marc; Sancho, Juan-Manuel; García, Olga; Vila, Jordi; Moreno, Miriam; Ribera, Josep-Maria

    2016-07-01

    Mantle cell lymphoma (MCL) is a rare lymphoproliferative disorder, with frequent relapses and a poor prognosis. This study analyzes response to treatment and prognosis in a series of MCL patients. Retrospective study of MCL patients diagnosed in a single institution between 1996 and 2013. The cohort was divided according to the treatment received. Forty-five patients were included (32 male) with a median age of 66 years old. Twenty-one received intensive chemotherapy or chemoimmunotherapy (based on high-dose cytarabine), 13 semi-intensive (without high-dose cytarabine), 8 not intensive and 3 did not require treatment. Overall response rate was 85% in the intensive and 77% in the semi-intensive treatment groups. In multivariate analysis, intensive treatment was correlated with a longer progression-free survival (hazard ratio 9.8 [95% CI 2.7-35.5], P=.001) and overall survival (4.5 [1.2-17.8], P=.03). In this retrospective series of MCL patients, intensive treatment was correlated with better outcomes than the other treatment modalities. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

  7. Trends in antiretroviral treatment use and treatment response in three Australian states in the first decade of combination antiretroviral treatment

    PubMed Central

    Falster, Kathleen; Gelgor, Linda; Shaik, Ansari; Zablotska, Iryna; Prestage, Garrett; Grierson, Jeffrey; Thorpe, Rachel; Pitts, Marian; Anderson, Jonathon; Chuah, John; Mulhall, Brian; Petoumenos, Kathy; Kelleher, Anthony; Law, Matthew G.

    2009-01-01

    Objectives To determine if there were any differences in antiretroviral treatment (ART) use across the three eastern states of Australia, New South Wales, Victoria and Queensland, during the period 1997 to 2006. Methods We used data from a clinic-based cohort, the Australian HIV Observational Database (AHOD), to determine the proportion of HIV-infected patients on ART in selected clinics in each state and the proportion of treated patients with an undetectable viral load. Data from the national Highly Specialised Drugs program and AHOD was used to estimate total numbers of individuals on ART and the proportion of individuals living with HIV on ART nationally and by state. Data from the HIV Futures Survey and the Gay Community Periodic Survey (GCPS) were used to determine the proportion of community-based men who have sex with men (MSM) on ART. The proportion of patients with primary HIV infection (PHI) who commenced ART within one year of diagnosis was obtained from the Acute Infection and Early Disease Research Program (AIEDRP) CORE01 protocol and Primary HIV and Early Disease Research: Australian cohort (PHAEDRA) cohorts. Results We estimated that the numbers of individuals on ART increased from 3,181 to 4,553 in NSW, 1,309 to 1,926 in Victoria and 809 to 1615 in Queensland between 2000 and 2006. However, these numbers may reflect a lower proportion of individuals living with HIV on ART in NSW compared to the other states (37% compared to 49 and 55% in 2000). We found similar proportions of HIV-positive MSM participants were on ART in all three states over the study period in the clinic-based AHOD cohort (81-92%) and two large, community based surveys in Australia (69-85% and 49-83%) . Similar proportions of treated patients had an undetectable viral load across the three states, with a consistently increasing trend over time observed in all states. We found that more PHI patients commenced treatment in the first year following HIV diagnosis in NSW compared to

  8. Trends in antiretroviral treatment use and treatment response in three Australian states in the first decade of combination antiretroviral treatment.

    PubMed

    Falster, Kathleen; Gelgor, Linda; Shaik, Ansari; Zablotska, Iryna; Prestage, Garrett; Grierson, Jeffrey; Thorpe, Rachel; Pitts, Marian; Anderson, Jonathan; Chuah, John; Mulhall, Brian; Petoumenos, Kathy; Kelleher, Anthony; Law, Matthew

    2008-06-01

    To determine if there were any differences in antiretroviral treatment (ART) use across the three eastern states of Australia, New South Wales (NSW), Victoria and Queensland, during the period 1997 to 2006. We used data from a clinic-based cohort, the Australian HIV Observational Database (AHOD), to determine the proportion of HIV-infected patients on ART in selected clinics in each state and the proportion of treated patients with an undetectable viral load. Data from the national Highly Specialised Drugs program and AHOD were used to estimate total numbers of individuals on ART and the proportion of individuals living with HIV on ART nationally and by state. Data from the HIV Futures Survey and the Gay Community Periodic Survey were used to determine the proportion of community-based men who have sex with men on ART. The proportion of patients with primary HIV infection (PHI) who commenced ART within 1 year of diagnosis was obtained from the Acute Infection and Early Disease Research Program (AIEDRP) CORE01 protocol and Primary HIV and Early Disease Research: Australian Cohort (PHAEDRA) cohorts. We estimated that the numbers of individuals on ART increased from 3181 to 4553 in NSW, 1309 to 1926 in Victoria and 809 to 1615 in Queensland between 2000 and 2006. However, these numbers may reflect a lower proportion of individuals living with HIV on ART in NSW compared with the other states (37% compared with 49 and 55% in 2000). We found similar proportions of HIV-positive men who have sex with men participants were on ART in all three states over the study period in the clinic-based AHOD cohort (81-92%) and two large, community-based surveys in Australia (69-85% and 49-83%). Similar proportions of treated patients had an undetectable viral load across the three states, with a consistently increasing trend over time observed in all states. We found that more PHI patients commenced treatment in the first year following HIV diagnosis in NSW compared with Victoria

  9. Expression of Interferon Effector Gene SART1 Correlates with Interferon Treatment Response against Hepatitis B Infection

    PubMed Central

    Li, Yong; Zhu, Chuanlong; Wang, Faxi; Zhu, Tiantian; Liu, Shufeng

    2016-01-01

    Interferon-α (IFN-α) has limited response rate in the treatment of chronic hepatitis B (CHB). The underlying mechanism of differential responsiveness to IFN remains elusive. It has been recently reported that SART1 mediates antiviral effects of IFN-α in the hepatitis C virus (HCV) cell culture model. In this study, we investigated the role of SART1 in antiviral activity of IFN-α against hepatitis B virus (HBV) using blood and liver biopsy samples from chronic hepatitis B patients treated with pegylated IFN-α and HepG2 cells transfected with cloned HBV DNA. We observed that the basal SART1 expression in liver and PBMCs before IFN treatment was significantly higher in responders than in nonresponders. Furthermore, baseline SART1 expression level positively correlated with the degree of HBV DNA and HBeAg decline after IFN treatment. Mechanistically, silencing SART1 abrogated the antiviral activity of IFN-α, reduced the expression of IFN-stimulated genes (ISGs) Mx, OAS, and PKR, and attenuated JAK-STAT signaling in HepG2 cells, suggesting that SART1 regulates IFN-mediated antiviral activity through JAK-STAT signaling and ISG expression. Our study elucidates the important role of SART1 in IFN-mediated anti-HBV response and provides new insights into understanding variation of IFN treatment response in CHB patients. PMID:28077916

  10. Mediation and Moderation of Psychological Pain Treatments: Response Expectancies and Hypnotic Suggestibility

    ERIC Educational Resources Information Center

    Milling, Leonard S.; Reardon, John M.; Carosella, Gina M.

    2006-01-01

    The mediator role of response expectancies and the moderator role of hypnotic suggestibility were evaluated in the analogue treatment of pain. Approximately 1,000 participants were assessed for hypnotic suggestibility. Later, as part of a seemingly unrelated experiment, 188 of these individuals were randomly assigned to distraction,…

  11. Primary non-small cell lung cancer response upon treatment with denosumab.

    PubMed

    Curioni-Fontecedro, A; Husmann, L; Soldini, D; Stahel, R A

    2013-12-01

    Here we report the case of a patient with metastatic adenocarcinoma of the lung harboring an ALK gene translocation. In this patient a response of the primary tumor and metastases has been detected upon treatment with denosumab. A possible link between ALK and RANK is postulated.

  12. Acute Time to Response in the Treatment for Adolescents with Depression Study (TADS)

    ERIC Educational Resources Information Center

    Kratochvil, Christopher; Emslie, Graham; Silva, Susan; McNulty, Steve; Walkup, John; Curry, John; Reinecke, Mark; Vitiello, Benedetto; Rohde, Paul; Feeny, Nora; Casat, Charles; Pathak, Sanjeev; Weller, Elizabeth; May, Diane; Mayes, Taryn; Robins, Michele; March, John

    2006-01-01

    Objective: To examine the time to response for both pharmacotherapy and psychotherapy in the Treatment for Adolescents with Depression Study (TADS). Method: Adolescents (N = 439, ages 12 to 17 years) with major depressive disorder were randomized to fluoxetine (FLX), cognitive-behavioral therapy (CBT), their combination (COMB), or pill placebo…

  13. Dose Response Effects of Lisdexamfetamine Dimesylate Treatment in Adults with ADHD: An Exploratory Study

    ERIC Educational Resources Information Center

    Faraone, Stephen V.; Spencer, Thomas J.; Kollins, Scott H.; Glatt, Stephen J.; Goodman, David

    2012-01-01

    Objective: To explore dose-response effects of lisdexamfetamine dimesylate (LDX) treatment for ADHD. Method: This was a 4-week, randomized, double-blinded, placebo-controlled, parallel-group, forced-dose titration study in adult participants, aged 18 to 55 years, meeting "Diagnostic and Statistical Manual of Mental Disorders" (4th ed., text rev.)…

  14. Improving Question-Asking Initiations in Young Children with Autism Using Pivotal Response Treatment

    ERIC Educational Resources Information Center

    Koegel, Robert L.; Bradshaw, Jessica L.; Ashbaugh, Kristen; Koegel, Lynn Kern

    2014-01-01

    Social initiations make up a core deficit for children with autism spectrum disorder (ASD). In particular, initiated questions during social interactions are often minimal or absent in this population. In the context of a multiple baseline design, the efficacy of using the motivational procedures of Pivotal Response Treatment to increase social…

  15. Habituation of Premonitory Sensations during Exposure and Response Prevention Treatment in Tourette's Syndrome

    ERIC Educational Resources Information Center

    Verdellen, Cara W. J.; Hoogduin, Cees A. L.; Kato, Bernet S.; Keijsers, Ger P. J.; Cath, Danielle C.; Hoijtink, Herbert B.

    2008-01-01

    Exposure to premonitory sensations and response prevention of tics (ER) has been shown to be a promising new treatment for Tourette's syndrome (TS). The present study tested the hypothesis that habituation to unpleasant premonitory sensations associated with the tic is an underlying mechanism of change in ER. Patients rated the severity of…

  16. Prediction of Response to Treatment in a Randomized Clinical Trial of Marital Therapy

    ERIC Educational Resources Information Center

    Atkins, David C.; Berns, Sara B.; George, William H.; Doss, Brian D.; Gattis, Krista; Christensen, Andrew

    2005-01-01

    This study investigated demographic, intrapersonal, and interpersonal predictors of treatment response in a randomized clinical trial of 134 distressed married couples, which examined traditional (N. S. Jacobson & G. Margolin, 1979) and integrative (N. S. Jacobson & A. Christensen, 1996) behavioral couple therapy. Results based on hierarchical…

  17. The Effects of a Response Cost Treatment Tactic on Hyperactive Children.

    ERIC Educational Resources Information Center

    Rapport, Mark D.; And Others

    1980-01-01

    Tested a response cost procedure, compared with Ritalin treatment, on hyperactive elementary school children to determine effectiveness in reducing hyperactive behavior and in increasing academic performance. The cost program alone and combined with medication were effective in reducing off-task behavior and in increasing academic performance.…

  18. Predictors of Treatment Response to Cognitive-Behavioral Therapy for Depression in Parkinson's Disease

    ERIC Educational Resources Information Center

    Dobkin, Roseanne D.; Rubino, Jade Tiu; Allen, Lesley A.; Friedman, Jill; Gara, Michael A.; Mark, Margery H.; Menza, Matthew

    2012-01-01

    Objective: The purpose of this study was to examine predictors of treatment response to cognitive-behavioral therapy (CBT) for depression in Parkinson's disease (PD). Method: The sample comprised 80 depressed ("DSM-IV" criteria) adults with PD (60% male) and their caregivers who participated in an National Institutes of Health-sponsored…

  19. 21 CFR 1230.15 - Responsibility for labeling directions for treatment.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Responsibility for labeling directions for treatment. 1230.15 Section 1230.15 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) REGULATIONS UNDER CERTAIN OTHER ACTS ADMINISTERED BY THE FOOD AND...

  20. Pivotal Response Treatment for Children with Autism: Core Principles and Applications for School Psychologists

    ERIC Educational Resources Information Center

    Renshaw, Tyler L.; Kuriakose, Sarah

    2011-01-01

    During the past 2 decades, pivotal response treatment (PRT) has emerged as an evidence-based methodology for intervening with the behavioral, communicative, social, and academic impairments of children with autism. Unlike other highly structured behavioral interventions for autism, PRT emphasizes principles over procedures and focuses on enhancing…

  1. Mediation and Moderation of Psychological Pain Treatments: Response Expectancies and Hypnotic Suggestibility

    ERIC Educational Resources Information Center

    Milling, Leonard S.; Reardon, John M.; Carosella, Gina M.

    2006-01-01

    The mediator role of response expectancies and the moderator role of hypnotic suggestibility were evaluated in the analogue treatment of pain. Approximately 1,000 participants were assessed for hypnotic suggestibility. Later, as part of a seemingly unrelated experiment, 188 of these individuals were randomly assigned to distraction,…

  2. Evaluation of genotypic variation of broccoli (brassica oleracea var. italic) in response to selenium treatment

    USDA-ARS?s Scientific Manuscript database

    Broccoli (Brassica oleracea var. italic) fortified with selenium (Se) has been promoted as a functional food. Here we evaluated 38 broccoli accessions for their capacity to accumulate Se and for their responses to selenate treatment in terms of nutritional qualities and sulfur gene expression. We fo...

  3. The Effects of Response Effort on Safe Performance by Therapists at an Autism Treatment Facility

    ERIC Educational Resources Information Center

    Casella, Sarah E.; Wilder, David A.; Neidert, Pamela; Rey, Catalina; Compton, Megan; Chong, Ivy

    2010-01-01

    The effects of response effort on safe behaviors (i.e., glove wearing, hand sanitizing, and electrical outlet replacement) exhibited by therapists at an autism treatment center were examined. Participants were exposed to 2 or 3 levels of effort (i.e., high, medium, low) for each dependent variable. Results showed increased safe performance during…

  4. Improving Question-Asking Initiations in Young Children with Autism Using Pivotal Response Treatment

    ERIC Educational Resources Information Center

    Koegel, Robert L.; Bradshaw, Jessica L.; Ashbaugh, Kristen; Koegel, Lynn Kern

    2014-01-01

    Social initiations make up a core deficit for children with autism spectrum disorder (ASD). In particular, initiated questions during social interactions are often minimal or absent in this population. In the context of a multiple baseline design, the efficacy of using the motivational procedures of Pivotal Response Treatment to increase social…

  5. Peer-Mediated Pivotal Response Treatment for Young Children with Autism Spectrum Disorders: A Systematic Review

    ERIC Educational Resources Information Center

    Boudreau, Ainsley M.; Corkum, Penny; Meko, Katelyn; Smith, Isabel M.

    2015-01-01

    This review examined the effectiveness of peer-mediated pivotal response treatment (PM-PRT) to increase social-communication skills for children with autism spectrum disorders (ASD). A systematic review was conducted of all published studies examining PM-PRT in school-aged children with ASD, based on an established rubric. Five PM-PRT studies…

  6. Molecular Targeted Therapy in Modern Oncology: Imaging Assessment of Treatment Response and Toxicities

    PubMed Central

    Braschi-Amirfarzan, Marta; DiPiro, Pamela J.; Jagannathan, Jyothi P.; Shinagare, Atul B.

    2017-01-01

    Oncology is a rapidly evolving field with a shift toward personalized cancer treatment. The use of therapies targeted to the molecular features of individual tumors and the tumor microenvironment has become much more common. In this review, anti-angiogenic and other molecular targeted therapies are discussed, with a focus on typical and atypical response patterns and imaging manifestations of drug toxicities. PMID:28096716

  7. Dose Response Effects of Lisdexamfetamine Dimesylate Treatment in Adults with ADHD: An Exploratory Study

    ERIC Educational Resources Information Center

    Faraone, Stephen V.; Spencer, Thomas J.; Kollins, Scott H.; Glatt, Stephen J.; Goodman, David

    2012-01-01

    Objective: To explore dose-response effects of lisdexamfetamine dimesylate (LDX) treatment for ADHD. Method: This was a 4-week, randomized, double-blinded, placebo-controlled, parallel-group, forced-dose titration study in adult participants, aged 18 to 55 years, meeting "Diagnostic and Statistical Manual of Mental Disorders" (4th ed., text rev.)…

  8. Peer-Mediated Pivotal Response Treatment for Young Children with Autism Spectrum Disorders: A Systematic Review

    ERIC Educational Resources Information Center

    Boudreau, Ainsley M.; Corkum, Penny; Meko, Katelyn; Smith, Isabel M.

    2015-01-01

    This review examined the effectiveness of peer-mediated pivotal response treatment (PM-PRT) to increase social-communication skills for children with autism spectrum disorders (ASD). A systematic review was conducted of all published studies examining PM-PRT in school-aged children with ASD, based on an established rubric. Five PM-PRT studies…

  9. How Attendance and Quality of Participation Affect Treatment Response to Parent Management Training

    ERIC Educational Resources Information Center

    Nix, Robert L.; Bierman, Karen L.; McMahon, Robert J.

    2009-01-01

    This study examined whether attendance and quality of participation in parent management training predicted treatment response. Data were from 445 parents (55% minority, 62% single; almost all of low socioeconomic status) who had 1st-grade children with severe conduct problems. Quality of participation in weekly parent groups was based on group…

  10. Pivotal Response Treatment for Children with Autism: Core Principles and Applications for School Psychologists

    ERIC Educational Resources Information Center

    Renshaw, Tyler L.; Kuriakose, Sarah

    2011-01-01

    During the past 2 decades, pivotal response treatment (PRT) has emerged as an evidence-based methodology for intervening with the behavioral, communicative, social, and academic impairments of children with autism. Unlike other highly structured behavioral interventions for autism, PRT emphasizes principles over procedures and focuses on enhancing…

  11. Statin use and 25-hydroxyvitamin D blood level response to vitamin D treatment of older adults

    USDA-ARS?s Scientific Manuscript database

    Objectives: To determine whether statin use alters response of 25-hydroxyvitamin D (25(OH)D) level to vitamin D treatment. Design: Pooled analysis. Setting: Three double-blind randomized controlled trials that tested different doses of vitamin D. Participants: Participants of three trials (N = 646; ...

  12. The Effects of a Response Cost Treatment Tactic on Hyperactive Children.

    ERIC Educational Resources Information Center

    Rapport, Mark D.; And Others

    1980-01-01

    Tested a response cost procedure, compared with Ritalin treatment, on hyperactive elementary school children to determine effectiveness in reducing hyperactive behavior and in increasing academic performance. The cost program alone and combined with medication were effective in reducing off-task behavior and in increasing academic performance.…

  13. Understory vegetation response to mechanical mastication and other fuels treatments in a ponderosa pine forest

    Treesearch

    Jeffrey M. Kane; J. Morgan Varner; Eric E. Knapp

    2010-01-01

    Questions: What influence does mechanical mastication and other fuel treatments have on: (1) canopy and forest floor response variables that influence understory plant development; (2) initial understory vegetation cover, diversity, and composition; and (3) shrub and non-native species density in a secondgrowth ponderosa pine forest....

