Improving quality of care in substance abuse treatment using five key process improvement principles

PubMed Central

Hoffman, Kim A.; Green, Carla A.; Ford, James H.; Wisdom, Jennifer P.; Gustafson, David H.; McCarty, Dennis

2012-01-01

Process and quality improvement techniques have been successfully applied in health care arenas, but efforts to institute these strategies in alcohol and drug treatment are underdeveloped. The Network for the Improvement of Addiction Treatment (NIATx) teaches participating substance abuse treatment agencies to use process improvement strategies to increase client access to, and retention in, treatment. NIATx recommends five principles to promote organizational change: 1) Understand and involve the customer; 2) Fix key problems; 3) Pick a powerful change leader; 4) Get ideas from outside the organization; and 5) Use rapid-cycle testing. Using case studies, supplemented with cross-agency analyses of interview data, this paper profiles participating NIATx treatment agencies that illustrate application of each principle. Results suggest that the most successful organizations integrate and apply most, if not all, of the five principles as they develop and test change strategies. PMID:22282129

Qualitative study of perceived causes of tuberculosis treatment default among health care workers in Morocco.

PubMed

Kizub, D; Ghali, I; Sabouni, R; Bourkadi, J E; Bennani, K; El Aouad, R; Dooley, K E

2012-09-01

In Morocco, tuberculosis (TB) treatment default is increasing in some urban areas. To provide a detailed description of factors that contribute to patient default and solutions from the point of view of health care professionals who participate in TB care. In-depth interviews were conducted with 62 physicians and nurses at nine regional public pulmonary clinics and local health clinics. Participants had a median of 24 years of experience in health care. Treatment default was seen as a result of multilevel factors related to the patient (lack of means, being a migrant worker, distance to treatment site, poor understanding of treatment, drug use, mental illness), medical team (high patient load, low motivation, lack of resources for tracking defaulters), treatment organization (poor communication between treatment sites, no systematic strategy for patient education or tracking, incomplete record keeping), and health care system and society. Tailored recommendations for low- and higher-cost interventions are provided. Interventions to enhance TB treatment completion should take into account the local context and multilevel factors that contribute to default. Qualitative studies involving health care workers directly involved in TB care can be powerful tools to identify contributing factors and define strategies to help reduce treatment default.

Belongingness--The Critical Variable in the Residential Treatment of Alcoholism.

ERIC Educational Resources Information Center

Machell, David F.

Many alcohol treatment programs have stressed a sense of belongingness as a means for successful treatment of alcoholics in a residential setting. An examination of the effectiveness of this strategy in highly structured and less structured programs involved 200 chronic, recidivistic male adult alcoholics in a residential program. Subjects were…

Cost-effectiveness of cervical-cancer screening in five developing countries.

PubMed

Goldie, Sue J; Gaffikin, Lynne; Goldhaber-Fiebert, Jeremy D; Gordillo-Tobar, Amparo; Levin, Carol; Mahé, Cédric; Wright, Thomas C

2005-11-17

Cervical-cancer screening strategies that involve the use of conventional cytology and require multiple visits have been impractical in developing countries. We used computer-based models to assess the cost-effectiveness of a variety of cervical-cancer screening strategies in India, Kenya, Peru, South Africa, and Thailand. Primary data were combined with data from the literature to estimate age-specific incidence and mortality rates for cancer and the effectiveness of screening for and treatment of precancerous lesions. We assessed the direct medical, time, and program-related costs of strategies that differed according to screening test, targeted age and frequency, and number of clinic visits required. Single-visit strategies involved the assumption that screening and treatment could be provided in the same day. Outcomes included the lifetime risk of cancer, years of life saved, lifetime costs, and cost-effectiveness ratios (cost per year of life saved). The most cost-effective strategies were those that required the fewest visits, resulting in improved follow-up testing and treatment. Screening women once in their lifetime, at the age of 35 years, with a one-visit or two-visit screening strategy involving visual inspection of the cervix with acetic acid or DNA testing for human papillomavirus (HPV) in cervical cell samples, reduced the lifetime risk of cancer by approximately 25 to 36 percent, and cost less than 500 dollars per year of life saved. Relative cancer risk declined by an additional 40 percent with two screenings (at 35 and 40 years of age), resulting in a cost per year of life saved that was less than each country's per capita gross domestic product--a very cost-effective result, according to the Commission on Macroeconomics and Health. Cervical-cancer screening strategies incorporating visual inspection of the cervix with acetic acid or DNA testing for HPV in one or two clinical visits are cost-effective alternatives to conventional three-visit cytology-based screening programs in resource-poor settings. Copyright 2005 Massachusetts Medical Society.

A Meta-Analysis of Treatments for Panic Disorder.

ERIC Educational Resources Information Center

Clum, George A.; And Others

1993-01-01

Used metanalysis to compare effectiveness of psychological and pharmacological treatments for panic disorder. Percentage of agoraphobic subjects in sample and duration of illness were unrelated to effect size (ES). Psychological coping strategies involving relaxation training, cognitive restructuring, and exposure yielded most consistent ESs;…

Multilevel Analysis Methods for Partially Nested Cluster Randomized Trials

ERIC Educational Resources Information Center

Sanders, Elizabeth A.

2011-01-01

This paper explores multilevel modeling approaches for 2-group randomized experiments in which a treatment condition involving clusters of individuals is compared to a control condition involving only ungrouped individuals, otherwise known as partially nested cluster randomized designs (PNCRTs). Strategies for comparing groups from a PNCRT in the…

Using Video to Bridge the Gap Between Problem Behavior and a Delayed Time-out Procedure.

PubMed

Coppage, Sara; Meindl, James N

2017-09-01

Treatment plans focused on problem behavior often include punishment contingencies to decrease problem behavior. Immediate punishers are typically more effective than delayed punishers, but immediate delivery of a punisher is not always possible. Strategies need to be developed to increase the suppressive effects of delayed punishers. This study demonstrated the effectiveness of a treatment package involving replaying a video recording of problem behavior immediately before delivering a 15 min delayed time-out. This treatment package may prove to be an accessible and inexpensive strategy when using delayed punishers.

Folliculitis keloidalis nuchae and pseudofolliculitis barbae: are prevention and effective treatment within reach?