  14. [The responsibility of the emergency service physician and patient consent to treatment and hospitalization].

    PubMed

    Wiernikowski, A; Szczepanek, M

    1997-01-01

    Amenability of emergency service physician for the treatment given without patient consent has been presented in the study. Depending on circumstances it can be penal, civil, disciplinary and professional responsibility. The study has been annotated with current legal and ethical rules, which should be not only commonly known to physicians but also respected to avoid legal consequences.

  15. Pivotal Response Treatment for Infants At-Risk for Autism Spectrum Disorders: A Pilot Study

    ERIC Educational Resources Information Center

    Steiner, Amanda Mossman; Gengoux, Grace W.; Klin, Ami; Chawarska, Katarzyna

    2013-01-01

    Presently there is limited research to suggest efficacious interventions for infants at-risk for autism. Pivotal response treatment (PRT) has empirical support for use with preschool children with autism, but there are no reports in the literature utilizing this approach with infants. In the current study, a developmental adaptation of PRT was…

  16. Predictors of Treatment Response to Cognitive-Behavioral Therapy for Depression in Parkinson's Disease

    ERIC Educational Resources Information Center

    Dobkin, Roseanne D.; Rubino, Jade Tiu; Allen, Lesley A.; Friedman, Jill; Gara, Michael A.; Mark, Margery H.; Menza, Matthew

    2012-01-01

    Objective: The purpose of this study was to examine predictors of treatment response to cognitive-behavioral therapy (CBT) for depression in Parkinson's disease (PD). Method: The sample comprised 80 depressed ("DSM-IV" criteria) adults with PD (60% male) and their caregivers who participated in an National Institutes of Health-sponsored…

  17. Therapeutic Responses of Psychopathic Sexual Offenders: Treatment Attrition, Therapeutic Change, and Long-Term Recidivism

    ERIC Educational Resources Information Center

    Olver, Mark E.; Wong, Stephen C. P.

    2009-01-01

    The authors examined the therapeutic responses of psychopathic sex offenders (greater than or equal to 25 Psychopathy Checklist-Revised; PCL-R) in terms of treatment dropout and therapeutic change, as well as sexual and violent recidivism over a 10-year follow-up among 156 federally incarcerated sex offenders treated in a high-intensity inpatient…

  18. Prediction of Response to Treatment in a Randomized Clinical Trial of Marital Therapy

    ERIC Educational Resources Information Center

    Atkins, David C.; Berns, Sara B.; George, William H.; Doss, Brian D.; Gattis, Krista; Christensen, Andrew

    2005-01-01

    This study investigated demographic, intrapersonal, and interpersonal predictors of treatment response in a randomized clinical trial of 134 distressed married couples, which examined traditional (N. S. Jacobson & G. Margolin, 1979) and integrative (N. S. Jacobson & A. Christensen, 1996) behavioral couple therapy. Results based on hierarchical…

  19. Therapeutic Responses of Psychopathic Sexual Offenders: Treatment Attrition, Therapeutic Change, and Long-Term Recidivism

    ERIC Educational Resources Information Center

    Olver, Mark E.; Wong, Stephen C. P.

    2009-01-01

    The authors examined the therapeutic responses of psychopathic sex offenders (greater than or equal to 25 Psychopathy Checklist-Revised; PCL-R) in terms of treatment dropout and therapeutic change, as well as sexual and violent recidivism over a 10-year follow-up among 156 federally incarcerated sex offenders treated in a high-intensity inpatient…

  20. Habituation of Premonitory Sensations during Exposure and Response Prevention Treatment in Tourette's Syndrome

    ERIC Educational Resources Information Center

    Verdellen, Cara W. J.; Hoogduin, Cees A. L.; Kato, Bernet S.; Keijsers, Ger P. J.; Cath, Danielle C.; Hoijtink, Herbert B.

    2008-01-01

    Exposure to premonitory sensations and response prevention of tics (ER) has been shown to be a promising new treatment for Tourette's syndrome (TS). The present study tested the hypothesis that habituation to unpleasant premonitory sensations associated with the tic is an underlying mechanism of change in ER. Patients rated the severity of…

  1. Ghrelin Serum Concentrations Are Associated with Treatment Response During Lithium Augmentation of Antidepressants

    PubMed Central

    Bopp, Sandra; Schlattmann, Peter; Himmerich, Hubertus; Bschor, Tom; Richter, Christoph; Elstner, Samuel; Stamm, Thomas J; Schulz-Ratei, Brigitte; Lingesleben, Alexandra; Reischies, Friedel M; Sterzer, Philipp; Borgwardt, Stefan; Bauer, Michael; Heinz, Andreas; Hellweg, Rainer; Lang, Undine E; Adli, Mazda

    2017-01-01

    Abstract Background Lithium augmentation of antidepressants is an effective strategy in treatment-resistant depression. The proteohormone ghrelin is thought to be involved in the pathophysiology of depression. The purpose of this study was to investigate the association of treatment response with the course of ghrelin levels during lithium augmentation. Method Ghrelin serum concentrations and severity of depression were measured in 85 acute depressive patients before and after 4 weeks of lithium augmentation. Results In a linear mixed model analysis, we found a significant effect of response*time interaction (F1.81=9.48; P=.0028): under treatment, ghrelin levels increased in nonresponders and slightly decreased in responders to lithium augmentation. The covariate female gender had a significant positive effect (F1.83=4.69; P=.033), whereas time, response, appetite, and body mass index (kg/m2) did not show any significant effect on ghrelin levels (P>.05). Conclusion This is the first study showing that the course of ghrelin levels separates responders and nonresponders to lithium augmentation. Present results support the hypothesis that ghrelin serum concentrations might be involved in response to pharmacological treatment of depression.

  2. Time to response to citalopram treatment for agitation in Alzheimer's disease

    PubMed Central

    Weintraub, Daniel; Drye, Lea T.; Porsteinsson, Anton P.; Rosenberg, Paul B.; Pollock, Bruce G.; Devanand, D.P.; Frangakis, Constantine; Ismail, Zahinoor; Marano, Christopher; Meinert, Curtis L.; Mintzer, Jacobo E.; Munro, Cynthia A.; Pelton, Gregory; Rabins, Peter V.; Schneider, Lon S.; Shade, David M.; Yesavage, Jerome; Lyketsos, Constantine G.

    2015-01-01

    Background Agitation is a common and significant problem in Alzheimer’s disease (AD). In the recent Citalopram for Agitation in Alzheimer’s Disease (CitAD) study, citalopram was efficacious for the treatment of AD agitation. Here we examined the time course and predictors of response to treatment. Methods Response in CitAD was defined as a modified Alzheimer Disease Cooperative Study-Clinical Global Impression of Change (mADCS-CGIC) score of 1 or 2, or a Neurobehavioral Rating Scale agitation subscale (NBRS-A) score reduction ≥50% from baseline. “Stable early response” was defined as meeting the aforementioned criteria at both weeks 3 and 9, “late response” was response at week 9 but not at week 3, and “unstable response” was response at week 3 but not at week 9. Results In the primary analyses, citalopram was superior to placebo on both the CGIC and the NBRS-A response measures. There were little between-group differences in response rates in the first three weeks of the study (21% vs 19% on the CGIC). Citalopram patients were more likely than placebo patients to be a late responder (18% vs. 8% on CGIC, Fisher’s exact p=0.09; 31% vs. 15% on NBRS-A, Fisher’s exact p=0.02). Approximately half (45–56%) of citalopram responders at end-of-study achieved response later in the study, compared with 30–44% of placebo responders. Discussion Treatment with citalopram for agitation in AD needs to be at least nine weeks in duration to allow sufficient time for full response, and study duration is an important factor to consider in the design of clinical trials for agitation in Alzheimer’s disease. PMID:26238225

  3. The effect of hypofractionated radiation and magnetic nanoparticle hyperthermia on tumor immunogenicity and overall treatment response

    NASA Astrophysics Data System (ADS)

    Hoopes, P. Jack; Wagner, Robert J.; Song, Ailin; Osterberg, Bjorn; Gladstone, David J.; Bursey, Alicea A.; Fiering, Steven N.; Giustini, Andrew J.

    2017-02-01

    It is now known that many tumors develop molecular signals (immune checkpoint modulators) that inhibit an effective tumor immune response. New information also suggest that even well-known cancer treatment modalities such as radiation and hyperthermia generate potentially beneficial immune responses that have been blocked or mitigated by such immune checkpoints, or similar molecules. The cancer therapy challenge is to; a) identify these treatment-based immune signals (proteins, antigens, etc.); b) the treatment doses or regimens that produce them; and c) the mechanisms that block or have the potential to promote them. The goal of this preliminary study, using the B6 mouse - B16 tumor model, clinically relevant radiation doses and fractionation schemes (including those used clinically in hypofractionated radiation therapy), magnetic nanoparticle hyperthermia (mNPH) and sophisticated protein, immune and tumor growth analysis techniques and modulators, is to determine the effect of specific radiation or hyperthermia alone and combined on overall treatment efficacy and immunologic response mechanisms. Preliminary analysis suggests that radiation dose (10 Gy vs. 2 Gy) significantly alters the mechanism of cell death (apoptosis vs. mitosis vs. necrosis) and the resulting immunogenicity. Our hypothesis and data suggest this difference is protein/antigen and immune recognition-based. Similarly, our evidence suggest that radiation doses larger than the conventional 2 Gy dose and specific hyperthermia doses and techniques (including mNP hyperthermia treatment) can be immunologically different, and potentially superior to, the radiation and heat therapy regimens that are typically used in research and clinical practice.

  4. Dissociation predicts treatment response in eye-movement desensitization and reprocessing for posttraumatic stress disorder.

    PubMed

    Bae, Hwallip; Kim, Daeho; Park, Yong Chon

    2016-01-01

    Using clinical data from a specialized trauma clinic, this study investigated pretreatment clinical factors predicting response to eye-movement desensitization and reprocessing (EMDR) among adult patients diagnosed with posttraumatic stress disorder (PTSD). Participants were evaluated using the Clinician-Administered PTSD Scale (CAPS), the Symptom Checklist-90-Revised, the Beck Depression Inventory, and the Dissociative Experiences Scale before treatment and were reassessed using the CAPS after treatment and at 6-month follow-up. A total of 69 patients underwent an average of 4 sessions of EMDR, and 60 (87%) completed the posttreatment evaluation, including 8 participants who terminated treatment prematurely. Intent-to-treat analysis revealed that 39 (65%) of the 60 patients were classified as responders and 21 (35%) as nonresponders when response was defined as more than a 30% decrease in total CAPS score. The nonresponders had higher levels of dissociation (depersonalization and derealization) and numbing symptoms, but other PTSD symptoms, such as avoidance, hyperarousal, and intrusion, were not significantly different. The number of psychiatric comorbidities was also associated with treatment nonresponse. The final logistic regression model yielded 2 significant variables: dissociation (p < .001) and more than 2 comorbidities compared to none (p < .05). These results indicate that complex symptom patterns in PTSD may predict treatment response and support the inclusion of the dissociative subtype of PTSD in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition.

  5. Presentation of typhoid fever patients in Hazara Division and response to different treatment regimens.

    PubMed

    Nazar, Hassan Shahzad; Rabbani, Aftab; Riaz, Adeel; Anwar, Jasim

    2005-01-01

    Response to treatment can vary in patients with typhoid fever. This study was carried out on a group of typhoid patients who were treated in Medical B ward of Ayub Teaching Hospital. Resistance to antibiotic is commonly acquired by Salmonella typhi and is widely reported. Objective of study was to identify such resistance in patients coming from parts of Hazara Division. All patients who presented with typhoid fever and admitted to Medical B Unit from 1st July to 30th September 2002 were included in study. Out of 76 patients 46 (60%) were male. Epidemiological date, presenting symptoms, finding on physical examination, laboratory investigation and radiological examination were recorded. Then one of six commonly used treatment regimens were started. Response to treatment was studied. Common presenting symptoms and signs were recorded. Headache and fever were seen in 100% of patients. Cough and hypotension were among presenting features in 65% of patients. Leucocyte count of Less than 4 x 10(3)/dl was seen in 11% of samples. Liver functions and Renal function were found altered in 30% of patients. Study of response pattern to different regimens suggested relatively poor response to flouroquinolones. Fever of those patients who were treated with chloamphenicol and cefexime, settled early as compared to patients on other regimens. In addition to well known presenting features of typhoid like headache, fever, cough, hypotension and leucopenia abnormalities of renal and liver functions were commonly seen. Response to quinolone was poor suggesting emergence of resistance of salmonella typhi in this area.

  6. Identifying and Investigating Unexpected Response to Treatment: A Diabetes Case Study.

    PubMed

    Ozery-Flato, Michal; Ein-Dor, Liat; Parush-Shear-Yashuv, Naama; Aharonov, Ranit; Neuvirth, Hani; Kohn, Martin S; Hu, Jianying

    2016-09-01

    The availability of electronic health records creates fertile ground for developing computational models of various medical conditions. We present a new approach for detecting and analyzing patients with unexpected responses to treatment, building on machine learning and statistical methodology. Given a specific patient, we compute a statistical score for the deviation of the patient's response from responses observed in other patients having similar characteristics and medication regimens. These scores are used to define cohorts of patients showing deviant responses. Statistical tests are then applied to identify clinical features that correlate with these cohorts. We implement this methodology in a tool that is designed to assist researchers in the pharmaceutical field to uncover new features associated with reduced response to a treatment. It can also aid physicians by flagging patients who are not responding to treatment as expected and hence deserve more attention. The tool provides comprehensive visualizations of the analysis results and the supporting data, both at the cohort level and at the level of individual patients. We demonstrate the utility of our methodology and tool in a population of type II diabetic patients, treated with antidiabetic drugs, and monitored by the HbA1C test.

  7. EEG-arousal regulation as predictor of treatment response in patients suffering from obsessive compulsive disorder.

    PubMed

    Dohrmann, Anna-Lena; Stengler, Katarina; Jahn, Ina; Olbrich, Sebastian

    2017-10-01

    Aim of this study was to analyze whether electroencephalogram (EEG)-based CNS-arousal markers differ for patients suffering from obsessive compulsive disorder (OCD) that either respond or do not respond to cognitive behavioral therapy (CBT), selective serotonin reuptake inhibitors (SSRIs) or their combination. Further the study aimed to identify specific response-predictors for the different therapy approaches. CNS-arousal from 51 unmedicated patients during fifteen-minute resting state was assessed using VIGALL (Vigilance Algorithm Leipzig). Clinical Global Impression (CGI) scores were used to assess response or non-response after three to six months following therapy (CBT, n=18; SSRI, n=11 or combination, n=22). Differences between Responders (R) and Non-Responders (NR) were identified using multivariate analysis of covariance (MANCOVA) models. MANCOVA revealed that Responders spent significant less time at the highest CNS-arousal stage 0. Further, low amounts of the highest CNS-arousal stages were specifically predictive for a response to a combined treatment approach. The fact that CNS-arousal markers allowed discrimination between Responders and Non-Responders and also between Responders of different treatment arms underlines a possible clinical value of EEG-based markers. These results encourage further research on EEG-arousal regulation for determining pathophysiological subgroups for treatment response. Copyright © 2017 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

  8. Genomic profiling of the response of Candida albicans to itraconazole treatment using a DNA microarray.

    PubMed

    De Backer, M D; Ilyina, T; Ma, X J; Vandoninck, S; Luyten, W H; Vanden Bossche, H

    2001-06-01

    The application of genome-wide expression profiling to determine how drugs achieve their therapeutic effect has provided the pharmaceutical industry with an exciting new tool for drug mode-of-action studies. We used DNA chip technology to study cellular responses to perturbations of ergosterol biosynthesis caused by the broad-spectrum antifungal agent itraconazole. Simultaneous examination of over 6,600 Candida albicans gene transcript levels, representing the entire genome, upon treatment of cells with 10 microM itraconazole revealed that 296 genes were responsive. For 116 genes transcript levels were decreased at least 2.5-fold, while for 180 transcript levels were similarly increased. A global upregulation of ERG genes in response to azole treatment was observed. ERG11 and ERG5 were found to be upregulated approximately 12-fold. In addition, a significant upregulation was observed for ERG6, ERG1, ERG3, ERG4, ERG10, ERG9, ERG26, ERG25, ERG2, IDII, HMGS, NCP1, and FEN2, all of which are genes known to be involved in ergosterol biosynthesis. The effects of itraconazole on a wide variety of known metabolic processes are discussed. As over 140 proteins with unknown function were responsive to itraconazole, our analysis might provide-in combination with phenotypic data-first hints of their potential function. The present report is the first to describe the application of DNA chip technology to study the response of a major human fungal pathogen to drug treatment.

  9. Final responsibility for treatment choice: the proper role of medical doctors?

    PubMed

    Holm, Søren

    2011-06-01

    To analyse whether the traditional allocation of decision-making responsibility is still justifiable. And, if not to analyse the strength of claims made by other health care professions and by patients. Traditionally doctors have been responsible for choices of treatment, both in terms of deciding and in terms of taking responsibility for the decisions. But modern health care work often takes place in teams involving health care professionals from different professions as well as the patient. In such teams it may not be obvious who should be responsible for treatment choice. Philosophical analysis of epistemic, ethical and organizational arguments, including analysis of the historical origins of these arguments. The epistemic, ethical and organizational arguments for maintaining a primary decision making role for doctors are not sound. Other health care professionals can, in some circumstances make stronger and more justified claims. The arguments against allocation decision making authority to patients are also invalid or unsound in many circumstances. There are many situations in which final responsibility for treatment choice should rest with health care professionals who are not doctors and with patients. © 2011 Blackwell Publishing Ltd.

  10. Genomic Profiling of the Response of Candida albicans to Itraconazole Treatment Using a DNA Microarray

    PubMed Central

    De Backer, Marianne D.; Ilyina, Tatiana; Ma, Xiao-Jun; Vandoninck, Sandy; Luyten, Walter H. M. L.; Vanden Bossche, Hugo

    2001-01-01

    The application of genome-wide expression profiling to determine how drugs achieve their therapeutic effect has provided the pharmaceutical industry with an exciting new tool for drug mode-of-action studies. We used DNA chip technology to study cellular responses to perturbations of ergosterol biosynthesis caused by the broad-spectrum antifungal agent itraconazole. Simultaneous examination of over 6,600 Candida albicans gene transcript levels, representing the entire genome, upon treatment of cells with 10 μM itraconazole revealed that 296 genes were responsive. For 116 genes transcript levels were decreased at least 2.5-fold, while for 180 transcript levels were similarly increased. A global upregulation of ERG genes in response to azole treatment was observed. ERG11 and ERG5 were found to be upregulated approximately 12-fold. In addition, a significant upregulation was observed for ERG6, ERG1, ERG3, ERG4, ERG10, ERG9, ERG26, ERG25, ERG2, IDII, HMGS, NCP1, and FEN2, all of which are genes known to be involved in ergosterol biosynthesis. The effects of itraconazole on a wide variety of known metabolic processes are discussed. As over 140 proteins with unknown function were responsive to itraconazole, our analysis might provide—in combination with phenotypic data—first hints of their potential function. The present report is the first to describe the application of DNA chip technology to study the response of a major human fungal pathogen to drug treatment. PMID:11353609

  11. Magnetic Resonance Imaging Predictors of Treatment Response in First-Episode Schizophrenia

    PubMed Central

    Szeszko, Philip R.; Narr, Katherine L.; Phillips, Owen R.; McCormack, Joanne; Sevy, Serge; Gunduz-Bruce, Handan; Kane, John M.; Bilder, Robert M.; Robinson, Delbert G.