PubMed

Alexis, Andrew; Heath, Candrice R; Halder, Rebat M

2014-04-01

Pseudofolliculitis barbae and folliculitis keloidalis nuchae are chronic follicular disorders disproportionately affecting men of African ancestry. This article explores the etiology, pathogenesis, treatment, and prevention strategies of these conditions. Effective treatment and prevention of these disorders involves pharmacologic and procedural interventions as well as behavioral modifications. Copyright © 2014 Elsevier Inc. All rights reserved.

Age-related macular degeneration

PubMed Central

Querques, Giuseppe; Avellis, Fernando Onofrio; Querques, Lea; Bandello, Francesco; Souied, Eric H

2011-01-01

Clinical question: Is there any new knowledge about the pathogenesis and treatment of age-related macular degeneration (AMD)? Results: We now understand better the biochemical and pathological pathways involved in the genesis of AMD. Treatment of exudative AMD is based on intravitreal injection of new antivascular endothelial growth factor drugs for which there does not yet exist a unique recognized strategy of administration. No therapies are actually available for atrophic AMD, despite some experimental new pharmacological approaches. Implementation: strategy of administration, safety of intravitreal injection PMID:21654887

Supplemental Reading Strategy Instruction for Adolescents: A Randomized Trial and Follow-up Study

ERIC Educational Resources Information Center

Cantrell, Susan Chambers; Almasi, Janice F.; Rintamaa, Margaret; Carter, Janis C.

2016-01-01

In this study, the authors examine the impact of a yearlong supplemental reading course involving daily instruction in the learning strategies curriculum on lower achieving adolescent students' reading achievement and motivation. Using a multiple-cohort randomized treatment-control group design over 4 years, they compared achievement and…

Mapping Evidence-Based Treatments for Children and Adolescents: Application of the Distillation and Matching Model to 615 Treatments from 322 Randomized Trials

ERIC Educational Resources Information Center

Chorpita, Bruce F.; Daleiden, Eric L.

2009-01-01

This study applied the distillation and matching model to 322 randomized clinical trials for child mental health treatments. The model involved initial data reduction of 615 treatment protocol descriptions by means of a set of codes describing discrete clinical strategies, referred to as practice elements. Practice elements were then summarized in…

Enhancing treatment for school-age children who stutter II. Reducing bullying through role-playing and self-disclosure.

PubMed

Murphy, William P; Yaruss, J Scott; Quesal, Robert W

2007-01-01

This paper describes several treatment strategies that clinicians can use to help children who stutter who are experiencing bullying and other negative reactions from their peers. Specific strategies include problem-solving activities designed to help the child develop appropriate responses to bullying and a classroom presentation designed to educate peers about stuttering. To facilitate clinicians' application of these techniques, the strategies are presented in the context of a case study involving a 9-year-old boy who participated in a comprehensive treatment program for stuttering. Following treatment, the child exhibited an increased ability to respond to bullying experiences in a constructive fashion. In addition, negative comments by the child's peers diminished following the classroom presentation. Findings suggest that clinicians can help children overcome bullying and other negative reactions associated with stuttering through a number of well-supported treatment strategies that can be applied in a variety of clinical settings. After reading this article, participants will be able to: (1) define bullying and teasing and explain the difference between the two experiences; (2) describe two strategies for helping children who stutter successfully manage bullying experiences at school and in other settings; and (3) explain two strategies for educating children about stuttering and about bullying.

Stepping through treatment: reflections on an adaptive treatment strategy among methamphetamine users with depression.

PubMed

Kay-Lambkin, Frances J; Baker, Amanda L; McKetin, Rebecca; Lee, Nicole

2010-09-01

Stepped-care has been recommended in the alcohol and other drug field and adopted in a number of service settings, but few research projects have examined this approach. This article aims to describe a pilot trial of stepped-care methods in the treatment of methamphetamine use and depression comorbidity. An adaptive treatment strategy was developed based on recommendations for stepped-care among methamphetamine users, and incorporating cognitive behaviour therapy/motivational intervention for methamphetamine use and depression. The adaptive treatment strategy was compared with a fixed treatment, comprising an extended integrated cognitive behaviour therapy/motivational intervention treatment. Eighteen participants across two study sites were involved in the trial, and were current users of methamphetamines (at least once weekly) exhibiting at least moderate symptoms of depression (score of 17 or greater on the Beck Depression Inventory II). Treatment delivered via the adaptive treatment (stepped-care) model was associated with improvement in depression and methamphetamine use, however, was not associated with more efficient delivery of psychological treatment to this population relative to the comparison treatment. This pilot trial attests to the potential for adaptive treatment strategies to increase the evidence base for stepped-care approaches within the alcohol and other drug field. However, in order for stepped-care treatment in this trial to be delivered efficiently, specific training in the delivery and philosophy of the model is required.

Adherence to Treatment in Hypertension.

PubMed

Villalva, Carlos Menéndez; Alvarez-Muiño, Xosé Luís López; Mondelo, Trinidad Gamarra; Fachado, Alfonso Alonso; Fernández, Joaquín Cubiella

2017-01-01

The lack of adherence to treatment in hypertension affects approximately 30 % of patients. The elderly, those with several co-morbidities, social isolation, low incomes or depressive symptoms are the most vulnerable to this problem. There is no ideal method to quantify the adherence to the treatment. Indirect methods are recommended in clinical practice. Any intervention strategy should not blame the patient and try a collaborative approach. It is recommended to involve the patient in decision-making. The clinical interview style must be patient-centered including motivational techniques. The improvement strategies that showed greater effectiveness in the compliance of hypertension treatment were: treatment simplification, appointment reminders systems, blood pressure self-monitoring, organizational improvements and nurse and pharmacists care. The combination of different interventions are recommended against isolated interventions.

The prelude on novel receptor and ligand targets involved in the treatment of diabetes mellitus.