    2012-01-01

    Identifying neurobiological predictors of response to antipsychotics in patients with schizophrenia is a critical goal of translational psychiatry. Few studies, however, have investigated the relationship between indices of brain structure and treatment response in the context of a controlled clinical trial. In this study, we sought to identify magnetic resonance (MR) imaging measures of the brain that predict treatment response in patients experiencing a first-episode of schizophrenia. Structural MR imaging scans were acquired in 39 patients experiencing a first-episode of schizophrenia with minimal or no prior exposure to antipsychotics participating in a double-blind 16-week clinical trial comparing the efficacy of risperidone vs olanzapine. Twenty-five patients were classified as responders by meeting operationally defined treatment response criteria on 2 consecutive study visits. Fourteen patients never responded to antipsychotic medication at any point during the clinical trial. MR imaging scans were also acquired in 45 age- and sex-matched healthy volunteers. Cortical pattern matching methods were used to compare cortical thickness and asymmetry measures among groups. Statistical mapping results, confirmed by permutation testing, indicated that responders had greater cortical thickness in occipital regions and greater frontal cortical asymmetry compared with nonresponders. Moreover, among responders, greater thickness in temporal regions was associated with less time to respond. Our findings are consistent with the hypothesis that plasticity and cortical thickness may be more preserved in responders and that MR imaging may assist in the prediction of antipsychotic drug response in patients experiencing a first-episode of schizophrenia. PMID:21084552

  12. Magnetic resonance imaging predictors of treatment response in first-episode schizophrenia.

    PubMed

    Szeszko, Philip R; Narr, Katherine L; Phillips, Owen R; McCormack, Joanne; Sevy, Serge; Gunduz-Bruce, Handan; Kane, John M; Bilder, Robert M; Robinson, Delbert G

    2012-05-01

    Identifying neurobiological predictors of response to antipsychotics in patients with schizophrenia is a critical goal of translational psychiatry. Few studies, however, have investigated the relationship between indices of brain structure and treatment response in the context of a controlled clinical trial. In this study, we sought to identify magnetic resonance (MR) imaging measures of the brain that predict treatment response in patients experiencing a first-episode of schizophrenia. Structural MR imaging scans were acquired in 39 patients experiencing a first-episode of schizophrenia with minimal or no prior exposure to antipsychotics participating in a double-blind 16-week clinical trial comparing the efficacy of risperidone vs olanzapine. Twenty-five patients were classified as responders by meeting operationally defined treatment response criteria on 2 consecutive study visits. Fourteen patients never responded to antipsychotic medication at any point during the clinical trial. MR imaging scans were also acquired in 45 age- and sex-matched healthy volunteers. Cortical pattern matching methods were used to compare cortical thickness and asymmetry measures among groups. Statistical mapping results, confirmed by permutation testing, indicated that responders had greater cortical thickness in occipital regions and greater frontal cortical asymmetry compared with nonresponders. Moreover, among responders, greater thickness in temporal regions was associated with less time to respond. Our findings are consistent with the hypothesis that plasticity and cortical thickness may be more preserved in responders and that MR imaging may assist in the prediction of antipsychotic drug response in patients experiencing a first-episode of schizophrenia.

  13. Effect of nabumetone treatment on vascular responses of the thoracic aorta in rat experimental arthritis.

    PubMed

    Ulker, S; Onal, A; Hatip, F B; Sürücü, A; Alkanat, M; Koşay, S; Evinç, A

    2000-04-01

    Nabumetone is a nonsteroidal anti-inflammatory (NSAI) drug which is known to cause less gastrointestinal damage than other NSAI drugs. This study was performed to evaluate whether nabumetone treatment might alter the vascular aberrations related to inflammation in a rat model of adjuvant-induced arthritis. Nabumetone treatment (120 or 240 mg x kg(-1) x day(-1), orally) was initiated on the 15th day of adjuvant inoculation and continued for 14 days. Arthritic lesions, vascular contractile and relaxant responses and gastroduodenal histopathological preparations were evaluated 29 days after adjuvant inoculation. The contractile responses of aortic rings to phenylephrine and KCl were increased in grade 2 arthritic rats. In grade 3 arthritis only the phenylephrine contractility was decreased. The relaxant responses to acetylcholine and sodium nitroprusside were decreased in grades 2 and 3. In healthy rats, nabumetone did not change the vascular responses. After treatment of arthritic rats with nabumetone, both the contractile and relaxant response of the aortic rings returned to normal, and arthritic score and paw swelling were reduced. Gastroduodenal histopathology did not show erosions or ulcers in any of the groups. In conclusion, nabumetone improved the systemic signs and vascular alterations in experimental arthritis without showing any gastrointestinal side effects.

  14. Sex influences immune responses to viruses, and efficacy of prophylaxis and treatments for viral diseases.

    PubMed

    Klein, Sabra L

    2012-12-01

    The intensity and prevalence of viral infections are typically higher in males, whereas disease outcome can be worse for females. Females mount higher innate and adaptive immune responses than males, which can result in faster clearance of viruses, but also contributes to increased development of immunopathology. In response to viral vaccines, females mount higher antibody responses and experience more adverse reactions than males. The efficacy of antiviral drugs at reducing viral load differs between the sexes, and the adverse reactions to antiviral drugs are typically greater in females than males. Several variables should be considered when evaluating male/female differences in responses to viral infection and treatment: these include hormones, genes, and gender-specific factors related to access to, and compliance with, treatment. Knowledge that the sexes differ in their responses to viruses and to treatments for viral diseases should influence the recommended course of action differently for males and females. Editor's suggested further reading in BioEssays X-chromosome-located microRNAs in immunity: Might they explain male/female differences Abstract.

  15. Computerized EEG as a predictor of drug response in treatment resistant schizophrenics.

    PubMed

    Itil, T M; Shapiro, D; Schneider, S J; Francis, I B

    1981-10-01

    Thirteen chronic schizophrenics were identified who failed to improve with physician's choice medication and 1 year of systematic treatment with a long acting phenothiazine. These patients were considered to be treatment resistant. Computer analyzed electroencephalogram (CEEG) or these treatment resistant schizophrenics was characterized by a large amount of alpha activity and less fast activity, in comparison with previous results from therapy responsive schizophrenics. The therapy resistant subjects did not display the typical neuroleptic CEEG profile following test dosages of four neuroleptics, and instead displayed CEEG profiles which more closely resembled the typical profile for psychostimulants. These findings may point to an altered metabolism, neurotransmitter defect, or other problem which alters the physiological and clinical response of therapy resistant schizophrenics to neuroleptic medication.

  16. Clinical manifestations and treatment response of steroid in pediatric Hashimoto encephalopathy.

    PubMed

    Yu, Hee Joon; Lee, Jeehun; Seo, Dae Won; Lee, Munhyang

    2014-07-01

    Hashimoto encephalopathy is a steroid-responsive encephalopathy associated with elevated titers of antithyroid antibodies. Clinical symptoms are characterized by behavioral and cognitive changes, speech disturbance, seizures, myoclonus, psychosis, hallucination, involuntary movements, cerebellar signs, and coma. The standard treatment is the use of corticosteroids along with the treatment of any concurrent dysthyroidism. Other options are immunoglobulins and plasmapheresis. We described symptoms and outcomes on 3 teenage girls with Hashimoto encephalopathy. Presenting symptoms were seizure or altered mental status. One patient took levothyroxine due to hypothyroidism before presentation of Hashimoto encephalopathy. After confirmation of elevated antithyroid antibodies, all patients were treated with steroids. One patient needed plasmapheresis because of the lack of response to steroids and immunoglobulins. Hashimoto encephalopathy should be considered in any patient presenting with acute or subacute unexplained encephalopathy and seizures. Even though the use of steroids is the first line of treatment, plasmapheresis can rescue steroid-resistant patients. © The Author(s) 2013.

  17. Treatment-induced cell cycle kinetics dictate tumor response to chemotherapy

    PubMed Central

    Hallett, Robin M.; Huang, Cheng; Motazedian, Ali; Auf der Mauer, Stefanie; Pond, Gregory R.; Hassell, John A.; Nordon, Robert E.; Draper, Jonathan S.

    2015-01-01

    Chemotherapy fails to provide durable cure for the majority of cancer patients. To identify mechanisms associated with chemotherapy resistance, we identified genes differentially expressed before and after chemotherapeutic treatment of breast cancer patients. Treatment response resulted in either increased or decreased cell cycle gene expression. Tumors in which cell cycle gene expression was increased by chemotherapy were likely to be chemotherapy sensitive, whereas tumors in which cell cycle gene transcripts were decreased by chemotherapy were resistant to these agents. A gene expression signature that predicted these changes proved to be a robust and novel index that predicted the response of patients with breast, ovarian, and colon tumors to chemotherapy. Investigations in tumor cell lines supported these findings, and linked treatment induced cell cycle changes with p53 signaling and G1/G0 arrest. Hence, chemotherapy resistance, which can be predicted based on dynamics in cell cycle gene expression, is associated with TP53 integrity. PMID:25749523

  18. Response of the dropped head/bent spine syndrome to treatment with intravenous immunoglobulin.

    PubMed

    Dominick, Justin; Sheean, Geoffrey; Schleimer, Jonathan; Wixom, Christopher

    2006-06-01

    Weakness of neck extension causing a dropped head may result from many neuromuscular disorders. One etiology is isolated neck extensor myopathy. A similar focal myopathy of the lower axial muscles may cause the bent spine syndrome, which manifests as flexion of the trunk and inability to stand upright. Combination of both dropped head and bent spine myopathies is uncommon. Inflammation is usually not pronounced in these conditions and response to immunosuppressive treatment is rare. We present an 81-year-old man who developed progressive weakness of neck and trunk extension over several months, with a prominent inflammatory process in the thoracic paraspinal muscles, which responded dramatically to treatment with intravenous immunoglobulin (IVIg). This case, together with other rare reports, suggests that the presence of inflammation in the biopsy of an affected muscle may predict treatment response.

  19. Testing Equality of Treatments under an Incomplete Block Crossover Design with Ordinal Responses.

    PubMed

    Lui, Kung-Jong

    2017-02-03

    The generalized odds ratio (GOR) for paired sample is considered to measure the relative treatment effect on patient responses in ordinal data. Under a three-treatment two-period incomplete block crossover design, both asymptotic and exact procedures are developed for testing equality between treatments with ordinal responses. Monte Carlo simulation is employed to evaluate and compare the finite-sample performance of these test procedures. A discussion on advantages and disadvantages of the proposed test procedures based on the GOR versus those based on Wald's tests under the normal random effects proportional odds model is provided. The data taken as a part of a crossover trial studying the effects of low and high doses of an analgesic versus a placebo for the relief of pain in primary dysmenorrhea over the first two periods are applied to illustrate the use of these test procedures.

  20. MRI predictors of treatment response for perianal fistulizing Crohn disease in children and young adults.

    PubMed

    Shenoy-Bhangle, Anuradha; Nimkin, Katherine; Goldner, Dana; Bradley, William F; Israel, Esther J; Gee, Michael S

    2014-01-01

    Magnetic resonance imaging (MRI) is considered the imaging standard for diagnosis and characterization of perianal complications associated with Crohn disease in children and adults. To define MRI criteria that could act as potential predictors of treatment response in fistulizing Crohn disease in children, in order to guide more informed study interpretation. We performed a retrospective database query to identify all children and young adults with Crohn disease who underwent serial MRI studies for assessment of perianal symptoms between 2003 and 2010. We examined imaging features of perianal disease including fistula number, type and length, presence and size of associated abscess, and disease response/progression on follow-up MRI. We reviewed imaging studies and electronic medical records. Statistical analysis, including logistic regression, was performed to associate MR imaging features with treatment response and disease progression. We included 36 patients (22 male, 14 female; age range 8-21 years). Of these, 32 had a second MRI exam and 4 had clinical evidence of complete response, obviating the need for repeat imaging. Of the parameters analyzed, presence of abscess, type of fistula according to the Parks classification, and multiplicity were not predictors of treatment outcome. Maximum length of the dominant fistula and aggregate fistula length in the case of multiple fistulae were the best predictors of treatment outcome. Maximum fistula length <2.5 cm was a predictor of treatment response, while aggregate fistula length ≥2.5 cm was a predictor of disease progression. Perianal fistula length is an important imaging feature to assess on MRI of fistulizing Crohn disease.

  1. Differences in maintenance of response upon discontinuation across medication treatments in attention-deficit/hyperactivity disorder.

    PubMed

    Buitelaar, Jan; Asherson, Philip; Soutullo, Cesar; Colla, Michael; Adams, David H; Tanaka, Yoko; Haynes, Virginia S; Escobar, Rodrigo; Upadhyaya, Himanshu

    2015-10-01

    The attention-deficit/hyperactivity disorder (ADHD) treatment literature has been focused on onset-of-effect and short-term effect size, with little exploration of ADHD symptoms upon medication discontinuation. The objective of this narrative review and analysis was to better understand the relapse of ADHD symptoms upon discontinuation of medication treatment in children, adolescents, and adults with ADHD who have responded to medication treatment and to explore differences among different medications in maintaining treatment response. Randomized withdrawal studies of dexmethylphenidate hydrochloride (d-MPH), methylphenidate modified-release (MPH-LA), lisdexamphetamine dimesylate (LDX), guanfacine extended-release (GXR), and atomoxetine (ATX) in both children/adolescents and adults with ADHD were reviewed. The percentage of relapse was significantly higher and the time-to-relapse significantly shorter with placebo compared to active treatment in patients who were previously stable on 5 weeks to 1 year of active treatment, suggesting clinically significant benefit with continued long-term pharmacotherapy. However, percentage of relapse at each time point studied after discontinuing stimulants and GXR appears substantially higher than observed when discontinuing ATX, suggesting longer maintenance of response after discontinuing ATX than after stimulants and GXR. Additionally, slope of relapse percentages over time appears to be more rapid with stimulants or GXR than with ATX. These differences in maintenance of response among ATX, GXR, and stimulants may reflect differences in mechanisms of action and persistence of the medication effect. Alternatively, they may be due to methodological differences, including study design and response/relapse definitions. Continued investigation is needed regarding factors that affect risk of symptom relapse upon discontinuation of pharmacotherapy.

  2. Hyperbaric Oxygen Treatment Induces a Two-Phase Antinociceptive Response of Unusually Long Duration in Mice

    PubMed Central

    Chung, Eunhee; Zelinski, Lisa M.; Ohgami, Yusuke; Shirachi, Donald Y.; Quock, Raymond M.

    2009-01-01

    Hyperbaric oxygen (HBO2) therapy is approved by the FDA for limited clinical indications but is reported to produce pain relief in several chronic pain conditions. However, there have been no studies to explain this apparent analgesic effect of HBO2. Research conducted in our laboratory demonstrates that four daily 60-min HBO2 treatments at 3.5 ATA induced an unparalleled antinociceptive response that consists of 1) an early phase that lasted at least six hours after the HBO2 treatment before dissipating; and 2) a late phase that emerged about 18 hours after the early phase and lasted for up to three weeks. The early phase was sensitive to antagonism by acutely intracerebroventricular (i.c.v.)-administered opioid antagonist naltrexone and the nitric oxide synthase (NOS)-inhibitor L-NAME. The late phase was inhibited by treatment with i.c.v. naltrexone or L-NAME during the four HBO2 treatments but was not antagonized by either naltrexone or L-NAME following acute pretreatment two weeks after HBO2 treatment. These experimental results implicate a novel mechanism that is activated by HBO2, resulting in an antinociceptive response of unusually long duration that is of potential interest in the clinical management of pain. Perspective Hyperbaric oxygen treatment of mice can induce a two-phase antinociceptive response of unusually long duration. Nitric oxide and opioid receptors appear to initiate or mediate both phases of the antinociceptive response. Further elucidation of the underlying mechanism may potentially identify molecular targets that cause long-lasting activation of endogenous analgesic systems. PMID:20418186

  3. Morphological characteristics and HPV genotype predict the treatment response in cutaneous warts.

    PubMed

    Hogendoorn, G K; Bruggink, S C; de Koning, M N C; Eekhof, J A H; Hermans, K E; Rissmann, R; Burggraaf, J; Wolterbeek, R; Quint, K D; Kouwenhoven, S T P; Bavinck, J N B

    2017-06-24

    Cutaneous warts have a cure rate after therapy of no more than approximately 50%. Recently, we developed and validated a standard assessment tool for warts (CWARTS) based on phenotypical characteristics. To assess whether patient and morphological wart characteristics predict the HPV type in the specific wart and whether these characteristics as well as the HPV type predict a favourable treatment response. Photographs were used to score 9 morphological wart characteristics using the newly developed CWARTS tool. Genotyping of 23 wart-associated HPV types was performed using the HSL-PCR/MPG assay. The results were correlated with a favourable response to treatment with monochloroacetic acid, cryotherapy or a combination of cryotherapy and salicylic acid. Odds ratios were calculated using logistic regression in a Generalised Estimating Equations (GEE) model. Black dots (capillary thrombosis) strongly predicted the presence of any HPV type in a wart. From all characteristics tested, the HPV type most strongly predicted the treatment response when the warts were treated with monochloroacetic acid or the combination of cryotherapy and salicylic acid with a significantly decreased treatment response if the warts contained HPVs of the alpha genus (HPV2, HPV27 or HPV 57). When cryotherapy alone was used for common warts, HPV type did not play a role, but cryotherapy was less effective when the wart showed callus and was located deeper in the skin. Morphological characteristics of the warts and the HPV genotype influence treatment outcome and thus potentially influence future treatment decisions for common and plantar warts. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  4. Genetic predictors of the response to the treatment of hepatitis C virus infection

    PubMed Central

    Dzekova-Vidimliski, Pavlina; Nikolov, Igor G.; Matevska-Geshkovska, Nadica; Boyanova, Yana; Nikolova, Nina; Romanciuc, Grigore; Dumitrascu, Dan; Caloska-Ivanova, Viktorija; Joksimovic, Nenad; Antonov, Krasimir; Mateva, Lyudmila; Rostaing, Lionel; Dimovski, Aleksandar; Sikole, Aleksandar

    2015-01-01

    The genome-wide association studies have identified a strong association between interleukin 28B (IL28B) gene polymorphisms and the response to treatment in patients with hepatitis C virus (HCV) infection. The aim of the study was to evaluate the association between three most widely studied IL28B gene polymorphisms and the response to antiviral treatment of chronic hepatitis C. We performed the genotyping of the three IL28B gene polymorphisms: rs12979860, rs8099917, and rs12980275 in 72 Caucasian patients with chronic hepatitis C, previously treated with the combination therapy of pegylated interferon alpha (PEGIFN α) and ribavirin (RBV). The patients included in the study had finished the treatment regimen at least 6 months before enrolling in the study. We used the sustained viral response (SVR) for the evaluation of the effectiveness of the antiviral treatment, and it was tested with an assay with a sensitivity of 20 IU/mL. An SVR was achieved in 59.7% (43/72) of the treated patients. The three IL28B gene polymorphisms (CC genotype of rs12979860, TT genotype of rs8099917, and AA genotype of rs12980275) were associated with the SVR (p = 0.029, p = 0.016, and p = 0.028, respectively) in the study patients with chronic hepatitis C treated with the combination therapy of PEGIFN α and RBV. The association of IL28B gene polymorphisms with the treatment response points to the possibility of personalized medicine for the treatment of HCV infection. PMID:26614853

  5. Response to long-term enzyme replacement treatment in dogs with exocrine pancreatic insufficiency.

    PubMed

    Wiberg, M E; Lautala, H M; Westermarck, E

    1998-07-01

    To study response to long-term enzyme replacement treatment in dogs with exocrine pancreatic insufficiency (EPI). Cross-sectional study. 76 German Shepherd Dogs or rough-coated Collies with EPI and 145 clinically normal dogs of the same breeds. Questionnaires were sent to owners of dogs with EPI and owners of clinically normal dogs. Dogs with EPI had been given dietary enzyme supplements for at least 4 months. Relative frequency distributions of gastrointestinal tract and dermatologic signs, prevalences of typical signs of EPI (e.g., weight loss, ravenous appetite, yellow and pulpy feces, high fecal volume), feeding regimens, and dietary intolerances were compared between dogs with EPI and clinically normal dogs. Gastrointestinal tract signs considered typical for dogs with EPI were almost completely controlled with dietary enzyme supplements in half of the dogs with EPI, and their general health was similar to that of clinically normal dogs. A poor treatment response was found in a fifth of dogs with EPI that had several signs that were typical of EPI. Signs most often persisting were high fecal volume, yellow and pulpy feces, and flatulence. Dermatologic problems were common, especially in German Shepherd Dogs with EPI. Treatment response was irrespective of breed. Nonenteric-coated enzyme supplements, powdered enzyme, and raw chopped pancreas were equally effective in controlling clinical signs. Although dietary sensitivities were common, use of adjunctive dietary treatment was minimal. Antibiotics were occasionally administered to half of the dogs with EPI. Results of this study indicate that, with basically similar treatment regimens, response to long-term enzyme treatment in dogs with EPI varied considerably.