PubMed

Jonnalagadda, Venu Gopal; Ram Raju, Allam Venkata Sita; Pittala, Srinivas; Shaik, Afsar; Selkar, Nilakash Annaji

2014-01-01

Metabolic disorders are a group of disorders, due to the disruption of the normal metabolic process at a cellular level. Diabetes Mellitus and Tyrosinaemia are the majorly reported metabolic disorders. Among them, Diabetes Mellitus is a one of the leading metabolic syndrome, affecting 5 to 7 % of the population worldwide and mainly characterised by elevated levels of glucose and is associated with two types of physiological event disturbances such as impaired insulin secretion and insulin resistance. Up to now, various treatment strategies are like insulin, alphaglucosidase inhibitors, biguanides, incretins were being followed. Concurrently, various novel therapeutic strategies are required to advance the therapy of Diabetes mellitus. For the last few decades, there has been an extensive research in understanding the metabolic pathways involved in Diabetes Mellitus at the cellular level and having the profound knowledge on cell-growth, cell-cycle, and apoptosis at a molecular level provides new targets for the treatment of Diabetes Mellitus. Receptor signalling has been involved in these mechanisms, to translate the information coming from outside. To understand the various receptors involved in these pathways, we must have a sound knowledge on receptors and ligands involved in it. This review mainly summarises the receptors and ligands which are involved the Diabetes Mellitus. Finally, researchers have to develop the alternative chemical moieties that retain their affinity to receptors and efficacy. Diabetes Mellitus being a metabolic disorder due to the glucose surfeit, demands the need for regular exercise along with dietary changes.

Invasive aspergillosis in paediatric oncology patients.

PubMed

Muda, Z; Ibrahim, H; Abdulrahman, E J; Menon, B S; Zahari, Z; Zaleha, A M; Talib, A

2008-12-01

Invasive aspergillosis predominantly occurs in immunocompromised patients and is often resistant to different therapeutically strategies. However, mortality significantly increases if the central nervous system is affected. In this report we describe two cases of invasive aspergilosis, one with kidney involvement with a successful treatment while the other with pulmonary and cerebral involvement with a grave outcome.

Modelling and Optimal Control of Typhoid Fever Disease with Cost-Effective Strategies.

PubMed

Tilahun, Getachew Teshome; Makinde, Oluwole Daniel; Malonza, David

2017-01-01

We propose and analyze a compartmental nonlinear deterministic mathematical model for the typhoid fever outbreak and optimal control strategies in a community with varying population. The model is studied qualitatively using stability theory of differential equations and the basic reproductive number that represents the epidemic indicator is obtained from the largest eigenvalue of the next-generation matrix. Both local and global asymptotic stability conditions for disease-free and endemic equilibria are determined. The model exhibits a forward transcritical bifurcation and the sensitivity analysis is performed. The optimal control problem is designed by applying Pontryagin maximum principle with three control strategies, namely, the prevention strategy through sanitation, proper hygiene, and vaccination; the treatment strategy through application of appropriate medicine; and the screening of the carriers. The cost functional accounts for the cost involved in prevention, screening, and treatment together with the total number of the infected persons averted. Numerical results for the typhoid outbreak dynamics and its optimal control revealed that a combination of prevention and treatment is the best cost-effective strategy to eradicate the disease.

Obesity Treatment: Environment and Behavior Modification.

PubMed

Murphy, Maryanne

2016-09-01

Obesity is commonly encountered in veterinary patients. Although there are various published dietary approaches to achieving weight loss, successful long-term prevention of weight regain has proven elusive. Adding environmental and behavioral treatment strategies to a weight loss plan may help the veterinary team, the pet, and the pet owner maximize the effectiveness of the program. Because the owner directly affects the environment and behavior of the pet undergoing a weight loss plan, treatment strategies with an emphasis on owner involvement is the focus of this review. Veterinary use of the 5 A's behavioral counseling approach with the pet owner is discussed. Copyright © 2016 Elsevier Inc. All rights reserved.

Rehabilitation strategies for partially edentulous-prosthodontic principles and current trends.

PubMed

D'Souza, Dsj; Dua, Parag

2011-07-01

The prosthetic considerations for treatment of partially edentulous patients involve evaluation of important aspects such as presence of certain functional or skeletal deficits, orientation of the occlusal plane, free-way space, size and location of edentulous areas, number, strategic location and quality of the likely abutment teeth, vertical dimension, and the type of occlusion. A comprehensive evaluation, multidisciplinary approach and a sequential treatment plan, worked out in harmony with the patient's perceptions are important factors to ensure a successful outcome. This article discusses the principles, current trends and importance of clinical decisions in designing a treatment strategy when confronted with complex situations of partial edentulism.

Practical tips for sexual counseling and psychotherapy in premature ejaculation.

PubMed

Rowland, David; Cooper, Stewart

2011-10-01

A number of milestones in the treatment of premature ejaculation (PE) have occurred over the past five decades, including the development of various behavioral and cognitive techniques as well as pharmacotherapies that modify neurophysiological processes involved in ejaculation. Nevertheless, the notion that sexual responses such as PE are influenced by physiological, psychobehavioral, cultural, and relationship factors is as valid now as it was 50 years ago, and therefore, interventions should consider all such domains in the development of effective treatment strategies. Provide an overview of which patients with PE are suitable to receive psychosexual treatment and the psychological approaches for managing this disorder. Review of the literature. Psychosexual treatments that integrate behavioral, psychological, and relationship functioning. PE is typically a couple's problem and, therefore, psychotherapy is best when the partner is involved. Before embarking on psychotherapy, the clinician should obtain a medical history pertaining to sexual-, psychological-, and relationship-related factors, so that the treatment strategy can be tailored to the needs of the individual. General strategies underpinning integrative, "process-oriented" elements of psychotherapy most relevant to PE are: developing the therapist-patient relationship; expressing empathy, genuineness, and positive regard; motivational interviewing, i.e., developing motivation to change; developing discrepancy; working through resistance; identifying PE-related affect, cognitions, and behaviors (including interaction with partners); and supporting self-efficacy. The four main domains that encompass psychotherapy techniques specific to the treatment of PE are: behavioral; cognitive; affective; and relational. Sustained positive outcomes in PE may be obtained using a combination treatment strategy that addresses all elements of PE, including psychological and biological factors. Psychosexual treatments may help the patient with PE and his partner to address their sexual problems and improve their overall relationship. The effects of psychosexual therapy may be augmented by combining this intervention with pharmacotherapy. 2011 International Society for Sexual Medicine.

Interventions That Target Criminogenic Needs for Justice-Involved Persons With Serious Mental Illnesses: A Targeted Service Delivery Approach.

PubMed

Wilson, Amy Blank; Farkas, Kathleen; Bonfine, Natalie; Duda-Banwar, Janelle

2018-05-01

This research describes the development of a targeted service delivery approach that tailors the delivery of interventions that target criminogenic needs to the specific learning and treatment needs of justice-involved people with serious mental illnesses (SMIs). This targeted service delivery approach includes five service delivery strategies: repetition and summarizing, amplification, active coaching, low-demand practice, and maximizing participation. Examples of how to apply each strategy in session are provided, as well as recommendations on when to use each strategy during the delivery of interventions that target criminogenic needs. This targeted service delivery approach makes an important contribution to the development of interventions for justice-involved people with SMI by increasing the chances that people with SMI can participate fully in and benefit from these interventions that target criminogenic needs. These developments come at a critical time in the field as the next generation of services for justice-involved people with SMI are being developed.

Game theory and reciprocity in some extensive form experimental games.

PubMed

McCabe, K A; Rassenti, S J; Smith, V L

1996-11-12

We examine decision making in two-person extensive form game trees using nine treatments that vary matching protocol, payoffs, and payoff information. Our objective is to establish replicable principles of cooperative versus noncooperative behavior that involve the use of signaling, reciprocity, and backward induction strategies, depending on the availability of dominated direct punishing strategies and the probability of repeated interaction with the same partner. Contrary to the predictions of game theory, we find substantial support for cooperation under complete information even in various single-play treatments.

Memory Support Strategies and Bundles: A Pathway to Improving Cognitive Therapy for Depression?

PubMed Central

Dong, Lu; Lee, Jason Y.; Harvey, Allison G.

2017-01-01

Objective Therapist use of memory support (MS) alongside treatment-as-usual, with the goal of enhancing patient recall of treatment contents, has been of recent interest as a novel pathway to improve treatment outcome. The Memory Support Intervention involves treatment providers’ using eight specific MS strategies to promote patient memory for treatment. The present study examines to what extent therapist use of MS strategies and bundles improves patient recall of treatment contents and treatment outcome. Methods The data were drawn from a pilot randomized controlled trial reported elsewhere. Participants were 48 adults (mean age = 44.27 years, 29 females) with major depressive disorder (MDD), randomized to receive 14 sessions of either CT+Memory Support (n = 25) or CT-as-usual (n = 23). Therapist use of MS was coded using the Memory Support Rating Scale. Patient memory and treatment outcomes were assessed at baseline, mid-treatment (patient recall only), post-treatment, and 6-month follow-up. Results Participants in CT+Memory Support received significantly higher amount of MS relative to CT-as-usual. Though not reaching statistical significance, small-to-medium effects were observed between MS strategies and patient recall in the expected direction. Although MS variables were not significantly associated with changes in continuous depressive symptoms, MS was associated with better global functioning. MS also exhibited small to medium effects on treatment response and recurrence in the expected direction but not on remission, though these effects did not reach statistical significance. Conclusions These results provide initial empirical evidence supporting an active method for therapists to implement MS strategies. PMID:28221056

Family-focused physical activity, diet and obesity interventions in African-American girls: a systematic review.

PubMed

Barr-Anderson, D J; Adams-Wynn, A W; DiSantis, K I; Kumanyika, S

2013-01-01

Obesity interventions that involve family members may be effective with racial/ethnic minority youth. This review assessed the nature and effectiveness of family involvement in obesity interventions among African-American girls aged 5-18 years, a population group with high rates of obesity. Twenty-six databases were searched between January 2011 and March 2012, yielding 27 obesity pilot or full-length prevention or treatment studies with some degree of family involvement and data specific to African-American girls. Interventions varied in type and level of family involvement, cultural adaptation, delivery format and behaviour change intervention strategies; most targeted parent-child dyads. Some similarities in approach based on family involvement were identified. The use of theoretical perspectives specific to African-American family dynamics was absent. Across all studies, effects on weight-related behaviours were generally promising but often non-significant. Similar conclusions were drawn for weight-related outcomes among the full-length randomized controlled trials. Many strategies appeared promising on face value, but available data did not permit inferences about whether or how best to involve family members in obesity prevention and treatment interventions with African-American girls. Study designs that directly compare different types and levels of family involvement and incorporate relevant theoretical elements may be an important next step. © 2012 The Authors. obesity reviews © 2012 International Association for the Study of Obesity.

Isolating active ingredients in a parent-mediated social communication intervention for toddlers with autism spectrum disorder.

PubMed

Gulsrud, Amanda C; Hellemann, Gerhard; Shire, Stephanie; Kasari, Connie

2016-05-01

Behavioral interventions are commonplace in the treatment of autism spectrum disorders, yet relatively little is known about how and why these interventions work. This study tests the relationship between isolated core components of a packaged social communication intervention and the primary outcome, joint engagement, to better understand how the intervention is affecting change in individuals. A total of 86 toddlers and their parents were enrolled in the study and randomized to one of two treatments, the joint attention, symbolic play, engagement, and regulation (JASPER) parent-mediated intervention or a psychoeducational intervention. Measures regarding the parent's use of intervention strategies were collected before and after the 10-week intervention. Additional measures of child and parent joint engagement were also collected. A significant effect of treatment was found for all four of the core strategies of the intervention, favoring a larger increase in the JASPER condition. A hierarchical linear regression revealed several individual predictors of joint engagement, including parent-rated buy-in, interventionist-rated parent involvement, and parental use of strategies. To complement the hierarchical analysis, we also tested the potential mediating effect the strategies may have on the relationship between treatment and joint engagement. Results showed that the strategy of mirrored pacing mediated the relationship between treatment and joint engagement in the positive direction. These results strongly suggest that the mirrored pacing strategy is an active ingredient of the JASPER treatment. © 2015 Association for Child and Adolescent Mental Health.

Public involvement in the priority setting activities of a wait time management initiative: a qualitative case study.