  6. Race, genetic ancestry and response to antidepressant treatment for major depression.

    PubMed

    Murphy, Eleanor; Hou, Liping; Maher, Brion S; Woldehawariat, Girma; Kassem, Layla; Akula, Nirmala; Laje, Gonzalo; McMahon, Francis J

    2013-12-01

    The Sequenced Treatment Alternatives to Relieve Depression (STAR*D) Study revealed poorer antidepressant treatment response among black compared with white participants. This racial disparity persisted even after socioeconomic and baseline clinical factors were taken into account. Some studies have suggested genetic contributions to this disparity, but none have attempted to disentangle race and genetic ancestry. Here we used genome-wide single-nucleotide polymorphism (SNP) data to examine independent contributions of race and genetic ancestry to citalopram response. Secondary data analyses included 1877 STAR*D participants who completed an average of 10 weeks of citalopram treatment and provided DNA samples. Participants reported their race as White (n=1464), black (n=299) or other/mixed (n=114). Genetic ancestry was estimated by multidimensional scaling (MDS) analyses of about 500 000 SNPs. Ancestry proportions were estimated by STRUCTURE. Structural equation modeling was used to examine the direct and indirect effects of observed and latent predictors of response, defined as change in the Quick Inventory of Depressive Symptomatology (QIDS) score from baseline to exit. Socioeconomic and baseline clinical factors, race, and anxiety significantly predicted response, as previously reported. However, direct effects of race disappeared in all models that included genetic ancestry. Genetic African ancestry predicted lower treatment response in all models. Although socioeconomic and baseline clinical factors drive racial differences in antidepressant response, genetic ancestry, rather than self-reported race, explains a significant fraction of the residual differences. Larger samples would be needed to identify the specific genetic mechanisms that may be involved, but these findings underscore the importance of including more African-American patients in drug trials.

  7. Relationship between response to colchicine treatment and MDR1 polymorphism in familial Mediterranean fever patients.

    PubMed

    Uludag, Ahmet; Silan, Coskun; Atik, Sinem; Akurut, Cisem; Uludag, Aysegul; Silan, Fatma; Ozdemir, Ozturk

    2014-02-01

    Investigate the relationship between MDR1 C3435T polymorphism and colchicine response in Familial Mediterranean fever (FMF) patients. Patients (n=50) who received colchicine regularly, were willing to participate in the study, and attended control visits were included in the study. MDR1 C3435T genotype was defined by the real-time polymerase chain reaction method. Patients were divided into three groups. Patients, who recovered from episodes with standard colchicine treatment, and had no attack in the last 1 year were accepted as complete; patients whose episode number and intensity were decreased with the ongoing standard treatment as partial; and patients whose episodes were not decreased despite the standard treatment as nonresponders. MDR1 C and T allele frequencies of FMF patients with colchicine responses of complete, partial, and nonresponders were C=0.75 and T=0.25; C=0.56 and T=0.44; and C=0.50 and T=0.50, respectively. When complete responding patients were compared with the partial responding patients, subjects with CT genotype had 6.18 times more increased risk than with CC genotype (OR=6.18; p=0.015). Poor response risk of subjects with the T allele was increased 2.45 times more when compared with the C allele (p=0.03). MDR1 gene C3435T polymorphism enacts an important role on colchicine response in FMF; good response to colchicine treatment was related to the C allele, whereas poor response was related to the T allele in FMF.

  8. The Treatment Responses in Cases of Radiation Therapy to Portal Vein Thrombosis in Advanced Hepatocellular Carcinoma

    SciTech Connect

    Huang, Y.-J.; Hsu, H.-C.; Wang, C.-Y.; Wang, C.-J.; Chen, H.-C.; Huang, E.-Y.; Fang, F.-M.; Lu, S.-N.

    2009-03-15

    Purpose: To review the response to radiation therapy for hepatocellular carcinoma (HCC) with portal vein thrombosis (PVT) and determine the factors favoring its efficacy. Methods and Materials: Patients with HCC and PVT referred for radiation therapy between 1997 and 2005 were retrospectively reviewed. Patients who had undergone treatment to primary HCC before radiation or had extrahepatic metastasis were excluded. A radiation dose of 60 Gy with 2 to 3Gy per fraction was prescribed. Clinical features before therapy were investigated, and the most significant imaging change after radiotherapy was regarded as the treatment response. Survival times were compared and the hazard ratios of independent variables were determined. Results: The treatment response rate of the 326 patients included in the study was 25.2% (n = 82). The median survival times were 13.3, 11.6, 9.0, 4.5, and 2.1 months for complete response, partial response, vascular transformation, no response, and the lost follow-up patients, respectively. Statistically significant differences in survival were not found among responder groups (p = 0.224-0.916) but were found between responders and nonresponders (p = 0.002). The most significant independent variables associated with survival (p < 0.001) were performance status and radiation dose. Minor independent factors were ascites, alfa-fetoprotein, albumin, and HBsAg (p = 0.009-0.038). In patients with favorable performance status, those with no more than one minor risk factor had a superior prognosis after radiation therapy (p = 0.013). This result was verified by a review of similar patients in 2006. Conclusion: Radiation therapy is the treatment of choice for selected HCC patients with PVT.

  9. A responsive evaluation of mental health treatment in Cambodia: Intentionally addressing poverty to increase cultural responsiveness in therapy.

    PubMed

    Seponski, Desiree M; Lewis, Denise C; Megginson, Maegan C

    2014-01-01

    Mental health issues are significant contributors to the global burden of disease with the highest incidence in resource poor countries; 90% of those in need of mental health treatment reside in low resource countries but receive only 10% of the world's resources. Cambodia, the eighth least developed country in the world, serves as one example of the need to address mental health concerns in low-income, resource poor countries. The current study utilises responsive evaluation methodology to explore how poverty-stricken Cambodian clients, therapists and supervisors experience Western models of therapy as culturally responsive to their unique needs. Quantitative and qualitative data were triangulated across multiple stakeholders using numerous methods including a focus group, interviews, surveys, case illustrations and live supervision observation and analysed using constant comparative analysis. Emerging findings suggest that poverty, material needs, therapy location and financial situations greatly impact the daily lives and mental health conditions of Cambodians and hinder clients' therapeutic progress. The local community needs and context of poverty greatly hinder clients' therapeutic progress in therapy treatment and when therapy does not directly address the culture of poverty, clients did not experience therapy as valuable despite some temporary decreases in mental health symptoms.

  10. Long-Range Temporal Correlations Reflect Treatment Response in the Electroencephalogram of Patients with Infantile Spasms.

    PubMed

    Smith, Rachel J; Sugijoto, Amanda; Rismanchi, Neggy; Hussain, Shaun A; Shrey, Daniel W; Lopour, Beth A

    2017-09-13

    Infantile spasms syndrome is an epileptic encephalopathy in which prompt diagnosis and treatment initiation are critical to therapeutic response. Diagnosis of the disease heavily depends on the identification of characteristic electroencephalographic (EEG) patterns, including hypsarrhythmia. However, visual assessment of the presence and characteristics of hypsarrhythmia is challenging because multiple variants of the pattern exist, leading to poor inter-rater reliability. We investigated whether a quantitative measurement of the control of neural synchrony in the EEGs of infantile spasms patients could be used to reliably distinguish the presence of hypsarrhythmia and indicate successful treatment outcomes. We used autocorrelation and Detrended Fluctuation Analysis (DFA) to measure the strength of long-range temporal correlations in 21 infantile spasms patients before and after treatment and 21 control subjects. The strength of long-range temporal correlations was significantly lower in patients with hypsarrhythmia than control patients, indicating decreased control of neural synchrony. There was no difference between patients without hypsarrhythmia and control patients. Further, the presence of hypsarrhythmia could be classified based on the DFA exponent and intercept with 92% accuracy using a support vector machine. Successful treatment was marked by a larger increase in the DFA exponent compared to those in which spasms persisted. These results suggest that the strength of long-range temporal correlations is a marker of pathological cortical activity that correlates with treatment response. Combined with current clinical measures, this quantitative tool has the potential to aid objective identification of hypsarrhythmia and assessment of treatment efficacy to inform clinical decision-making.

  11. Plasma Progesterone Concentrations in Dairy Cows with Cystic Ovaries and Clinical Responses Following Treatment with Fenprostalene

    PubMed Central

    Leslie, K. E.; Bosu, W. T. K.

    1983-01-01

    Sixty-two dairy cows diagnosed as having cystic ovarian degeneration were used to study the correlation between rectal palpation findings and plasma progesterone concentrations and the response of cysts to treatment using fenprostalene, a luteolytic agent. Rectal palpation accurately determined the presence of luteal cysts as confirmed by plasma progesterone concentrations of 3 ng/mL or more. Treatment with fenprostalene was very effective for luteal cysts: a high percentage of treated cows exhibited estrus within seven days after treatment. The conception rate following artifical insemination during the induced estrus was 87.5% (21/24). Rectal palpation was much less accurate for the diagnosis of follicular cysts. Cows diagnosed as having follicular cysts had wide variations in plasma progesterone concentrations. Response to fenprostalene treatment was poor in cows with nonluteinized cystic follicles associated with low progesterone concentrations. However, cows diagnosed as having follicular cysts, but with progesterone concentrations of 1 ng/mL or more, responded better to fenprostalene treatment than cows with low progesterone concentrations. It was concluded that, if correctly diagnosed, luteal cysts can be successfully treated with fenprostalene, and conception rates following treatment can be expected to be normal. PMID:17422330

  12. Avian community responses to juniper woodland structure and thinning treatments on the Colorado Plateau

    USGS Publications Warehouse

    Crow, Claire; van Riper, Charles

    2011-01-01

    We also studied responses of breeding birds to mechanical reduction of pinyon-juniper woodlands scattered across sagebrush steppe in 11 control and 9 treatment plots at Grand Staircase-Escalante National Monument, Utah, in 2005 and 2006. We surveyed birds in 3.1-ha (7.6-acre) plots during the breeding season before and following treatment. Thinning in April 2006 removed a mean of 92 percent (standard error = 6.4 percent) of the live trees from treatment plots. Two of 14 species, Gray Vireo (Vireo vicinior) and Brown-headed Cowbird (Molothrus ater), were not detected after thinning. Shrub-nesting birds, including sagebrush specialist Brewer's Sparrow (Spizella breweri), increased in relative abundance in treatment areas compared to controls. However, some species may exhibit a time lag in response, and further changes in community composition and abundance could result. Our findings lend support to the concept that multiple small-scale fuels-reduction treatments, applied over the landscape, may provide the variety of successional stages needed to support a full assemblage of avian species in pinyon-juniper woodlands on the Colorado Plateau. Limiting scale and increasing precision of fuels-reduction projects in pinyon-juniper vegetation communities may maximize the benefits of management to both the pinyon-juniper and sagebrush steppe avian communities. We conclude that small-scale fuels-reduction treatments can benefit many bird species while reducing fire risk and restoring an ecological balance.

  13. Short-term and long-term response to pulmonary exacerbation treatment in cystic fibrosis.

    PubMed

    Heltshe, Sonya L; Goss, Christopher H; Thompson, Valeria; Sagel, Scott D; Sanders, Don B; Marshall, Bruce C; Flume, Patrick A

    2016-03-01

    Treatment of pulmonary exacerbations (PEx) in cystic fibrosis (CF) varies widely with no consensus on management practices or best indicators of therapeutic success. To design trials evaluating PEx treatment factors, we characterise the heterogeneity of PEx care in adults and paediatrics, and correlate it with measures of clinical response including short-term and long-term lung function changes, change in symptom severity score and time to next intravenous antibiotic therapy. Data were used from a prospective observational study of patients with CF ≥10 years of age enrolled at six sites between 2007 and 2010. All were started on intravenous antibiotics for a clinically diagnosed PEx. Analysis of variance, logistic and Cox regression were used to examine the association of treatment factors with short-term and long-term clinical response. Of 123 patients with CF (60% women, aged 23.1±10.2 years), 33% experienced <10% relative improvement in FEV1 during treatment, which was associated with failing to recover baseline lung function 3 months after treatment (OR=7.8, 95% CI 1.9 to 31.6, p=0.004) and a longer time to next intravenous antibiotic (HR=0.48, 95% CI 0.27 to 0.85, p=0.011). Symptom improvement was observed but was not associated with subsequent lung function or time to next antibiotic therapy, which had a median recurrence time of 143 days. Immediate symptomatic or respiratory response to PEx treatment did not have a clear relationship with subsequent outcomes such as lung function or intravenous antibiotic-free interval. These results can inform future research of treatment regimens for PEx in terms of interventions and outcome measures. NCT00788359 (www.clinicaltrials.gov). 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/

  14. The impact of melanoma genetics on treatment response and resistance in clinical and experimental studies.

    PubMed

    Kunz, M; Hölzel, M

    2017-02-16

    Recent attempts to characterize the melanoma mutational landscape using high-throughput sequencing technologies have identified new genes and pathways involved in the molecular pathogenesis of melanoma. Apart from mutated BRAF, NRAS, and KIT, a series of new recurrently mutated candidate genes with impact on signaling pathways have been identified such as NF1, PTEN, IDH1, RAC1, ARID2, and TP53. Under targeted treatment using BRAF and MEK1/2 inhibitors either alone or in combination, a majority of patients experience recurrences, which are due to different genetic mechanisms such as gene amplifications of BRAF or NRAS, MEK1/2 and PI3K mutations. In principle, resistance mechanisms converge on two signaling pathways, MAPK and PI3K-AKT-mTOR pathways. Resistance may be due to small subsets of resistant cells within a heterogeneous tumor mass not identified by sequencing of the bulk tumor. Future sequencing studies addressing tumor heterogeneity, e.g., by using single-cell sequencing technology, will most likely improve this situation. Gene expression patterns of metastatic lesions were also shown to predict treatment response, e.g., a MITF-low/NF-κB-high melanoma phenotype is resistant against classical targeted therapies. Finally, more recent treatment approaches using checkpoint inhibitors directed against PD-1 and CTLA-4 are very effective in melanoma and other tumor entities. Here, the mutational and neoantigen load of melanoma lesions may help to predict treatment response. Taken together, the new sequencing, molecular, and bioinformatic technologies exploiting the melanoma genome for treatment decisions have significantly improved our understanding of melanoma pathogenesis, treatment response, and resistance for either targeted treatment or immune checkpoint blockade.

  15. Targeted Proteomics to Assess the Response to Anti-Angiogenic Treatment in Human Glioblastoma (GBM).

    PubMed

    Demeure, Kevin; Fack, Fred; Duriez, Elodie; Tiemann, Katja; Bernard, Amandine; Golebiewska, Anna; Bougnaud, Sébastien; Bjerkvig, Rolf; Domon, Bruno; Niclou, Simone P

    2016-02-01

    Glioblastoma (GBM) is a highly aggressive primary brain tumor with dismal outcome for affected patients. Because of the significant neo-angiogenesis exhibited by GBMs, anti-angiogenic therapies have been intensively evaluated during the past years. Recent clinical studies were however disappointing, although a subpopulation of patients may benefit from such treatment. We have previously shown that anti-angiogenic targeting in GBM increases hypoxia and leads to a metabolic adaptation toward glycolysis, suggesting that combination treatments also targeting the glycolytic phenotype may be effective in GBM patients. The aim of this study was to identify marker proteins that are altered by treatment and may serve as a short term readout of anti-angiogenic therapy. Ultimately such proteins could be tested as markers of efficacy able to identify patient subpopulations responsive to the treatment. We applied a proteomics approach based on selected reaction monitoring (SRM) to precisely quantify targeted protein candidates, selected from pathways related to metabolism, apoptosis and angiogenesis. The workflow was developed in the context of patient-derived intracranial GBM xenografts developed in rodents and ensured the specific identification of human tumor versus rodent stroma-derived proteins. Quality control experiments were applied to assess sample heterogeneity and reproducibility of SRM assays at different levels. The data demonstrate that tumor specific proteins can be precisely quantified within complex biological samples, reliably identifying small concentration differences induced by the treatment. In line with previous work, we identified decreased levels of TCA cycle enzymes, including isocitrate dehydrogenase, whereas malectin, calnexin, and lactate dehydrogenase A were augmented after treatment. We propose the most responsive proteins of our subset as potential novel biomarkers to assess treatment response after anti-angiogenic therapy that warrant future

  16. The role of readiness to change in response to treatment of adolescent depression.

    PubMed

    Lewis, Cara C; Simons, Anne D; Silva, Susan G; Rohde, Paul; Small, David M; Murakami, Jessica L; High, Robin R; March, John S

    2009-06-01

    The effect of readiness to change on treatment outcome was examined among 332 adolescents (46% male, 74% Caucasian), ages 12 through 17 years (M = 14.6, SD = 1.5), with major depressive disorder who were participating in the Treatment for Adolescents With Depression Study (TADS). TADS is a randomized clinical trial comparing the effectiveness of fluoxetine (an antidepressant medication), cognitive-behavioral therapy, their combination, and a pill placebo. An abbreviated Stages of Change Questionnaire was used to obtain 4 readiness to change scores: precontemplation, contemplation, action, and maintenance. The association between each readiness score and depression severity across 12 weeks of acute treatment for depression, as measured by the Children's Depression Rating Scale--Revised, was examined. Although treatment response was not moderated by any of the readiness scores, baseline action scores predicted outcome: Higher action scores were associated with better outcome regardless of treatment modality. Furthermore, treatment effects were mediated by change in action scores during the first 6 weeks of treatment, with increases in action scores related to greater improvement in depression. Assessing readiness to change may have implications for tailoring treatments for depressed adolescents.