PubMed

Bruni, Rebecca A; Laupacis, Andreas; Levinson, Wendy; Martin, Douglas K

2007-11-16

As no health system can afford to provide all possible services and treatments for the people it serves, each system must set priorities. Priority setting decision makers are increasingly involving the public in policy making. This study focuses on public engagement in a key priority setting context that plagues every health system around the world: wait list management. The purpose of this study is to describe and evaluate priority setting for the Ontario Wait Time Strategy, with special attention to public engagement. This study was conducted at the Ontario Wait Time Strategy in Ontario, Canada which is part of a Federal-Territorial-Provincial initiative to improve access and reduce wait times in five areas: cancer, cardiac, sight restoration, joint replacements, and diagnostic imaging. There were two sources of data: (1) over 25 documents (e.g. strategic planning reports, public updates), and (2) 28 one-on-one interviews with informants (e.g. OWTS participants, MOHLTC representatives, clinicians, patient advocates). Analysis used a modified thematic technique in three phases: open coding, axial coding, and evaluation. The Ontario Wait Time Strategy partially meets the four conditions of 'accountability for reasonableness'. The public was not directly involved in the priority setting activities of the Ontario Wait Time Strategy. Study participants identified both benefits (supporting the initiative, experts of the lived experience, a publicly funded system and sustainability of the healthcare system) and concerns (personal biases, lack of interest to be involved, time constraints, and level of technicality) for public involvement in the Ontario Wait Time Strategy. Additionally, the participants identified concern for the consequences (sustainability, cannibalism, and a class system) resulting from the Ontario Wait Times Strategy. We described and evaluated a wait time management initiative (the Ontario Wait Time Strategy) with special attention to public engagement, and provided a concrete plan to operationalize a strategy for improving public involvement in this, and other, wait time initiatives.

Public involvement in the priority setting activities of a wait time management initiative: a qualitative case study

PubMed Central

Bruni, Rebecca A; Laupacis, Andreas; Levinson, Wendy; Martin, Douglas K

2007-01-01

Background As no health system can afford to provide all possible services and treatments for the people it serves, each system must set priorities. Priority setting decision makers are increasingly involving the public in policy making. This study focuses on public engagement in a key priority setting context that plagues every health system around the world: wait list management. The purpose of this study is to describe and evaluate priority setting for the Ontario Wait Time Strategy, with special attention to public engagement. Methods This study was conducted at the Ontario Wait Time Strategy in Ontario, Canada which is part of a Federal-Territorial-Provincial initiative to improve access and reduce wait times in five areas: cancer, cardiac, sight restoration, joint replacements, and diagnostic imaging. There were two sources of data: (1) over 25 documents (e.g. strategic planning reports, public updates), and (2) 28 one-on-one interviews with informants (e.g. OWTS participants, MOHLTC representatives, clinicians, patient advocates). Analysis used a modified thematic technique in three phases: open coding, axial coding, and evaluation. Results The Ontario Wait Time Strategy partially meets the four conditions of 'accountability for reasonableness'. The public was not directly involved in the priority setting activities of the Ontario Wait Time Strategy. Study participants identified both benefits (supporting the initiative, experts of the lived experience, a publicly funded system and sustainability of the healthcare system) and concerns (personal biases, lack of interest to be involved, time constraints, and level of technicality) for public involvement in the Ontario Wait Time Strategy. Additionally, the participants identified concern for the consequences (sustainability, cannibalism, and a class system) resulting from the Ontario Wait Times Strategy. Conclusion We described and evaluated a wait time management initiative (the Ontario Wait Time Strategy) with special attention to public engagement, and provided a concrete plan to operationalize a strategy for improving public involvement in this, and other, wait time initiatives. PMID:18021393

Conceptual change strategies in teaching genetics

NASA Astrophysics Data System (ADS)

Batzli, Laura Elizabeth

The purpose of this study was to evaluate the effectiveness of utilizing conceptual change strategies when teaching high school genetics. The study examined the effects of structuring instruction to provide students with cognitive situations which promote conceptual change, specifically instruction was structured to elicit students' prior knowledge. The goal of the study was that the students would not only be able to solve genetics problems and define basic terminology but they would also have constructed more scientific schemas of the actual processes involved in inheritance. This study is based on the constructivist theory of learning and conceptual change research which suggest that students are actively involved in the process of relating new information to prior knowledge as they construct new knowledge. Two sections of biology II classes received inquiry based instruction and participated in structured cooperative learning groups. However, the unique difference in the treatment group's instruction was the use of structured thought time and the resulting social interaction between the students. The treatment group students' instructional design allowed students to socially construct their cognitive knowledge after elicitation of their prior knowledge. In contrast, the instructional design for the control group students allowed them to socially construct their cognitive knowledge of genetics without the individually structured thought time. The results indicated that the conceptual change strategies with individually structured thought time improved the students' scientific mastery of genetics concepts and they maintained fewer post instructional alternative conceptions. Although all students gained the ability to correctly solve genetics problems, the treatment group students were able to explain the processes involved in terms of meiosis. The treatment group students were also able to better apply their knowledge to novel genetic situations. The implications for genetics instruction from these results were discussed.

A Protocol for the Assessment and Treatment of School Phobia.

ERIC Educational Resources Information Center

Doll, Beth

This paper addresses the problem of school phobia, one of the most common childhood anxiety disorders. It presents four case studies of preadolescent school phobia involving two girls and two boys in grades four through seven. Several features of effective strategies for the assessment and treatment of school phobia which have emerged from the…

The Effect of a Multiple Treatment Program and Maintenance Procedures on Smoking Cessation.

ERIC Educational Resources Information Center

Powell, Don R.

The efficacy of a multiple treatment smoking cessation program and three maintenance strategies was evaluated. Phases I and II of the study involved 51 subjects who participated in a five-day smoking cessation project consisting of lectures, demonstrations, practice exercises, negative smoking, and the teaching of self-control procedures. At the…

Parental Factors that Detract from the Effectiveness of Cognitive-Behavioral Treatment for Childhood Anxiety: Recommendations for Practitioners

ERIC Educational Resources Information Center

Walker, Jerry V., III

2012-01-01

This article reviews the recent empirical literature on the various parental factors that detract from the effectiveness of cognitive-behavioral treatment for children with anxiety. Interventions such as treating parental anxiety and increasing parental involvement in the therapeutic process may combat these factors. Newer strategies such as…

Memory support strategies and bundles: A pathway to improving cognitive therapy for depression?

PubMed

Dong, Lu; Lee, Jason Y; Harvey, Allison G

2017-03-01

Therapist use of memory support (MS) alongside treatment-as-usual, with the goal of enhancing patient recall of treatment contents, has been of recent interest as a novel pathway to improve treatment outcome. The memory support intervention (MSI) involves treatment providers' using 8 specific MS strategies to promote patient memory for treatment. The present study examines to what extent therapist use of MS strategies and bundles improves patient recall of treatment contents and treatment outcome. The data were drawn from a pilot RCT reported elsewhere. Participants were 48 adults (mean age = 44.27 years, 29 females) with major depressive disorder (MDD), randomized to receive 14 sessions of either CT + Memory Support (n = 25) or CT-as-usual (n = 23). Therapist use of MS was coded using the Memory Support Rating Scale. Patient memory and treatment outcomes were assessed at baseline, midtreatment (patient recall only), posttreatment, and 6-month follow-up. Participants in CT + Memory Support received significantly higher amount of MS relative to CT-as-usual. Although not reaching statistical significance, small-to-medium effects were observed between MS strategies and patient recall in the expected direction. Although MS variables were not significantly associated with changes in continuous depressive symptoms, MS was associated with better global functioning. MS also exhibited small to medium effects on treatment response and recurrence in the expected direction but not on remission, though these effects did not reach statistical significance. These results provide initial empirical evidence supporting an active method for therapists to implement MS strategies. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Autonomic nervous system involvement in pulmonary arterial hypertension.

PubMed

Vaillancourt, Mylène; Chia, Pamela; Sarji, Shervin; Nguyen, Jason; Hoftman, Nir; Ruffenach, Gregoire; Eghbali, Mansoureh; Mahajan, Aman; Umar, Soban

2017-12-04

Pulmonary arterial hypertension (PAH) is a chronic pulmonary vascular disease characterized by increased pulmonary vascular resistance (PVR) leading to right ventricular (RV) failure. Autonomic nervous system involvement in the pathogenesis of PAH has been demonstrated several years ago, however the extent of this involvement is not fully understood. PAH is associated with increased sympathetic nervous system (SNS) activation, decreased heart rate variability, and presence of cardiac arrhythmias. There is also evidence for increased renin-angiotensin-aldosterone system (RAAS) activation in PAH patients associated with clinical worsening. Reduction of neurohormonal activation could be an effective therapeutic strategy for PAH. Although therapies targeting adrenergic receptors or RAAS signaling pathways have been shown to reverse cardiac remodeling and improve outcomes in experimental pulmonary hypertension (PH)-models, the effectiveness and safety of such treatments in clinical settings have been uncertain. Recently, novel direct methods such as cervical ganglion block, pulmonary artery denervation (PADN), and renal denervation have been employed to attenuate SNS activation in PAH. In this review, we intend to summarize the multiple aspects of autonomic nervous system involvement in PAH and overview the different pharmacological and invasive strategies used to target autonomic nervous system for the treatment of PAH.

Facilitating Mental Health Service Use for Caregivers: Referral Strategies among Child Welfare Caseworkers.

PubMed

Bunger, Alicia C; Chuang, Emmeline; McBeath, Bowen

2012-04-01

Unmet needs for mental health care are common among caregivers involved in the child welfare system. Although child welfare caseworkers are well positioned to identify service needs and refer caregivers to treatment, little is known about the types of referral strategies used in practice, or their effectiveness for promoting mental health service use. The current study examined child welfare caseworkers' use of different referral strategies and the extent to which these strategies are associated with caregivers' receipt of mental health services within a national sample of child welfare cases. Analyses of the second cohort of families from the National Survey of Child and Adolescent Well-Being suggest that child welfare workers more often use informational strategies for referring caregivers, including suggesting treatment or providing information about treatment options. However, social referral strategies such as providing caregivers with direct assistance in completing applications and making and attending appointments were associated with a greater likelihood of caregivers receiving mental health services. Findings support evidence from other service contexts that service use is facilitated by caseworkers' direct support for arranging services. Implications for research and for child welfare managers and administrators are discussed.

Considering patient values and treatment preferences enhances patient involvement in rectal cancer treatment decision making.

PubMed

Kunneman, Marleen; Marijnen, Corrie A M; Baas-Thijssen, Monique C M; van der Linden, Yvette M; Rozema, Tom; Muller, Karin; Geijsen, Elisabeth D; Stiggelbout, Anne M; Pieterse, Arwen H

2015-11-01

The shared decision making (SDM) model states that patients' values and preferences should be clarified to choose a strategy that best fits the patient. This study aimed to assess whether values and preferences of rectal cancer patients are voiced and considered in deciding about preoperative radiotherapy (PRT), and whether this makes patients feel more involved in treatment decision making. Pre-treatment consultations of radiation oncologists and patients eligible for PRT were audiotaped (N=90). Tapes were transcribed and coded to identify patients' values and treatment preferences. Patients filled in a post-consultation questionnaire on their perceived involvement in decision making (N=60). Patients' values were voiced for 62/611 of benefits/harms addressed (10%), in 38/90 consultations (42%; maximum 4 values per consultation), and most often related to major long-term treatment outcomes. Patients' treatment preferences were discussed in 20/90 consultations (22%). In 16/90 consultations (18%), the oncologists explicitly indicated to consider patients' values or preferences. Patients perceived a significantly more active role in decision making if their values or preferences had been voiced or considered. Patients' values and treatment preferences are voiced or considered in a minority of consultations. If they are, this increases patients' perceived involvement in the decision making process. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Strategies for Involvement in Wildlife Issues.

ERIC Educational Resources Information Center

Kennedy, Carolyn L.; Nye, Donna I.

1984-01-01

Highlights a workshop with children focusing on the treatment of controversial issues and guidelines typically provided by school districts or organizations. Activities designed to stimulate discussion on three issues (endangered species, acid rain, and predator control) are included. (BC)

High-risk adolescents and satanic cults.

PubMed

Ahmed, M B

1991-10-01

During the last decade the number of teenagers involved in violent behavior and drug abuse increased significantly. Some of these adolescents were involved in Satanic cult activities. Although sensationalism is created by isolated incidents like the Matamoros murders and Geraldo's media coverage of satanism, our observation, in a private psychiatric hospital, reveals that in fact adolescents involved in satanic cults do not differ from other adolescents admitted with a variety of other problems. Psychodynamic factors, family dynamics, and treatment strategies for management of adolescents who are involved in satanic cult activities are discussed.

Two strategies for phosphorus removal from reject water of municipal wastewater treatment plant using alum sludge.