  17. Assessment and monitoring of treatment response in adult ADHD patients: current perspectives

    PubMed Central

    Ramsay, J Russell

    2017-01-01

    Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental syndrome that emerges in childhood or early adolescence and persists into adulthood for a majority of individuals. There are many other adults with ADHD who may not seek out evaluation and treatment until adulthood, having been able to “get by” before struggling with inattention, hyperactivity, and/or impulsivity in adulthood, in addition to facing the associated features of disorganization, poor time management, and procrastination among many others. A lifetime diagnosis of ADHD is associated with a wide range of life impairments, which makes a comprehensive and accurate diagnostic assessment essential in order to obtain appropriate treatment. Moreover, while there are effective medical and psychosocial treatments for ADHD, it is important to be able to track treatment response in order to evaluate whether adjustments in specific interventions are needed or referrals for adjunctive treatments and supports are indicated to facilitate optimal therapeutic outcomes. The goal of this article is to provide a clinically useful review of the various measures that practicing clinicians can use to aid in the diagnostic assessment and monitoring of psychosocial and medical treatment of ADHD in adult patients. This review includes various structured interviews, screening scales, adult ADHD symptom inventories, measures of associated features of ADHD, as well as ratings of impairment and functioning which can be adapted to clinicians’ practice needs in order to track treatment progress and optimize treatments for adults with ADHD. PMID:28184164

  18. Weight Gain and Response to Treatment for Multidrug-Resistant Tuberculosis

    PubMed Central

    Gler, Ma Tarcela; Guilatco, Ruffy; Caoili, Janice C.; Ershova, Julia; Cegielski, Peter; Johnson, John L.

    2013-01-01

    Alternatives to culture are needed in high burden countries to assess whether response to treatment of multidrug-resistant-tuberculosis (MDR-TB) is satisfactory. The objective was to assess the association of weight gain and treatment outcome. The methods included analysis of clinical, bacteriologic, and weight from 439 MDR-TB patients in the Philippines. Odds ratios (ORs) were calculated to determine whether 5% weight gain during the first 6 months of treatment was associated with outcome. Three hundred and ten (71%) patients were cured and 129 (29%) had poor outcomes (death, defaulted, or failed treatment). Fifty-three percent were underweight (body mass index [BMI] < 18.5 kg/m2) before treatment. Five percent weight gain after completing 3 months of treatment was associated with good outcome among patients who were underweight before treatment (OR 2.1; 95% confidence interval [CI], 1.05 to 4.4). Baseline weight and degree of weight change during the first 6 months of treatment can help identify persons who are more likely to have poor outcomes and require other interventions. PMID:24019430

  19. PET-Based Treatment Response Evaluation in Rectal Cancer: Prediction and Validation

    SciTech Connect

    Janssen, Marco H.M.; Oellers, Michel C.; Stiphout, Ruud G.P.M. van; Riedl, Robert G.; Bogaard, Jorgen van den; Buijsen, Jeroen; Lambin, Philippe; Lammering, Guido

    2012-02-01

    Purpose: To develop a positron emission tomography (PET)-based response prediction model to differentiate pathological responders from nonresponders. The predictive strength of the model was validated in a second patient group, treated and imaged identical to the patients on which the predictive model was based. Methods and Materials: Fifty-one rectal cancer patients were prospectively included in this study. All patients underwent fluorodeoxyglucose (FDG) PET-computed tomography (CT) imaging both before the start of chemoradiotherapy (CRT) and after 2 weeks of treatment. Preoperative treatment with CRT was followed by a total mesorectal excision. From the resected specimen, the tumor regression grade (TRG) was scored according to the Mandard criteria. From one patient group (n = 30), the metabolic treatment response was correlated with the pathological treatment response, resulting in a receiver operating characteristic (ROC) curve based cutoff value for the reduction of maximum standardized uptake value (SUV{sub max}) within the tumor to differentiate pathological responders (TRG 1-2) from nonresponders (TRG 3-5). The applicability of the selected cutoff value for new patients was validated in a second patient group (n = 21). Results: When correlating the metabolic and pathological treatment response for the first patient group using ROC curve analysis (area under the curve = 0.98), a cutoff value of 48% SUV{sub max} reduction was selected to differentiate pathological responders from nonresponders (specificity of 100%, sensitivity of 64%). Applying this cutoff value to the second patient group resulted in a specificity and sensitivity of, respectively, 93% and 83%, with only one of the pathological nonresponders being false positively predicted as pathological responding. Conclusions: For rectal cancer, an accurate PET-based prediction of the pathological treatment response is feasible already after 2 weeks of CRT. The presented predictive model could be used to

  20. The Insomnia Severity Index: Psychometric Indicators to Detect Insomnia Cases and Evaluate Treatment Response

    PubMed Central

    Morin, Charles M.; Belleville, Geneviève; Bélanger, Lynda; Ivers, Hans

    2011-01-01

    Background: Although insomnia is a prevalent complaint with significant morbidity, it often remains unrecognized and untreated. Brief and valid instruments are needed both for screening and outcome assessment. This study examined psychometric indices of the Insomnia Severity Index (ISI) to detect cases of insomnia in a population-based sample and to evaluate treatment response in a clinical sample. Methods: Participants were 959 individuals selected from the community for an epidemiological study of insomnia (Community sample) and 183 individuals evaluated for insomnia treatment and 62 controls without insomnia (Clinical sample). They completed the ISI and several measures of sleep quality, fatigue, psychological symptoms, and quality of life; those in the Clinical sample also completed sleep diaries, polysomnography, and interviews to validate their insomnia/good sleep status and assess treatment response. In addition to standard psychometric indices of reliability and validity, item response theory analyses were computed to examine ISI item response patterns. Receiver operating curves were used to derive optimal cutoff scores for case identification and to quantify the minimally important changes in relation to global improvement ratings obtained by an independent assessor. Results: ISI internal consistency was excellent for both samples (Cronbach α of 0.90 and 0.91). Item response analyses revealed adequate discriminatory capacity for 5 of the 7 items. Convergent validity was supported by significant correlations between total ISI score and measures of fatigue, quality of life, anxiety, and depression. A cutoff score of 10 was optimal (86.1% sensitivity and 87.7% specificity) for detecting insomnia cases in the community sample. In the clinical sample, a change score of −8.4 points (95% CI: −7.1, −9.4) was associated with moderate improvement as rated by an independent assessor after treatment. Conclusion: These findings provide further evidence that the

  1. Pregabalin for the treatment of patients with generalized anxiety disorder with inadequate treatment response to antidepressants and severe depressive symptoms.

    PubMed

    Olivares, José M; Álvarez, Enrique; Carrasco, José L; Pérez Páramo, María; López-Gómez, Vanessa

    2015-09-01

    To evaluate the effectiveness of pregabalin in patients with resistant generalized anxiety disorder (GAD) and severe depressive symptoms, we carried out a post-hoc analysis of a multicenter, prospective, and observational 6-month study. We included patients who were at least 18 years old, fulfilled the Diagnostic and Statistical Manual of Mental Disorders, 4th ed. (DSM-IV) criteria for GAD, showed inadequate responses to previous courses of antidepressant treatment, had Montgomery-Asberg Rating Scale scores of at least 35, had not received pregabalin previously, and were prescribed pregabalin upon entry into this study. We included 1815 patients fulfilling the DSM-IV criteria for GAD, and 133 (7.3%) fulfilled the selection criteria for these analyses. Ninety-seven percent of the patients received pregabalin (mean dose: 222 mg/day) in combination with other psychotropics. The Hamilton Anxiety Scale total score was reduced by a mean of 20.3 points (95% confidence interval, 22.1-18.4) (57.2% reduction) at month 6. Pregabalin also ameliorated comorbid depressive symptoms, with a reduction in the mean score of the Montgomery-Asberg Rating Scale of 22.3 points (95% confidence interval, 24.2-20.4) (56.6% reduction). Our results suggest that pregabalin, as part of a combination regimen with antidepressants and/or benzodiazepines, might be effective for the treatment of patients with GAD who have shown inadequate response to previous antidepressants and have severe depressive symptoms.

  2. Diencephalic serotonin transporter availability predicts both transporter occupancy and treatment response to sertraline in obsessive-compulsive checkers.

    PubMed

    Zitterl, Werner; Stompe, Thomas; Aigner, Martin; Zitterl-Eglseer, Karin; Ritter, Kristina; Zettinig, Georg; Hornik, Kurt; Asenbaum, Susanne; Pirker, Walter; Thau, Kenneth

    2009-12-15

    To our knowledge, no studies have investigated the predictive value of central serotonin transporter (SERT) availability for treatment response to serotonin reuptake inhibitors (SSRIs) in patients with obsessive-compulsive disorder (OCD). This study used brain imaging to examine the relationship between pretreatment SERT availability and transporter occupancy as well as treatment response by sertraline in patients displaying prominent behavioral checking compulsions (OC checkers). Single photon emission computed tomography (SPECT) was used to measure thalamic-hypothalamic SERT availability with [(123)I]-2beta-carbomethoxy-3beta-(4-iodophenyl)-tropane in 28 nondepressed OC checkers at baseline and after 14 weeks of treatment with sertraline (175 mg daily). SERT availability was correlated with OC severity and treatment response as assessed with the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS). Associations between individual transporter occupancies and clinical parameters were investigated. 1) Correlation analyses between thalamic-hypothalamic SERT availability and OC severity showed significant negative associations at baseline and after treatment with sertraline. 2) Pretreatment SERT availability correlated significantly with both transporter occupancy and treatment response; in addition, a positive association was found between transporter occupancy and treatment response directly. 3) Using multivariate statistical models, the data demonstrated that higher pretreatment SERT availability significantly predicted higher occupancy rates as well as better treatment response 14 weeks later. Higher pretreatment thalamic-hypothalamic SERT availability may predict both higher occupancy rates and better treatment response to sertraline. The data suggest a strong connection between transporter occupancy and treatment response.

  3. Higher order response adaptive urn designs for clinical trials with highly successful treatments

    PubMed Central

    Ivanova, Anastasia; Hoberman, Steven

    2014-01-01

    Summary We consider a problem of reducing the expected number of treatment failures in trials where the probability of response to treatment is close to 1 and treatments are compared based on log odds ratio. We propose a new class of urn designs for randomization of patients in a clinical trial. The new urn designs target a number of allocation proportions including the allocation proportion that yields the same power as equal allocation but significantly less expected treatment failures. The new design is compared with the doubly adaptively biased coin design, the efficient randomized adaptive design and with equal allocation. The properties of the new class of designs are studied by embedding them into a family of continuous time stochastic processes. PMID:25641991

  4. Pivotal Response Treatment Parent Training for Autism: Findings from a 3-Month Follow-Up Evaluation.

    PubMed

    Gengoux, Grace W; Berquist, Kari L; Salzman, Emma; Schapp, Salena; Phillips, Jennifer M; Frazier, Thomas W; Minjarez, Mendy B; Hardan, Antonio Y

    2015-09-01

    This study's objective was to assess maintenance of treatment effects 3 months after completion of a 12-week Pivotal Response Treatment (PRT) parent education group. Families who completed the active treatment (N = 23) were followed for an additional 12 weeks to measure changes in language and cognitive skills. Results indicated a significant improvement in frequency of functional utterances, with maintenance at 3-month follow-up [F(2, 21): 5.9, p = .009]. Children also made significant gains on the Vineland Communication Domain Standard Score [F(2, 12):11.74, p = .001] and the Mullen Scales of Early Learning Composite score [F(1, 20) = 5.43, p = .03]. These results suggest that a brief PRT parent group intervention can lead to improvements in language and cognitive functioning that are maintained 12 weeks post treatment.

  5. Response-Guided Telaprevir Combination Treatment for Hepatitis C Virus Infection

    PubMed Central

    Sherman, Kenneth E.; Flamm, Steven L.; Afdhal, Nezam H.; Nelson, David R.; Sulkowski, Mark S.; Everson, Gregory T.; Fried, Michael W.; Adler, Michael; Reesink, Hendrik W.; Martin, Marie; Sankoh, Abdul J.; Adda, Nathalie; Kauffman, Robert S.; George, Shelley; Wright, Christopher I.; Poordad, Fred

    2013-01-01

    BACKGROUND Patients with chronic infection with hepatitis C virus (HCV) genotype 1 often need 48 weeks of peginterferon–ribavirin treatment for a sustained virologic response. We designed a noninferiority trial (noninferiority margin, −10.5%) to compare rates of sustained virologic response among patients receiving two treatment durations. METHODS We enrolled patients with chronic infection with HCV genotype 1 who had not previously received treatment. All patients received telaprevir at a dose of 750 mg every 8 hours, peginterferon alfa-2a at a dose of 180 μg per week, and ribavirin at a dose of 1000 to 1200 mg per day, for 12 weeks (T12PR12), followed by peginterferon–ribavirin. Patients who had an extended rapid virologic response (undetectable HCV RNA levels at weeks 4 and 12) were randomly assigned after week 20 to receive the dual therapy for 4 more weeks (T12PR24) or 28 more weeks (T12PR48). Patients without an extended rapid virologic response were assigned to T12PR48. RESULTS Of the 540 patients, a total of 352 (65%) had an extended rapid virologic response. The overall rate of sustained virologic response was 72%. Among the 322 patients with an extended rapid virologic response who were randomly assigned to a study group, 149 (92%) in the T12PR24 group and 140 (88%) in the T12PR48 group had a sustained virologic response (absolute difference, 4 percentage points; 95% confidence interval, −2 to 11), establishing noninferiority. Adverse events included rash (in 37% of patients, severe in 5%) and anemia (in 39%, severe in 6%). Discontinuation of all the study drugs was based on adverse events in 18% of patients overall, as well as in 1% of patients (all of whom were randomly assigned) in the T12PR24 group and 12% of the patients randomly assigned to the T12PR48 group (P<0.001). CONCLUSIONS In this study, among patients with chronic HCV infection who had not received treatment previously, a regimen of peginterferon–ribavirin for 24 weeks, with

  6. Does a family history of RA influence the clinical presentation and treatment response in RA?

    PubMed

    Frisell, Thomas; Saevarsdottir, Saedis; Askling, Johan

    2016-06-01

    To assess whether family history of rheumatoid arthritis (RA), among the strongest risk factors for developing RA, also carries information on the clinical presentation and treatment response. The prospective Swedish Rheumatology register was linked to family history of RA, defined as diagnosed RA in any first-degree relative, ascertained through the Swedish Multi-Generation and Patient registers. Clinical presentation was examined among patients with early RA 2000-2011 (symptom onset <12 months before inclusion, N=6869), and response to methotrexate (MTX) monotherapy in the subset starting this treatment (N=4630). Response to tumour necrosis factor inhibitors (TNFi) was examined among all patients with RA starting a TNFi as the first biological disease-modifying antirheumatic drug 2000-2011 (N=9249). Association of family history with clinical characteristics, drug survival, European League Against Rheumatism (EULAR) response and change in disease activity at 3 and 6 months was estimated using linear and generalised logistic regression models. Correlation in relatives' response measures was also assessed. Patients with early RA with family history of RA were more often rheumatoid factor positive, but with no other clinically meaningful differences in their clinical presentation. Family history of RA did not predict response to MTX or TNFi, with the possible exception of no versus good EULAR response to TNFi at 6 months (OR=1.4, 95% CI 1.1 to 1.7). Having a relative who discontinued TNFi within a year increased the odds of doing the same (OR=3.7, 95% CI 1.8 to 7.5), although we found no significant familial correlations in change in disease activity measures. Family history of RA did not modify the clinical presentation of RA or predict response to standard treatment with MTX or TNFi. Treatment response, particularly drug survival, may itself be familial. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a

  7. Treatment of cockroach allergen asthma model with imatinib attenuates airway responses.

    PubMed

    Berlin, Aaron A; Lukacs, Nicholas W

    2005-01-01

    In the present study it was determined whether a pharmacologic approach to blocking receptor tyrosine kinase-mediated activation during allergic airway responses could be beneficial. To examine these responses, allergic mice were given a single oral dose of imatinib at clinically relevant concentrations, ranging from 0.05 to 50 mg/kg, by oral gavages just before allergen challenge. The reduction in the allergen-induced responses was significant and centered on reducing overall inflammation as well as pulmonary cytokine levels. In particular, the treatment of the mice with imatinib significantly attenuated airway hyperreactivity and peribronchial eosinophil accumulation, and significantly reduced Th2 cytokines, interleukin-4 and interleukin-13. In addition, chemokines previously associated with allergen-induced pulmonary disease, CCL2, CCL5, and CCL6, were significantly reduced in the lungs of the imatinib-treated animals. Together these data demonstrate that the pharmacologic inhibitor imatinib may provide a clinically attractive therapy for allergic, asthmatic responses.

  8. Age and sex differences in immune response following LPS treatment in mice.

    PubMed

    Cai, Kyle Chiman; van Mil, Spencer; Murray, Emma; Mallet, Jean-François; Matar, Chantal; Ismail, Nafissa

    2016-11-01

    Puberty is an important developmental event that is marked by the reorganizing and remodeling of the brain. Exposure to stress during this critical period of development can have enduring effects on both reproductive and non-reproductive behaviors. The purpose of this study was to investigate age and sex differences in immune response by examining sickness behavior, body temperature changes, and serum cytokine levels following an immune challenge. The effects of circulating gonadal hormones on age and sex differences in immune response were also examined. Results showed that male mice display more sickness behavior and greater fluctuations in body temperature following LPS treatment than female mice. Moreover, adult male mice display more sickness behavior and a greater drop in body temperature following LPS treatment compared to pubertal male mice. Following gonadectomy, pubertal and adult males displayed steeper and prolonged drops in body temperature compared to sham-operated counterparts. Gonadectomy did not eliminate sex differences in LPS-induced body temperature changes, suggesting that additional factors contribute to the observed differences. LPS treatment increased cytokine levels in all mice. However, the increase in pro-inflammatory cytokines was higher in adult compared to pubertal mice, while the increase in anti-inflammatory cytokines was greater in pubertal than in adult mice. Our findings contribute to a better understanding of age and sex differences in acute immune response following LPS treatment and possible mechanisms involved in the enduring alterations in behavior and brain function following pubertal exposure to LPS.

  9. Neurobiological markers predicting treatment response in anxiety disorders: A systematic review and implications for clinical application.

    PubMed

    Lueken, Ulrike; Zierhut, Kathrin C; Hahn, Tim; Straube, Benjamin; Kircher, Tilo; Reif, Andreas; Richter, Jan; Hamm, Alfons; Wittchen, Hans-Ulrich; Domschke, Katharina

    2016-07-01

    Anxiety disorders constitute the largest group of mental disorders with a high individual and societal burden. Neurobiological markers of treatment response bear potential to improve response rates by informing stratified medicine approaches. A systematic review was performed on the current evidence of the predictive value of genetic, neuroimaging and other physiological markers for treatment response (pharmacological and/or psychotherapeutic treatment) in anxiety disorders. Studies published until March 2015 were selected through search in PubMed, Web of Science, PsycINFO, Embase, and CENTRAL. Sixty studies were included, among them 27 on genetic, 17 on neuroimaging and 16 on other markers. Preliminary evidence was found for the functional 5-HTTLPR/rs25531 genotypes, anterior cingulate cortex function and cardiovascular flexibility to modulate treatment outcome. Studies varied considerably in methodological quality. Application of more stringent study methodology, predictions on the individual patient level and cross-validation in independent samples are recommended to set the next stage of biomarker research and to avoid flawed conclusions in the emerging field of "Mental Health Predictomics". Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Corns in dogs; signalment, possible aetiology and response to surgical treatment.