PubMed

Yang, Y; Zhao, Y Q; Babatunde, A O; Kearney, P

2009-01-01

In view of the well recognized need of reject water treatment in MWWTP (municipal wastewater treatment plant), this paper outlines two strategies for P removal from reject water using alum sludge, which is produced as by-product in drinking water treatment plant when aluminium sulphate is used for flocculating raw waters. One strategy is the use of the alum sludge in liquid form for co-conditioning and dewatering with the anaerobically digested activated sludge in MWWTP. The other strategy involves the use of the dewatered alum sludge cakes in a fixed bed for P immobilization from the reject water that refers to the mixture of the supernatant of the sludge thickening process and the supernatant of the anaerobically digested sludge. Experimental trials have demonstrated that the alum sludge can efficiently reduce P level in reject water. The co-conditioning strategy could reduce P from 597-675 mg P/L to 0.14-3.20 mg P/L in the supernatant of the sewage sludge while the organic polymer dosage for the conditioning of the mixed sludges would also be significantly reduced. The second strategy of reject water filtration with alum sludge bed has shown a good performance of P reduction. The alum sludge has P-adsorption capacity of 31 mg-P/g-sludge, which was tested under filtration velocity of 1.0 m/h. The two strategies highlight the beneficial utilization of alum sludge in wastewater treatment process in MWWTP, thus converting the alum sludge as a useful material, rather than a waste for landfill.

Therapeutic strategies in severe neuropsychiatric systemic lupus erythematosus: experience from a tertiary referral centre.

PubMed

Bortoluzzi, A; Padovan, M; Farina, I; Galuppi, E; De Leonardis, F; Govoni, M

2012-12-20

The management of neuropsychiatric systemic lupus erythematosus (NPSLE) still remains empirical and based on clinical experience due to the lack of randomized controlled trials. To report the experience accumulated in a single tertiary referral centre about treatment of severe cases of NPSLE patients and to discuss therapeutic strategies on the background of EULAR recommendations. Retrospective analysis of all consecutive cases of severe NPSLE treated in our centre since 1990 to 2010, satisfying the 1999 ACR criteria. Among 633 SLE patients who consecutively attended our centre, 231 (36%) displayed at least one neuropsychiatric (NP) manifestation for a total of 408 events attributable to SLE. Thirty-one patients (4.8%), 27 females and 4 males, experienced 35 major NP events requiring immunosuppressive therapy (including 3 relapses and 1 new event). An aggressive immunosuppressive strategy was applied to those patients with an immune mediated inflammatory NP event and to those patients with an increased disease activity as judged by ECLAM and SLEDAI scores. Overall at the end of the therapy 74% of the patients reached clinical remission or significant improvement of their symptoms measured by mean SLEDAI (from 10.09 ± 1.09 to 2.04 ± 0.52, P<0.0001) and ECLAM (from 4 ± 0.34 to 1.38 ± 0.37, P<0.001) scores. The prevalence of NP involvement, described in our case series, is similar to those reported in literature as well as the treatment strategies applied. Nowadays, it is not possible to establish a standardized approach for each single NPSLE manifestation, and different therapeutic strategies must be tailored taking into account the most probable pathogenic mechanism involved, the general disease activity background, the co-morbidities, the type and the stage of the systemic involvement.

Female urinary incontinence: effective treatment strategies.

PubMed

Castro, R A; Arruda, R M; Bortolini, M A T

2015-04-01

Urinary incontinence is a dysfunction that tremendously affects women's quality of life, involving social, emotional and economic aspects. Although various treatments for urinary incontinence have been described, it is important to know which of them are truly effective. This review seeks to determine the current available therapies for women with stress urinary incontinence and overactive bladder syndrome, based on the best scientific evidence.

Prefrontal Cortex and Drug Abuse Vulnerability: Translation to Prevention and Treatment Interventions

PubMed Central

Perry, Jennifer L.; Joseph, Jane E.; Jiang, Yang; Zimmerman, Rick S.; Kelly, Thomas H.; Darna, Mahesh; Huettl, Peter; Dwoskin, Linda P.; Bardo, Michael T.

2010-01-01

Vulnerability to drug abuse is related to both reward seeking and impulsivity, two constructs thought to have a biological basis in the prefrontal cortex (PFC). This review addresses similarities and differences in neuroanatomy, neurochemistry and behavior associated with PFC function in rodents and primates. Emphasis is placed on monoamine and amino acid neurotransmitter systems located in anatomically distinct subregions: medial prefrontal cortex (mPFC); lateral prefrontal cortex (lPFC); anterior cingulate cortex (ACC); and orbitofrontal cortex (OFC). While there are complex interconnections and overlapping functions among these regions, each is thought to be involved in various functions related to health-related risk behaviors and drug abuse vulnerability. Among the various functions implicated, evidence suggests that mPFC is involved in reward processing, attention and drug reinstatement; lPFC is involved in decision-making, behavioral inhibition and attentional gating; ACC is involved in attention, emotional processing and self-monitoring; and OFC is involved in behavioral inhibition, signaling of expected outcomes and reward/punishment sensitivity. Individual differences factors (e.g., age and sex) influence functioning of these regions, which, in turn, impacts drug abuse vulnerability. Implications for the development of drug abuse prevention and treatment strategies aimed at engaging PFC inhibitory processes that may reduce risk-related behaviors are discussed, including the design of effective public service announcements, cognitive exercises, physical activity, direct current stimulation, feedback control training and pharmacotherapies. A major challenge in drug abuse prevention and treatment rests with improving intervention strategies aimed at strengthening PFC inhibitory systems among at-risk individuals. PMID:20837060

Strategic threat management: an exploration of nursing strategies in the pediatric intensive care unit.

PubMed

Durso, Francis T; Ferguson, Ashley N; Kazi, Sadaf; Cunningham, Charlene; Ryan, Christina

2015-03-01

Part of the work of a critical care nurse is to manage the threats that arise that could impede efficient and effective job performance. Nurses manage threats by employing various strategies to keep performance high and workload manageable. We investigated strategic threat management by using the Threat-Strategy Interview. Threats frequently involved technology, staff, or organizational components. The threats were managed by a toolbox of multifaceted strategies, the most frequent of which involved staff-, treatment- (patient + technology), examination- (patient + clinician), and patient-oriented strategies. The profile of strategies for a particular threat often leveraged work facets similar to the work facet that characterized the threat. In such cases, the nurse's strategy was directed at eliminating the threat (not working around it). A description at both a domain invariant level - useful for understanding strategic threat management generally - and a description at an operational, specific level - useful for guiding interventions-- are presented. A structural description of the relationship among threats, strategies, and the cues that trigger them is presented in the form of an evidence accumulation framework of strategic threat management. Copyright © 2014 Elsevier Ltd and The Ergonomics Society. All rights reserved.

Cost Effectiveness of Candida Polymerase Chain Reaction Detection and Empirical Antifungal Treatment among Patients with Suspected Fungal Peritonitis in the Intensive Care Unit.