    PubMed

    Guilliard, M J; Segboer, I; Shearer, D H

    2010-03-01

    To describe the signalment and response to surgical treatment, and to propose aetiopathogenetic mechanisms for the development of paw pad corns in dogs. A combined retrospective and prospective study was conducted on 30 dogs that presented with paw pad corns. The age, breed and gender of the dogs, together with anatomical positions of the corns were recorded. Surgical treatments involved either excision (n=27) or distal digital ostectomy (n=3). The minimum follow-up period was one year. The age at presentation was from two to 15 years. All the breeds in this study were either greyhounds or sighthounds. Males were over-represented. Ninety percent of the corns were found in the digital pads of digits three and four, and 90% were found in the thoracic limbs. The evidence suggests a mechanical aetiology or foreign body penetration. Long-term response to surgical excision resulted in a recurrence rate of more than 50% (n=27). Distal digital ostectomy gave good results in selective cases (n=3). Corns can cause severe chronic lameness in greyhounds and related breeds. Long-term response to surgical treatments is disappointing but it is recommended as an initial treatment as it can be curative.

  11. The Role of Magnetic Resonance Imaging Biomarkers in Clinical Trials of Treatment Response in Cancer

    PubMed Central

    Yankeelov, Thomas E.; Arlinghaus, Lori A.; Li, Xia; Gore, John C.

    2010-01-01

    Current standard-of-care radiological methods for assessing the response of solid tumors to treatment are based on measuring changes in lesion size in a single dimension using high-resolution x-ray computed tomography or magnetic resonance imaging (MRI). Even if size measurements are adapted to record true volume changes more accurately, the effects of therapeutic drugs on tumor size may not occur for several cycles of treatment. Furthermore, current and future generations of anti-cancer drugs will be designed to affect highly specific cancer characteristics, and their effects may not be immediately cytotoxic. More sensitive and specific measures are required that can report on tumor status and treatment response early in the course of therapy. Several MRI techniques have matured to the point where they can offer quantitative information on tissue status and greater insight into specific biophysical and physiological characteristics of tumors. Here we review and provide illustrative examples of two MRI methods that have already been incorporated into clinical trials of treatment response in solid tumors: diffusion imaging and dynamic contrast enhanced MRI. We also discuss the limitations and future research directions required for these techniques to gain greater acceptance and to have their maximum impact. PMID:21362513

  12. Akt inhibition improves irinotecan treatment and prevents cell emergence by switching the senescence response to apoptosis

    PubMed Central

    Vétillard, Alexandra; Jonchère, Barbara; Moreau, Marie; Toutain, Bertrand; Henry, Cécile; Fontanel, Simon; Bernard, Anne-Charlotte; Campone, Mario; Guette, Catherine; Coqueret, Olivier

    2015-01-01

    Activated in response to chemotherapy, senescence is a tumor suppressive mechanism that induces a permanent loss of proliferation. However, in response to treatment, it is not really known how cells can escape senescence and how irreversible or incomplete this pathway is. We have recently described that cells that escape senescence are more transformed than non-treated parental cells, they resist anoikis and rely on Mcl-1. In this study, we further characterize this emergence in response to irinotecan, a first line treatment used in colorectal cancer. Our results indicate that Akt was activated as a feedback pathway during the early step of senescence. The inhibition of the kinase prevented cell emergence and improved treatment efficacy, both in vitro and in vivo. This improvement was correlated with senescence inhibition, p21waf1 downregulation and a concomitant activation of apoptosis due to Noxa upregulation and Mcl-1 inactivation. The inactivation of Noxa prevented apoptosis and increased the number of emergent cells. Using either RNA interference or p21waf1-deficient cells, we further confirmed that an intact p53-p21-senescence pathway favored cell emergence and that its downregulation improved treatment efficacy through apoptosis induction. Therefore, although senescence is an efficient suppressive mechanism, it also generates more aggressive cells as a consequence of apoptosis inhibition. We therefore propose that senescence-inducing therapies should be used sequentially with drugs favoring cell death such as Akt inhibitors. This should reduce cell emergence and tumor relapse through a combined induction of senescence and apoptosis. PMID:26485768

  13. Plasma homovanillic acid levels in first-episode schizophrenia. Psychopathology and treatment response.

    PubMed

    Koreen, A R; Lieberman, J; Alvir, J; Mayerhoff, D; Loebel, A; Chakos, M; Amin, F; Cooper, T

    1994-02-01

    To examine plasma homovanillic acid (pHVA) levels in first-episode schizophrenia, to compare pHVA levels in patients and controls, and to assess the association of pHVA levels with psychopathology and treatment response. Forty-one patients entered the study, and pHVA levels were measured at baseline and on a weekly basis for up to 6 weeks of open standardized neuroleptic treatment. Psychopathology was evaluated with the Schedule for Affective Disorders and Schizophrenia, the Scale for Assessment of Negative Symptoms, and the Clinical Global Impressions scale. Ten healthy controls were used for comparison of baseline pHVA levels. No differences were observed between patients and controls. Baseline pHVA level was not associated with psychopathology but was associated with time to reach remission. Baseline pHVA levels and week-1 pHVA levels were higher in responders than nonresponders. Regardless of responsiveness, female participants had higher pHVA levels than male participants throughout the study. The pattern of pHVA levels with treatment was similar in all patients with a short-term rise initially and then a decrease toward baseline values. These findings suggest that pHVA levels have prognostic significance for response and time to reach remission. Qualitative and quantitative differences between first-episode patients' pHVA levels and studies using a long-term, neuroleptic-exposed population suggest that changes occur with neuroleptic treatment or the progression of the illness.

  14. Brain responses to biological motion predict treatment outcome in young children with autism

    PubMed Central

    Yang, D; Pelphrey, K A; Sukhodolsky, D G; Crowley, M J; Dayan, E; Dvornek, N C; Venkataraman, A; Duncan, J; Staib, L; Ventola, P

    2016-01-01

    Autism spectrum disorders (ASDs) are common yet complex neurodevelopmental disorders, characterized by social, communication and behavioral deficits. Behavioral interventions have shown favorable results—however, the promise of precision medicine in ASD is hampered by a lack of sensitive, objective neurobiological markers (neurobiomarkers) to identify subgroups of young children likely to respond to specific treatments. Such neurobiomarkers are essential because early childhood provides a sensitive window of opportunity for intervention, while unsuccessful intervention is costly to children, families and society. In young children with ASD, we show that functional magnetic resonance imaging-based stratification neurobiomarkers accurately predict responses to an evidence-based behavioral treatment—pivotal response treatment. Neural predictors were identified in the pretreatment levels of activity in response to biological vs scrambled motion in the neural circuits that support social information processing (superior temporal sulcus, fusiform gyrus, amygdala, inferior parietal cortex and superior parietal lobule) and social motivation/reward (orbitofrontal cortex, insula, putamen, pallidum and ventral striatum). The predictive value of our findings for individual children with ASD was supported by a multivariate pattern analysis with cross validation. Predicting who will respond to a particular treatment for ASD, we believe the current findings mark the very first evidence of prediction/stratification biomarkers in young children with ASD. The implications of the findings are far reaching and should greatly accelerate progress toward more precise and effective treatments for core deficits in ASD. PMID:27845779

  15. Young Stand Thinning and Diversity Study: Response of Songbird Community One Decade Post-Treatment

    USGS Publications Warehouse

    Hagar, Joan; Friesen, Cheryl

    2009-01-01

    The response of songbird assemblages to commercial thinning is likely to change as vegetation develops over time after thinning. The influence of thinning intensity and pattern on the timing of transitions in bird community composition following thinning is of interest to managers when a goal is to maintain diversity and accelerate the development of late-seral forest structure. We investigated changes in the composition of songbird assemblages and density of individual species from 2 years before to 12 years after experimental thinning of 40-year-old stands dominated by Douglas-fir (Pseudotsuga menziesii) in the Oregon Cascades. Species richness, and density for five species and the neotropical migrant group were greater in thinned than in unthinned control stands over all post-treatment years of the study. Similarly, three species maintained a negative response to thinning over the post-treatment period. The initial positive influence of thinning was no longer in evidence a decade after harvest for five species. Of seven species with an initial negative response to thinning, three indicated recovery towards pre-treatment densities by the end of the most recent post-treatment survey. Our study is one of the first to document long-term effects of commercial thinning on forest songbird assemblages in the Pacific Northwest.

  16. Novel enzymatic assay predicts minoxidil response in the treatment of androgenetic alopecia.

    PubMed

    Goren, Andy; Castano, Juan Antonio; McCoy, John; Bermudez, Fernando; Lotti, Torello

    2014-01-01

    Topical minoxidil is the most common drug used for the treatment of androgenetic alopecia (AGA) in men and women. Although topical minoxidil exhibits a good safety profile, the efficacy in the overall population remains relatively low at 30-40%. To observe significant improvement in hair growth, minoxidil is typically used daily for a period of at least 3-4 months. Due to the significant time commitment and low response rate, a biomarker for predicting patient response prior to therapy would be advantageous. Minoxidil is converted in the scalp to its active form, minoxidil sulfate, by the sulfotransferase enzyme SULT1A1. We hypothesized that SULT1A1 enzyme activity in the hair follicle correlates with minoxidil response for the treatment of AGA. Our preliminary retrospective study of a SULT1A1 activity assay demonstrates 95% sensitivity and 73% specificity in predicting minoxidil treatment response for AGA. A larger prospective study is now under way to further validate this novel assay. © 2013 Wiley Periodicals, Inc.

  17. Subtyping Schizophrenia by Treatment Response: Antipsychotic Development and the Central Role of Positive Symptoms.

    PubMed

    Lee, Jimmy; Takeuchi, Hiroyoshi; Fervaha, Gagan; Sin, Gwen Li; Foussias, George; Agid, Ofer; Farooq, Saeed; Remington, Gary

    2015-11-01

    We have recently proposed a model for subtyping schizophrenia based on antipsychotic (AP) treatment response. Evidence suggests that APs, both old and new, are comparable in terms of efficacy; however, one AP, clozapine, is uniquely effective in one subgroup of patients (that is, those with treatment-resistant schizophrenia [TRS]). This permits us to subdivide schizophrenia into 3 specific groups: AP responsive, clozapine responsive, and clozapine resistant. Here, we integrate this model with current criteria related to TRS and ultraresistant schizophrenia, the latter referred to in our model as clozapine resistant. We suggest several modifications to existing criteria, in line with current evidence and practice patterns, particularly emphasizing the need to focus on positive symptoms. While APs can favourably impact numerous dimensions related to schizophrenia, it is their effect on positive symptoms that distinguishes them from other psychotropics. Further, it is positive symptoms that are central to AP and clozapine resistance, and it is these people that place the greatest demands on acute and long-term inpatient resources. In moving AP development forward, we advocate specifically focusing on positive symptoms and capitalizing on the evidence we have of 3 subtypes of psychosis (that is, positive symptoms) based on treatment response, implicating 3 distinguishable forms of underlying pathophysiology. Conversely, pooling these groups risks obfuscating potentially identifiable differences. Such a position does not challenge the importance of dopamine D2 receptor blockade, but rather highlights the need to better isolate those other subgroups that require something more or entirely different.

  18. Effects of a chronic stress treatment on vaccinal response in lambs.

    PubMed

    Destrez, A; Boissy, A; Guilloteau, L; Andanson, S; Souriau, A; Laroucau, K; Chaillou, E; Deiss, V

    2017-05-01

    Farming systems can expose animals to chronic mild stress which is known to induce negative affective state. Affective state in animals, as in humans, can be assessed through behavioral cues. This study aimed to describe the effect of a chronic mild stress, known to induce a negative affective state, on sheep health through their response to vaccination. The study used 15 lambs subjected to a model of chronic mild stress for 15 weeks and 15 lambs reared under conventional farming as a control group. After 7 weeks of stressful treatment, the lambs were individually exposed to a judgment bias test to assess a putative stress-induced 'pessimism.' After 15 weeks of stressful treatment, antibody immune response was measured after an injection of a live vaccine challenge (Chlamydia abortus attenuated vaccine strain 1B). Stressed lambs displayed a pessimistic-like perception in the judgment bias test, revealing a negative affective state. Stressed and control animals showed different immunological reactions to vaccine challenge: stressed sheep had lower hemoglobin concentrations and higher platelet, granulocyte and acute-phase protein concentrations. Antibody response induced by the vaccine strain was not different between stressed and control sheep. Our results suggest that negative affective state induced by chronic stress treatment may induce a stronger inflammatory response to vaccine challenge in sheep. Improvement of animal health may be achieved through consideration of stressors that may affect the emotional and immunological state of sheep.

  19. Subtyping Schizophrenia by Treatment Response: Antipsychotic Development and the Central Role of Positive Symptoms

    PubMed Central

    Lee, Jimmy; Takeuchi, Hiroyoshi; Fervaha, Gagan; Sin, Gwen Li; Foussias, George; Agid, Ofer; Farooq, Saeed; Remington, Gary

    2015-01-01

    We have recently proposed a model for subtyping schizophrenia based on antipsychotic (AP) treatment response. Evidence suggests that APs, both old and new, are comparable in terms of efficacy; however, one AP, clozapine, is uniquely effective in one subgroup of patients (that is, those with treatment-resistant schizophrenia [TRS]). This permits us to subdivide schizophrenia into 3 specific groups: AP responsive, clozapine responsive, and clozapine resistant. Here, we integrate this model with current criteria related to TRS and ultraresistant schizophrenia, the latter referred to in our model as clozapine resistant. We suggest several modifications to existing criteria, in line with current evidence and practice patterns, particularly emphasizing the need to focus on positive symptoms. While APs can favourably impact numerous dimensions related to schizophrenia, it is their effect on positive symptoms that distinguishes them from other psychotropics. Further, it is positive symptoms that are central to AP and clozapine resistance, and it is these people that place the greatest demands on acute and long-term inpatient resources. In moving AP development forward, we advocate specifically focusing on positive symptoms and capitalizing on the evidence we have of 3 subtypes of psychosis (that is, positive symptoms) based on treatment response, implicating 3 distinguishable forms of underlying pathophysiology. Conversely, pooling these groups risks obfuscating potentially identifiable differences. Such a position does not challenge the importance of dopamine D2 receptor blockade, but rather highlights the need to better isolate those other subgroups that require something more or entirely different. PMID:26720509

  20. [Occlusion treatment for amblyopia. Age dependence and dose-response relationship].

    PubMed

    Fronius, M

    2016-04-01

    Based on clinical experience and studies on animal models the age of 6-7 years was regarded as the limit for treatment of amblyopia, although functional improvement was also occasionally reported in older patients. New technical developments as well as insights from clinical studies and the neurosciences have attracted considerable attention to this topic. Various aspects of the age dependence of amblyopia treatment are discussed in this article, e. g. prescription, electronic monitoring of occlusion dosage, calculation of indicators for age-dependent plasticity of the visual system, and novel, alternative treatment approaches. Besides a discussion of the recent literature, results of studies by our "Child Vision Research Unit" in Frankfurt are presented: results of a questionnaire about prescription habits concerning age limits of patching, electronic recording of occlusion in patients beyond the conventional treatment age, calculation of dose-response function and efficiency of patching and their age dependence. The results of the questionnaire illustrate the uncertainty about age limits of prescription with significant deviations from the guideline of the German Ophthalmological Society (DOG). Electronic recording of occlusion allowed the quantification of declining dose-response function and treatment efficiency between 5 and 16 years of age. Reports about successful treatment with conventional and novel methods in adults are at variance with the notion of a rigid adult visual system lacking plasticity. Electronic recording of patching allowed new insights into the age-dependent susceptibility of the visual system and contributes to a more evidence-based treatment of amblyopia. Alternative approaches for adults challenge established notions about age limits of amblyopia therapy. Further studies comparing different treatment options are urgently needed.

  1. Pre-treatment prediction of response to peginterferon plus ribavirin in chronic hepatitis C genotype 3

    PubMed Central

    Marciano, Sebastián; Borzi, Silvia M; Dirchwolf, Melisa; Ridruejo, Ezequiel; Mendizabal, Manuel; Bessone, Fernando; Sirotinsky, María E; Giunta, Diego H; Trinks, Julieta; Olivera, Pablo A; Galdame, Omar A; Silva, Marcelo O; Fainboim, Hugo A; Gadano, Adrián C

    2015-01-01

    AIM: To evaluate pre-treatment factors associated with sustained virological response (SVR) in patients with hepatitis C virus (HCV) genotype 3 treated with peginterferon and ribavirin (RBV). METHODS: We retrospectively analyzed treatment naive, mono-infected HCV genotype 3 patients treated with peginterferon and RBV. Exclusion criteria included presence of other liver disease, alcohol consumption and African American or Asian ethnicity. The variables collected and compared between patients who achieved an SVR and patients who did not were as follows: gender, age, fibrosis stage, diabetes, body mass index, steatosis, INFL3 polymorphism, pre-treatment HCV-RNA, type of peginterferon, RBV dose and adherence. RESULTS: A total of 107 patients treated between June, 2004 and March, 2013 were included. Mean treatment duration was 25.1 (± 1.8) wk. Overall, 58% (62/107) of the patients achieved an SVR and 42% (45/107) did not. In the multivariate logistic regression analysis, pre-treatment HCV-RNA ≥ 600000 UI/mL (OR = 0.375, 95%CI: 0.153-0.919, P = 0.032) and advanced fibrosis (OR = 0.278, 95%CI: 0.113-0.684, P = 0.005) were significantly associated with low SVR rates. In patients with pre-treatment HCV-RNA ≥ 600000 UI/mL and advanced fibrosis, the probability of achieving an SVR was 29% (95%CI: 13.1-45.2). In patients with pre-treatment HCV-RNA < 600000 UI/mL and mild to moderate fibrosis, the probability of achieving an SVR was 81% (95%CI: 68.8-93.4). CONCLUSION: In patients with HCV genotype 3 infections the presence of advance fibrosis and high pre-treatment viral load might be associated with poor response to peginterferon plus RBV. These patients could benefit the most from new direct antiviral agents-based regimes. PMID:25866607

  2. Markers of Differential Response to Inhaled Corticosteroid Treatment among Children with Mild Persistent Asthma

    PubMed Central

    Gerald, Joe K.; Gerald, Lynn B.; Vasquez, Monica M.; Morgan, Wayne J; Boehmer, Susan J; Lemanske, Robert F; Mauger, David T.; Strunk, Robert C.; Szefler, Stanley J; Zeiger, Robert S; Bacharier, Leonard B.; Bade, Elizabeth; Covar, Ronina A.; Guilbert, Theresa W; Heidarian-Raissy, Hengameh; Kelly, H William; Malka-Rais, Jonathan; Sorkness, Christine A.; Taussig, Lynn; Chinchilli, Vernon M.; Martinez, Fernando D.

    2015-01-01

    Background Inhaled corticosteroids (ICSs) are recommended as first-line therapy for children with mild persistent asthma; however, specific patient characteristics may modify the treatment response. Objective Identify demographic, clinical, and atopic characteristics that may modify the ICS treatment response among children enrolled in the Treating Children to Prevent Exacerbations of Asthma (TREXA) trial. Methods Children age 6-18 years with mild persistent asthma were randomized to 44 weeks of combined, daily, rescue, or placebo treatment. Daily treatment consisted of 40 mcg of beclomethasone twice daily. Rescue treatment consisted of 40 mcg beclomethasone accompanying each symptom-driven albuterol actuation. Combined treatment consisted of both. Outcomes included time to first exacerbation and proportion of asthma control days. Fourteen baseline characteristics were selected for interaction testing based on their clinical relevance. Results Two-hundred-eighty-eight children were randomized. Seventy-five percent were white and 55% were male. As measured by time to first exacerbation, 4 characteristics identified children who received greater benefit from treatment: non-Hispanic ethnicity, positive aeroallergen skin test, serum immunoglobulin E level ≥350 K/μL, and history of oral corticosteroid use in the year prior to enrollment. As measured by asthma control days, 4 characteristics identified children who received greater benefit from treatment: male sex, positive aeroallergen skin test, serum immunoglobulin E level ≥350 K/μL, and incomplete run-in asthma control. Conclusions Children with mild persistent asthma who have markers of atopic asthma or who have greater asthma burden may obtain greater benefit from beclomethasone therapy. Additional study is needed to confirm whether these markers can guide individualized therapy. PMID:25783161

  3. Anxiety Diagnoses in Smokers Seeking Cessation Treatment: Relations with Tobacco Dependence, Withdrawal, Outcome, and Response to Treatment

    PubMed Central

    Piper, Megan E.; Cook, Jessica W.; Schlam, Tanya R.; Jorenby, Douglas E.; Baker, Timothy B.

    2010-01-01

    Aims To understand the relations amongst anxiety disorders and tobacco dependence, withdrawal symptoms, response to smoking cessation pharmacotherapy, and ability to quit smoking. Design Randomized placebo-controlled clinical trial. Participants received six 10-minute individual counseling sessions and either: placebo, bupropion SR, nicotine patch, nicotine lozenge, bupropion SR+nicotine lozenge, or nicotine patch+nicotine lozenge. Setting Two urban research sites. Participants Data were collected from 1504 daily smokers (>9 cigarettes per day) who were motivated to quit smoking and did not report current diagnoses of schizophrenia or psychosis or bupropion use. Measurements Participants completed baseline assessments, the Composite International Diagnostic Interview and ecological momentary assessments for two weeks. Findings A structured clinical interview identified participants who ever met criteria for a panic attack (n=455), social anxiety (n=199), or generalized anxiety disorder (n=99), and those who qualified for no anxiety diagnosis (n=891). Smokers with anxiety disorders reported higher levels of nicotine dependence and pre-quit withdrawal symptoms. Those ever meeting criteria for panic attacks or social anxiety disorder showed greater quit-day negative affect. Smokers ever meeting criteria for anxiety disorders were less likely to be abstinent at 8-weeks and 6-months postquit and showed no benefit from single-agent or combination-agent pharmacotherapies. Conclusions Anxiety diagnoses were common amongst treatment-seeking smokers and were related to increased motivation to smoke, elevated withdrawal, lack of response to pharmacotherapy, and impaired ability to quit smoking. These findings could guide treatment assignment algorithms and treatment development for smokers with anxiety diagnoses. PMID:20973856

  4. Influence of race/ethnicity on response to lupus nephritis treatment: the ALMS study

    PubMed Central

    Isenberg, David; Appel, Gerald B.; Contreras, Gabriel; Dooley, Mary A.; Ginzler, Ellen M.; Jayne, David; Sánchez-Guerrero, Jorge; Wofsy, David; Yu, Xueqing

    2010-01-01

    Objective. To compare the efficacy and safety of mycophenolate mofetil (MMF) and intravenous cyclophosphamide (IVC) as induction treatment for lupus nephritis (LN), by race, ethnicity and geographical region. Methods. A total of 370 patients with active Class III–V LN received MMF (target dose 3.0 g/day) or IVC (0.5–1.0 g/m2/month), plus tapered prednisone, for 24 weeks. Renal function, global disease activity, immunological complement (C3 and C4) and anti-dsDNA levels are the outcomes that were assessed in this study. Results. MMF was not superior to IVC as induction treatment (primary objective). There were important pre-specified interactions between treatment and race (P = 0.047) and treatment and region (P = 0.069) (primary endpoint). MMF and IVC response rates were similar for Asians (53.2 vs 63.9%; P = 0.24) and Whites (56.0 vs 54.2%; P = 0.83), but differed in the combined Other and Black group (60.4 vs 38.5%; P = 0.03). Fewer patients in the Black (40 vs 53.9%; P = 0.39) and Hispanic (38.8 vs 60.9%; P = 0.011) groups responded to IVC. Latin American patients had lower response to IVC (32 vs 60.7%; P = 0.003). Baseline disease characteristics were not predictive of response. The incidence of adverse events (AEs) was similar across groups. Serious AEs were slightly more prevalent among Asians. Conclusions. MMF and IVC have similar efficacy overall to short-term induction therapy for LN. However, race, ethnicity and geographical region may affect treatment response; more Black and Hispanic patients responded to MMF than IVC. As these factors are inter-related, it is difficult to draw firm conclusions about their importance. Trial registration. National Institutes of Health, www.clinicaltrials.gov, registration number NCT00377637. PMID:19933596

  5. Glucocorticoid Genes and the Developmental Origins of Asthma Susceptibility and Treatment Response

    PubMed Central

    Kho, Alvin T.; Chhabra, Divya; Qiu, Weiliang; Gaedigk, Roger; Vyhlidal, Carrie A.; Leeder, J. Steven; Barraza-Villarreal, Albino; London, Stephanie J.; Gilliland, Frank; Raby, Benjamin A.; Weiss, Scott T.; Tantisira, Kelan G.

    2015-01-01

    Antenatal corticosteroids enhance lung maturation. However, the importance of glucocorticoid genes on early lung development, asthma susceptibility, and treatment response remains unknown. We investigated whether glucocorticoid genes are important during lung development and their role in asthma susceptibility and treatment response. We identified genes that were differentially expressed by corticosteroids in two of three genomic datasets: lymphoblastoid cell lines of participants in the Childhood Asthma Management Program, a glucocorticoid chromatin immunoprecipitation/RNA sequencing experiment, or a murine model; these genes made up the glucocorticoid gene set (GCGS). Using gene expression profiles from 38 human fetal lungs and C57BL/6J murine fetal lungs, we identified developmental genes that were in the top 5% of genes contributing to the top three principal components (PCs) most highly associated with post-conceptional age. Glucocorticoid genes that were enriched in this set of developmental genes were then included in the developmental glucocorticoid gene set (DGGS). We then investigated whether glucocorticoid genes are important during lung development, and their role in asthma susceptibility and treatment response. A total of 232 genes were included in the GCGS. Analysis of gene expression demonstrated that glucocorticoid genes were enriched in lung development (P = 7.02 × 10−26). The developmental GCGS was enriched for genes that were differentially expressed between subjects with asthma and control subjects (P = 4.26 × 10−3) and were enriched after treatment of subjects with asthma with inhaled corticosteroids (P < 2.72 × 10−4). Our results show that glucocorticoid genes are overrepresented among genes implicated in fetal lung development. These genes influence asthma susceptibility and treatment response, suggesting their involvement in the early ontogeny of asthma. PMID:25192440

  6. The Responsiveness of Patients' Quality of Life to Dental Caries Treatment-A Prospective Study.

    PubMed

    Yeh, Ding-Yu; Kuo, Hsiao-Ching; Yang, Yi-Hsin; Ho, Pei-Shan

    2016-01-01

    The objective of this study was to determine the responsiveness of oral health-related quality of life (OHRQoL) (oral health impact profile [OHIP] and oral impact on daily performance [OIDP]) and health-related quality of life (HRQoL) (World Health Organization quality of life scale, brief [WHOQOL-BREF]) in dental caries restoration treatment. The study also aimed to assess the influence of treatment on the responsiveness of patients' quality of life (QoL). A total of 126 patients (aged 16-40 years) received dental caries restoration treatment with a 2-week follow-up and pre- and posttreatment interviews by questionnaire. Patients were assessed for their perceptions of OHRQoL and HRQoL by using the OHIP, OIDP, and WHOQOL-BREF measures. The responsiveness of all outcome measurements was assessed by effect size (ES). Stepwise multiple regression analysis was used to examine the association with the responsiveness of all outcome measurements. Significant differences were found between OIDP (ES = 0.39), OHIP (ES = 0.54), and WHOQOL-BREF (ES = 0.13) with regard to pretreatment and posttreatment (p-values: <0.0001, <0.0001, and 0.0120, respectively). Sex and dental caries status at baseline were significantly associated with responsiveness by all measurements. This study suggests that dental caries treatment moderately improves OHRQoL, but is less related to HRQoL. Furthermore, the number of dental caries and restoration are important factors affecting the improvement of patients' perceived OHRQoL.

  7. Metabolic Imaging to Assess Treatment Response to Cytotoxic and Cytostatic Agents

    PubMed Central

    Serkova, Natalie J.; Eckhardt, S. Gail

    2016-01-01

    For several decades, cytotoxic chemotherapeutic agents were considered the basis of anticancer treatment for patients with metastatic tumors. A decrease in tumor burden, assessed by volumetric computed tomography and magnetic resonance imaging, according to the response evaluation criteria in solid tumors (RECIST), was considered as a radiological response to cytotoxic chemotherapies. In addition to RECIST-based dimensional measurements, a metabolic response to cytotoxic drugs can be assessed by positron emission tomography (PET) using 18F-fluoro-thymidine (FLT) as a radioactive tracer for drug-disrupted DNA synthesis. The decreased 18FLT-PET uptake is often seen concurrently with increased apparent diffusion coefficients by diffusion-weighted imaging due to chemotherapy-induced changes in tumor cellularity. Recently, the discovery of molecular origins of tumorogenesis led to the introduction of novel signal transduction inhibitors (STIs). STIs are targeted cytostatic agents; their effect is based on a specific biological inhibition with no immediate cell death. As such, tumor size is not anymore a sensitive end point for a treatment response to STIs; novel physiological imaging end points are desirable. For receptor tyrosine kinase inhibitors as well as modulators of the downstream signaling pathways, an almost immediate inhibition in glycolytic activity (the Warburg effect) and phospholipid turnover (the Kennedy pathway) has been seen by metabolic imaging in the first 24 h of treatment. The quantitative imaging end points by magnetic resonance spectroscopy and metabolic PET (including 18F-fluoro-deoxy-glucose, FDG, and total choline) provide an early treatment response to targeted STIs, before a reduction in tumor burden can be seen. PMID:27471678

  8. Vitamin D and the racial difference in the genotype 1 chronic hepatitis C treatment response.

    PubMed

    Weintraub, Steven J; Fleckenstein, Jacquelyn F; Marion, Tony N; Madey, Margaret A; Mahmoudi, Tahar M; Schechtman, Kenneth B

    2012-11-01

    African Americans with genotype 1 chronic hepatitis C attain a sustained virologic response (SVR) at only approximately one-half the rate of whites after peginterferon and ribavirin treatment. The serum concentration of 25-hydroxyvitamin D [25(OH)D] has recently been established as a predictor of treatment response. Therefore, the low serum concentrations of 25(OH)D found among African Americans may contribute to the low response rate; however, to our knowledge, none of the studies of vitamin D in chronic hepatitis C treatment have included a significant number of black patients. The objective was to compare the relation between the 25(OH)D concentration and genotype 1 chronic hepatitis C treatment response in African Americans with that in whites. This cross-sectional analysis included 106 African American and 65 white patients with genotype 1 chronic hepatitis C. Consistent with previous studies, we found that the SVR rate in the white patients increased significantly with an increasing serum concentration of 25(OH)D [SVR rates were 20%, 46%, and 70% for 25(OH)D serum concentrations <20, 20-35, and >35 ng/mL, respectively; P-trend = 0.008]; however, there was no relation between the SVR rate and 25(OH)D serum concentration in the African American patients [SVR rates were 32%, 28%, and 33% for 25(OH)D serum concentrations <20, 20-35, and >35 ng/mL, respectively; P-trend = 0.832]. We also found an analogous racial difference in the relation between the extent of liver fibrosis and the 25(OH)D concentration. Racial differences in vitamin D physiology or race-specific factors that modify the effects of vitamin D may affect the immune response to genotype 1 hepatitis C virus.

  9. Response to Laser Treatment of Café au Lait Macules Based on Morphologic Features.

    PubMed

    Belkin, Daniel A; Neckman, Julia P; Jeon, Hana; Friedman, Paul; Geronemus, Roy G

    2017-08-30

    Response to laser treatment for café au lait macules (CALMs) is inconsistent and difficult to predict. To test the hypothesis that irregularly bordered CALMs of the "coast of Maine" subtype respond better to treatment than those of the smooth-bordered "coast of California" subtype. This retrospective case series included patients from 2 multiple-clinician US practices treated from 2005 through 2016. All patients had a clinical diagnosis of CALM and were treated with a Q-switched or picosecond laser. A total of 51 consecutive patients were eligible, 6 of whom were excluded owing to ambiguous lesion subtype. Observers were blinded to final patient groupings. Treatment with 755-nm alexandrite picosecond laser, Q-switched ruby laser, Q-switched alexandrite laser, or Q-switched 1064-nm Nd:YAG laser. Main outcome was grade in a visual analog scale (VAS) consisting of 4 levels of treatment response: poor (grade 1, 0%-25% improvement), fair (grade 2, 26%-50% improvement), good (grade 3, 51%-75% improvement), and excellent (grade 4, 76%-100% improvement). Forty-five patients were included in the series, 19 with smooth-bordered lesions and 26 with irregularly bordered lesions. Thirty-four (76%) of the participants were female; 33 (73%) were white; and the mean age at the time of laser treatment was 14.5 years (range, 0-44 years). Smooth-bordered lesions received a mean VAS score of 1.76, corresponding to a fair response on average (26%-50% pigmentary clearance). Irregularly bordered lesions received a mean VAS score of 3.67, corresponding to an excellent response on average (76%-100% clearance) (P < .001). CALMs with jagged or ill-defined borders of the coast of Maine subtype tend to respond well to laser treatment, whereas those with smooth and well-defined borders of the coast of California subtype tend to have poor response. Clinicians using Q-switched or picosecond lasers to treat CALMs can use morphologic characteristics to help predict response and more

  10. Impaired response or insufficient dosage? Examining the potential causes of "inadequate response" to allopurinol in the treatment of gout.

    PubMed

    Stamp, Lisa K; Merriman, Tony R; Barclay, Murray L; Singh, Jasvinder A; Roberts, Rebecca L; Wright, Daniel F B; Dalbeth, Nicola

    2014-10-01

    Gout is one of the most common forms of arthritis. It is well established that urate-lowering therapy that aims for a serum urate less than at least 0.36 mmol/l (6 mg/dl) is required for the successful management of gout. Allopurinol, a xanthine oxidase (XO) inhibitor, is the most commonly used urate-lowering therapy. However, many patients fail to achieve the target serum urate on allopurinol; these patients can be considered to have "inadequate response" to allopurinol. Herein, we examine the potential mechanisms and implications of inadequate response to allopurinol. The literature was reviewed for potential causes for failure to reach target serum urate in patients receiving allopurinol. The two most common causes of inadequate response to allopurinol are poor adherence and under-dosing of allopurinol. Adherent patients who fail to achieve target serum urate on standard doses of allopurinol form a group that could be considered to be "partially resistant" to allopurinol. There are four potential mechanisms for partial allopurinol resistance: decreased conversion of allopurinol to oxypurinol; increased renal excretion of oxypurinol; abnormality in XO structure and/or function such that oxypurinol is rendered less effective and/or drug interactions. It is important to determine the reasons for failure to achieve treatment targets with allopurinol, particularly as newer agents become available. The knowledge of the mechanisms for inadequate response may help guide the clinician towards making a therapeutic choice that is more likely to result in achieving the serum urate target. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. Serial diffusion MRI to monitor and model treatment response of the targeted nanotherapy CRLX101.

    PubMed

    Ng, Thomas S C; Wert, David; Sohi, Hargun; Procissi, Daniel; Colcher, David; Raubitschek, Andrew A; Jacobs, Russell E

    2013-05-01

    Targeted nanotherapies are being developed to improve tumor drug delivery and enhance therapeutic response. Techniques that can predict response will facilitate clinical translation and may help define optimal treatment strategies. We evaluated the efficacy of diffusion-weighted magnetic resonance imaging to monitor early response to CRLX101 (a cyclodextrin-based polymer particle containing the DNA topoisomerase I inhibitor camptothecin) nanotherapy (formerly IT-101), and explored its potential as a therapeutic response predictor using a mechanistic model of tumor cell proliferation. Diffusion MRI was serially conducted following CRLX101 administration in a mouse lymphoma model. Apparent diffusion coefficients (ADCs) extracted from the data were used as treatment response biomarkers. Animals treated with irinotecan (CPT-11) and saline were imaged for comparison. ADC data were also input into a mathematical model of tumor growth. Histological analysis using cleaved-caspase 3, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling, Ki-67, and hematoxylin and eosin (H&E) were conducted on tumor samples for correlation with imaging results. CRLX101-treated tumors at day 2, 4, and 7 posttreatment exhibited changes in mean ADC = 16 ± 9%, 24 ± 10%, 49 ± 17%, and size (TV) = -5 ± 3%, -30 ± 4%, and -45 ± 13%, respectively. Both parameters were statistically greater than controls [p(ADC) ≤ 0.02, and p(TV) ≤ 0.01 at day 4 and 7], and noticeably greater than CPT-11-treated tumors (ADC = 5 ± 5%, 14 ± 7%, and 18 ± 6%; TV = -15 ± 5%, -22 ± 13%, and -26 ± 8%). Model-derived parameters for cell proliferation obtained using ADC data distinguished CRLX101-treated tumors from controls (P = 0.02). Temporal changes in ADC specified early CRLX101 treatment response and could be used to model image-derived cell proliferation rates following treatment. Comparisons of targeted and nontargeted treatments highlight the utility of noninvasive imaging and modeling

  12. Pivotal response treatment for preschoolers with autism spectrum disorder: Defining a predictor profile.

    PubMed

    Fossum, Kristin-Lee; Williams, Loriann; Garon, Nancy; Bryson, Susan E; Smith, Isabel M

    2017-08-31

    Behavioral characteristics of children with autism spectrum disorder (ASD) who respond positively to Pivotal Response Treatment (PRT) have been described previously, based on single-subject design research. The present study examined several such characteristics, as well as positive affect, as predictors of expressive language (EL) gains in a representative sample of preschoolers with ASD (n = 57) enrolled in a PRT-based community early intervention program. Children's cognitive ability, positive affect, and levels of appropriate toy contact measured at the start of intervention each contributed significantly to the prediction of EL outcomes. Together these variables accounted for 40% of the total outcome variance. In addition, a profile of increased EL ability, positive affect and appropriate toy contact, and decreased social avoidance and stereotyped and repetitive vocalizations was associated with greater gains during intervention. Results are discussed in relation to their implications for understanding both the variable treatment response documented in children with ASD and how to tailor treatment to optimize individual benefit. Autism Res 2017. © 2017 International Society for Autism Research, Wiley Periodicals, Inc. The study examined behavior of 57 preschoolers who made the greatest and least gains from 1 year of a community Pivotal Response Treatment program. Using pre-treatment videos, we saw that children who made the most progress showed more language, positive affect, and appropriate interactions with toys, also less avoidance of people and fewer repetitive vocalizations. Behavior profiles can be used to match treatment to individual children's needs. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.

  13. Enhancement of gas sensor response of nanocrystalline zinc oxide for ammonia by plasma treatment

    NASA Astrophysics Data System (ADS)

    Hou, Yue; Jayatissa, Ahalapitiya H.

    2014-08-01

    The effect of oxygen plasma treatment on nanocrystalline ZnO thin film based gas sensor was investigated. ZnO thin films were synthesized on alkali-free glass substrates by a sol-gel process. ZnO thin films were treated with oxygen plasma to change the number of vacancies/defects in ZnO. The effect of oxygen plasma on the structural, electrical, optical and gas sensing properties was investigated as a function of plasma treatment time. The results suggest that the microstructure and the surface morphology can be tuned by oxygen plasma treatment. The optical transmission in the visible range varies after the oxygen plasma treatment. Moreover, it is found that the oxygen plasma has significant impact on the electrical properties of ZnO thin films indicating a variation of resistivity. The oxygen plasma treated ZnO thin film exhibits an enhanced sensing response towards NH3 in comparison with that of the as-deposited ZnO sensor. When compared with the as-deposited ZnO film, the sensing response was improved by 50% for the optimum oxygen plasma treatment time of 8 min. The selectivity of 8 min plasma treated ZnO sensor was also examined for an important industrial gas mixture of H2, CH4 and NH3.

  14. EEG biomarkers in major depressive disorder: discriminative power and prediction of treatment response.

    PubMed

    Olbrich, Sebastian; Arns, Martijn

    2013-10-01

    Major depressive disorder (MDD) has high population prevalence and is associated with substantial impact on quality of life, not least due to an unsatisfactory time span of sometimes several weeks from initiation of treatment to clinical response. Therefore extensive research focused on the identification of cost-effective and widely available electroencephalogram (EEG)-based biomarkers that not only allow distinguishing between patients and healthy controls but also have predictive value for treatment response for a variety of treatments. In this comprehensive overview on EEG research on MDD, biomarkers that are either assessed at baseline or during the early course of treatment and are helpful in discriminating patients from healthy controls and assist in predicting treatment outcome are reviewed, covering recent decades up to now. Reviewed markers include quantitative EEG (QEEG) measures, connectivity measures, EEG vigilance-based measures, sleep-EEG-related measures and event-related potentials (ERPs). Further, the value and limitations of these different markers are discussed. Finally, the need for integrated models of brain function and the necessity for standardized procedures in EEG biomarker research are highlighted to enhance future research in this field.

  15. Association between vitamin D receptor gene polymorphisms and response to treatment of pulmonary tuberculosis.

    PubMed

    Roth, Daniel E; Soto, Giselle; Arenas, Fanny; Bautista, Christian T; Ortiz, Jaime; Rodriguez, Richard; Cabrera, Lilia; Gilman, Robert H

    2004-09-01

    Polymorphisms in the gene that encodes the vitamin D receptor (VDR) may influence the host response to Mycobacterium tuberculosis infection. In a Peruvian community with a high incidence of tuberculosis (TB), VDR TaqI and FokI polymorphisms were compared among 103 patients with pulmonary TB and 206 matched healthy control subjects. Associations of VDR polymorphisms with treatment outcome were analyzed among 78 patients undergoing treatment of pulmonary TB. Sputum mycobacterial culture and auramine stain conversions were significantly faster among participants with the FokI FF genotype, compared with participants with the non-FF genotypes. Sputum culture conversion was faster among participants with the TaqI Tt genotype, compared with those with the TT genotype. Increased probability of culture conversion during TB treatment was independently associated with the TaqI Tt genotype (age- and sex-adjusted relative risk, 4.28; 95% confidence interval, 1.88-9.75; P = .001). VDR polymorphisms were not significantly associated with susceptibility to TB in the case-control study. VDR gene polymorphisms are associated with the time to sputum culture and auramine stain conversion during TB treatment. To our knowledge, the present study is the first report of a specific host gene influence on the outcome of TB treatment. These findings demonstrate the potential clinical relevance of immunomodulatory functions of vitamin D metabolites acting via the VDR in the host response against pulmonary TB.

  16. Immune Responses to Epidermal Growth Factor Receptor (EGFR) and Their Application for Cancer Treatment.

    PubMed

    Sasada, Tetsuro; Azuma, Koichi; Ohtake, Junya; Fujimoto, Yuki

    2016-01-01

    Epidermal growth factor receptor (EGFR) is a prototypic cell-surface receptor belonging to the ErbB/HER onocogene family. Overexpression or somatic mutations of EGFR have been reported to play an important role in tumorigenesis in various types of epithelial cancers. Therefore, targeting of EGFR with specific blocking antibodies or inhibitors have been developing for treatment for EGFR-associated tumors. Immune responses to HER2, another molecule of the ErbB/HER onocogene family, have been well studied, but only limited information on the immune responses to EGFR in cancer has been currently available. In this review, we have summarized the available data and discussed potential clinical importance of the anti-EGFR immune responses and EGFR-mediated immune regulation in cancer. Several lines of evidence suggest that cellular and humoral immune responses to EGFR might be useful as a marker and/or target for cancer therapy against EGFR-associated tumors. In addition, recent studies suggest the critical roles of EGFR-mediated signaling in regulation of expression of an immune checkpoint molecule, programmed death-ligand 1 (PD-L1) in tumor cells. Further studies are warranted to clarify the impact of the anti-EGFR immune responses and EGFR-mediated immunomodulation for clinical application for cancer treatment.

  17. Treatment with the selective serotonin reuptake inhibitor, fluoxetine, attenuates the fish hypoxia response

    PubMed Central

    Panlilio, Jennifer M.; Marin, Sara; Lobl, Marissa B.; McDonald, M. Danielle

    2016-01-01

    The selective serotonin reuptake inhibitor (SSRI) fluoxetine (FLX), the active ingredient of the antidepressant drug Prozac, inhibits reuptake of the neurotransmitter, serotonin (5-HT; 5-hydroxytryptamine), into cells by the 5-HT transporter (SERT). Given the role of 5-HT in oxygen detection and the cardiovascular and ventilatory responses of fish to hypoxia, we hypothesized that treatment of the Gulf toadfish, Opsanus beta, with FLX would interfere with their response to hypoxia. Toadfish treated intra-arterially with 3.4 μg.g−1 FLX under normoxic conditions displayed a transient tachycardia and a biphasic caudal arterial blood pressure (PCA) response that are in direct conflict with the typical hypoxia response. Fish injected intraperitoneally with FLX under normoxia had resting cardiovascular and ventilatory parameters similar to controls. Upon exposure to hypoxia, control toadfish exhibit a significant bradycardia, reduction in PCA and an increase in ventilatory amplitude (VAMP) without any changes in ventilatory frequency (fV). Fish treated IP with 10 μg.g−1 FLX showed an interference in the cardiovascular and ventilatory response to hypoxia. Interestingly, when treated with 25 μg.g−1 FLX, the bradycardia and VAMP response to hypoxia were similar to control fish while the PCA response to hypoxia was further inhibited. These results suggest that SERT inhibition by FLX may hinder survival in hypoxia. PMID:27499056

  18. Treatment with the selective serotonin reuptake inhibitor, fluoxetine, attenuates the fish hypoxia response.

    PubMed

    Panlilio, Jennifer M; Marin, Sara; Lobl, Marissa B; McDonald, M Danielle

    2016-08-08

    The selective serotonin reuptake inhibitor (SSRI) fluoxetine (FLX), the active ingredient of the antidepressant drug Prozac, inhibits reuptake of the neurotransmitter, serotonin (5-HT; 5-hydroxytryptamine), into cells by the 5-HT transporter (SERT). Given the role of 5-HT in oxygen detection and the cardiovascular and ventilatory responses of fish to hypoxia, we hypothesized that treatment of the Gulf toadfish, Opsanus beta, with FLX would interfere with their response to hypoxia. Toadfish treated intra-arterially with 3.4 μg.g(-1) FLX under normoxic conditions displayed a transient tachycardia and a biphasic caudal arterial blood pressure (PCA) response that are in direct conflict with the typical hypoxia response. Fish injected intraperitoneally with FLX under normoxia had resting cardiovascular and ventilatory parameters similar to controls. Upon exposure to hypoxia, control toadfish exhibit a significant bradycardia, reduction in PCA and an increase in ventilatory amplitude (VAMP) without any changes in ventilatory frequency (fV). Fish treated IP with 10 μg.g(-1) FLX showed an interference in the cardiovascular and ventilatory response to hypoxia. Interestingly, when treated with 25 μg.g(-1) FLX, the bradycardia and VAMP response to hypoxia were similar to control fish while the PCA response to hypoxia was further inhibited. These results suggest that SERT inhibition by FLX may hinder survival in hypoxia.

  19. Prediction of response to treatment in a randomized clinical trial of couple therapy: a 2-year follow-up.

    PubMed

    Baucom, Brian R; Atkins, David C; Simpson, Lorelei E; Christensen, Andrew

    2009-02-01

    Many studies have examined pretreatment predictors of immediate posttreatment outcome, but few studies have examined prediction of long-term treatment response to couple therapies. Four groups of predictors (demographic, intrapersonal, communication, and other interpersonal) and 2 moderators (pretreatment severity and type of therapy) were explored as predictors of clinically significant change measured 2 years after treatment termination. Results demonstrated that power processes and expressed emotional arousal were the strongest predictors of 2-year response to treatment. Moderation analyses showed that these variables predicted differential treatment response to traditional versus integrative behavioral couple therapy and that more variables predicted 2-year response for couples who were less distressed when beginning treatment. Findings are discussed with regard to existing work on prediction of treatment response, and directions for further study are offered.

  20. Ovarian response to gonadotropin treatment initiated relative to wave emergence in ultrasonographically monitored ewes.

    PubMed

    Rubianes, E; Ungerfeld, R; Viñoles, C; Rivero, A; Adams, G P

    1997-06-01

    Follicular recruitment and luteal response to superovulatory treatment initiated relative to the status of the first wave of the ovine estrous cycle (Wave 1) were studied. All ewes (n = 25) received an intravaginal progestagen sponge to synchronize estrous cycles, and ewes were monitored daily by transrectal ultrasonography. Multiple-dose FSH treatment (total dose = 100 mg NIH-FSH-P1) was initiated on the day of ovulation (Day 0 group) in 16 ewes. In the remaining 9 ewes, FSH treatment was started 3 d after emergence of the largest follicle of Wave 1 (Day 3 group). Ewes received PGF(2alpha) with the last 2 FSH treatments to induce luteolysis. Daily blood samples were taken to determine progesterone profiles and to evaluate the luteal response subsequent to superovulation. The ovulation rate was determined by ultrasonography and correlated with direct observation of the ovaries during laparotomy 5 to 6 d after superovulatory estrus when the uterus was flushed to collect embryos. Results confirmed that follicular recruitment was suppressed by the presence of a large, growing follicle. In the Day 0 and Day 3 groups, respectively, mean numbers (+/- SEM) of large follicles (>/= 4 mm) recruited were 6.4 +/- 0.6 and 2.7 +/- 0.7 (P < 0.01) at 48 h after the onset of treatment, and 6.7 +/- 0.5 and 5.1 +/- 0.6 (P = 0.08) at 72 h after the onset of treatment. Ovulation rates were 5.6 +/- 0.8 and 3.3 +/- 0.8 in the respective groups (P < 0.05). The number of transferable embryos was 1.8 +/- 0.5 and 0.3 +/- 0.2 in the respective groups (P < 0.05). Short luteal phases (treatment initiated at the time of emergence of Wave 1 induced a superovulatory response in ewes. Response was influenced by the status of the follicular wave. The presence of a large growing follicle

  1. The response of an assertive community treatment program following a natural disaster.

    PubMed

    Lachance, K R; Santos, A B; Burns, B J

    1994-10-01

    A newly forming model treatment program for seriously mentally ill adults was dramatically affected by a natural disaster in September 1989. Hurricane Hugo rendered the offices of the Assertive Community Treatment Program uninhabitable, its vehicles marginally driveable, and its resources virtually nonexistent. In the three months following the storm, however, not a single psychiatric rehospitalization took place. Although the authors cannot claim that the program model was solely responsible for this outcome, this paper illustrates the service system elements that contributed to the program's effectiveness in the wake of one of the nation's most severe natural disasters.

  2. An unusual neck tumor in a young pregnant woman: challenge diagnosis and response to treatment

    PubMed Central

    López, Juan C.; Arrazubi, Virginia; Cisneros, Silvia; Rodríguez, Angel; Zabala, Aitor; Martinez del Prado, Purificación

    2017-01-01

    Abstract We report the case of a 19-year-old woman 33 weeks pregnant who presented a painful mass of progressive growth in the neck, having also dysphonia and dyspnea. Physical examination revealed a primary laryngeal tumor. A neuroendocrine small-cell carcinoma was diagnosed after histopathology, immunohistochemistry and genetic studies. Chemo-radiotherapy with a cisplatin-etoposide schedule was administered. Despite obtaining a complete response, the patient relapsed and finally survived 35 months with successive cisplatin-based treatments. Small-cell neuroendocrine carcinoma of the larynx is an uncommon entity, differential diagnosis can be problematic and treatment is challenging. PMID:28852532

  3. Agouron and immune response to commercialize remune immune-based treatment.

    PubMed

    James, J S

    1998-06-19

    Agouron Pharmaceuticals agreed in June to collaborate with The Immune Response Corporation on the final development and marketing of an immune-based treatment for HIV. Remune, the vaccine developed by Dr. Jonas Salk, is currently in Phase III randomized trials with 2,500 patients, and the trials are expected to be completed in April 1999. Immune-based treatments have been difficult to test, as there is no surrogate marker, like viral load, to determine if the drug is working. Agouron agreed to participate in the joint venture after reviewing encouraging results from preliminary trials in which remune was taken in combination with highly active antiretroviral drugs.

  4. Behavioural treatment of tics: habit reversal and exposure with response prevention.

    PubMed

    van de Griendt, J M T M; Verdellen, C W J; van Dijk, M K; Verbraak, M J P M

    2013-07-01

    Behaviour therapy has been shown to be an effective strategy in treating tics; both habit reversal (HR) and exposure and response prevention (ER) are recommended as first-line interventions. This review provides an overview of the history, theoretical concepts and evidence at present for HR and ER. In addition, treatment manuals for HR and ER are described. Despite the evidence and availability of treatment manuals, many patients do not receive a first-line psychological intervention for tics. Barriers to the acceptance and dissemination of behaviour therapy are discussed as are ways to overcome these barriers, such as the use of E-health and E-learning.

  5. Antiparasitic Treatment Induces an Improved CD8(+) T Cell Response in Chronic Chagasic Patients.

    PubMed

    Mateus, Jose; Pérez-Antón, Elena; Lasso, Paola; Egui, Adriana; Roa, Nubia; Carrilero, Bartolomé; González, John M; Thomas, M Carmen; Puerta, Concepción J; López, Manuel C; Cuéllar, Adriana

    2017-04-15

    Chagas disease is a chronic infection caused by Trypanosoma cruzi, an intracellular protozoan parasite. Chronic chagasic patients (CCPs) have dysfunctional CD8(+) T cells that are characterized by impaired cytokine production, high coexpression of inhibitory receptors, and advanced cellular differentiation. Most patients diagnosed in the chronic phase of Chagas disease already exhibit heart involvement, and there is no vaccination that protects against the disease. Antiparasitic treatment is controversial as to its indication for this stage of the disease. There is a lack of biological markers to evaluate the effectiveness of antiparasitic treatment, and little is known about the effect of the treatment on CD8(+) T cells. Thus, the aim of the current study was to analyze the early effects of antiparasitic treatment on CD8(+) T cells from CCPs with asymptomatic clinical forms of disease. To evaluate the CD8(+) T cell subsets, expression of inhibitory receptors, and functionality of T cells in CCPs, PBMCs were isolated. The results showed that treatment of CCPs with the asymptomatic form of the disease induces an increase in the frequency of CD8(+) central memory T cells and terminal effector T cells, a decrease in the coexpression of inhibitory receptors, an improved Ag-specific CD8(+) T cell response exhibited by the individual production of IFN-γ or IL-2, and a multifunctional CD8(+) T cell profile of up to four functions (IFN-γ(+)IL-2(+)Perforin(+)Granzyme B(+)). These findings suggest that, in CCPs, antiparasitic treatment improved the quality of Ag-specific CD8(+) T cell responses associated with a decrease in inhibitory receptor coexpression, which could serve as biomarkers for monitoring the effectiveness of antiparasitic treatment.

  6. Baseline characteristics and treatment response of patients from the Philippines in the CHIMES study.

    PubMed

    Navarro, Jose C; Gan, Herminigildo H; Lao, Annabelle Y; Baroque, Alejandro C; Hiyadan, John H B; Chua, Carlos L; San Jose, Ma Cristina; Advincula, Joel M; Lee, Chun Fan; Bousser, Marie-Germaine; Chen, Christopher L H

    2014-10-01

    The CHIMES Study compared MLC601 with placebo in patients with ischemic stroke of intermediate severity in the preceding 72 h. Sites from the Philippines randomized 504 of 1099 (46%) patients in the study. We aimed to define the patient characteristics and treatment responses in this subgroup to better plan future trials. The CHIMES dataset was used to compare the baseline characteristics, time from stroke onset to study treatment initiation, and treatment responses to MLC601 between patients recruited from Philippines and the rest of the cohort. Treatment effect was analyzed using end-points at month 3 as described in the primary publication, that is, modified Rankin Score, National Institutes of Health Stroke Scale, and Barthel Index. The Philippine cohort was younger, had more women, worse baseline National Institutes of Health Stroke Scale, and longer time delay from stroke onset to study treatment compared with the rest of the cohort. Age (P = 0·003), baseline National Institutes of Health Stroke Scale (P < 0·001), and stroke onset to study treatment initiation (P = 0·016) were predictors of modified Rankin Score at three-months. Primary analysis of modified Rankin Score shift was in favor of MLC601 (adjusted odds ratio 1·41, 95% confidence interval 1·01-1·96). Secondary analyses were likewise in favor of MLC601 for modified Rankin Score dichotomy 0-1, improvement in National Institutes of Health Stroke Scale (total and motor scores), and Barthel Index. The treatment effects in the Philippine cohort were in favor of MLC601. This may be due to inclusion of more patients with predictors of poorer outcome. © 2014 The Authors. International Journal of Stroke published by John Wiley & Sons Ltd on behalf of World Stroke Organization.

  7. Influence of Religiosity on 12-Step Participation and Treatment Response Among Substance-Dependent Adolescents*

    PubMed Central

    Kelly, John F.; Pagano, Maria E.; Stout, Robert L.; Johnson, Shannon M.

    2011-01-01

    Objective: Religious practices among adults are associated with more 12-step participation which, in turn, is linked to better treatment outcomes. Despite recommendations for adolescents to participate in mutual-help groups, little is known about how religious practices influence youth 12-step engagement and outcomes. This study examined the relationships among lifetime religiosity, during-treatment 12-step participation, and outcomes among adolescents, and tested whether any observed beneficial relation between higher religiosity and outcome could be explained by increased 12-step participation. Method: Adolescents (n = 195; 52% female, ages 14–18) court-referred to a 2-month residential treatment were assessed at intake and discharge. Lifetime religiosity was assessed with the Religious Background and Behaviors Questionnaire; 12-step assessments measured meeting attendance, step work (General Alcoholics Anonymous Tools of Recovery), and Alcoholics Anonymous (AA)/Narcotics Anonymous (NA)-related helping. Substance-related outcomes and psychosocial outcomes were assessed with toxicology screens, the Adolescent–Obsessive Compulsive Drinking Scale, the Children's Global Assessment Scale, and the Narcissistic Personality Inventory. Results: Greater lifetime formal religious practices at intake were associated with increased step work and AA/NA-related helping during treatment, which in turn were linked to improved substance outcomes, global functioning, and reduced narcissistic entitlement. Increased step work mediated the effect of religious practices on increased abstinence, whereas AA/NA-related helping mediated the effect of religiosity on reduced craving and entitlement. Conclusions: Findings extend the evidence for the protective effects of