PubMed

Pagès, Arnaud; Iriart, Xavier; Molinier, Laurent; Georges, Bernard; Berry, Antoine; Massip, Patrice; Juillard-Condat, Blandine

2017-12-01

Mortality from intra-abdominal candidiasis in intensive care units (ICUs) is high. It takes many days for peritoneal-fluid fungal culture to become positive, and the recommended empirical antifungal therapy involves excessive costs. Polymerase chain reaction (PCR) should produce results more rapidly than fungal culture. To perform a cost-effectiveness analysis of the combination of several diagnostic and therapeutic strategies to manage Candida peritonitis in non-neutropenic adult patients in ICUs. We constructed a decision tree model to evaluate the cost effectiveness. Cost and effectiveness were taken into account in a 1-year time horizon and from the French National Health Insurance perspective. Six strategies were compared: fluconazole or echinocandin as an empirical therapy, plus diagnosis by fungal culture or detection by PCR of all Candida species, or use of PCR to detect most fluconazole-resistant Candida species (i.e., Candida krusei and Candida glabrata). The use of fluconazole empirical treatment and PCR to detect all Candida species is more cost effective than using fluconazole empirical treatment without PCR (incremental cost-effectiveness ratio of €40,055/quality-adjusted life-year). Empirical treatment with echinocandin plus PCR to detect C. krusei and C. glabrata is the most effective strategy, but has an incremental cost-effectiveness ratio of €93,776/quality-adjusted life-year. If the cost of echinocandin decreases, then strategies involving PCR plus empirical echinocandin become more cost-effective. Detection by PCR of all Candida species and of most fluconazole-resistant Candida species could improve the cost-effectiveness of fluconazole and echinocandin given to non-neutropenic patients with suspected peritoneal candidiasis in ICUs. Copyright © 2017 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

Structure and Ligand Based Drug Design Strategies in the Development of Novel 5-LOX Inhibitors

PubMed Central

Aparoy, Polamarasetty; Kumar Reddy, Kakularam; Reddanna, Pallu

2012-01-01

Lipoxygenases (LOXs) are non-heme iron containing dioxygenases involved in the oxygenation of polyunsaturated fatty acids (PUFAs) such as arachidonic acid (AA). Depending on the position of insertion of oxygen, LOXs are classified into 5-, 8-, 9-, 12- and 15-LOX. Among these, 5-LOX is the most predominant isoform associated with the formation of 5-hydroperoxyeicosatetraenoic acid (5-HpETE), the precursor of non-peptido (LTB4) and peptido (LTC4, LTD4, and LTE4) leukotrienes. LTs are involved in inflammatory and allergic diseases like asthma, ulcerative colitis, rhinitis and also in cancer. Consequently 5-LOX has become target for the development of therapeutic molecules for treatment of various inflammatory disorders. Zileuton is one such inhibitor of 5-LOX approved for the treatment of asthma. In the recent times, computer aided drug design (CADD) strategies have been applied successfully in drug development processes. A comprehensive review on structure based drug design strategies in the development of novel 5-LOX inhibitors is presented in this article. Since the crystal structure of 5-LOX has been recently solved, efforts to develop 5-LOX inhibitors have mostly relied on ligand based rational approaches. The present review provides a comprehensive survey on these strategies in the development of 5-LOX inhibitors. PMID:22680930

Designing an implementation strategy to improve interprofessional shared decision making in sciatica: study protocol of the DISC study.

PubMed

Hofstede, Stefanie N; Marang-van de Mheen, Perla J; Assendelft, Willem J J; Vleggeert-Lankamp, Carmen L A; Stiggelbout, Anne M; Vroomen, Patrick C A J; van den Hout, Wilbert B; Vliet Vlieland, Thea P M; van Bodegom-Vos, Leti

2012-06-15

Sciatica is a common condition worldwide that is characterized by radiating leg pain and regularly caused by a herniated disc with nerve root compression. Sciatica patients with persisting leg pain after six to eight weeks were found to have similar clinical outcomes and associated costs after prolonged conservative treatment or surgery at one year follow-up. Guidelines recommend that the team of professionals involved in sciatica care and patients jointly decide about treatment options, so-called interprofessional shared decision making (SDM). However, there are strong indications that SDM for sciatica patients is not integrated in daily practice. We designed a study aiming to explore the barriers and facilitators associated with the everyday embedding of SDM for sciatica patients. All related relevant professionals and patients are involved to develop a tailored strategy to implement SDM for sciatica patients. The study consists of two phases: identification of barriers and facilitators and development of an implementation strategy. First, barriers and facilitators are explored using semi-structured interviews among eight professionals of each (para)medical discipline involved in sciatica care (general practitioners, physical therapists, neurologists, neurosurgeons, and orthopedic surgeons). In addition, three focus groups will be conducted among patients. Second, the identified barriers and facilitators will be ranked using a questionnaire among a representative Dutch sample of 200 GPs, 200 physical therapists, 200 neurologists, all 124 neurosurgeons, 200 orthopedic surgeons, and 100 patients. A tailored team-based implementation strategy will be developed based on the results of the first phase using the principles of intervention mapping and an expert panel. Little is known about effective strategies to increase the uptake of SDM. Most implementation strategies only target a single discipline, whereas multiple disciplines are involved in SDM among sciatica patients. The results of this study can be used as an example for implementing SDM in other patient groups receiving multidisciplinary complex care (e.g., elderly) and can be generalized to other countries with similar context, thereby contributing to a worldwide increase of SDM in preference sensitive choices.

Conflict and user involvement in drug misuse treatment decision-making: a qualitative study

PubMed Central

Fischer, Jan; Neale, Joanne; Bloor, Michael; Jenkins, Nicholas

2008-01-01

Background This paper examines client/staff conflict and user involvement in drug misuse treatment decision-making. Methods Seventy-nine in-depth interviews were conducted with new treatment clients in two residential and two community drug treatment agencies. Fifty-nine of these clients were interviewed again after twelve weeks. Twenty-seven interviews were also conducted with staff, who were the keyworkers for the interviewed clients. Results Drug users did not expect, desire or prepare for conflict at treatment entry. They reported few actual conflicts within the treatment setting, but routinely discussed latent conflicts – that is, negative experiences and problematic aspects of current or previous treatment that could potentially escalate into overt disputes. Conflict resulted in a number of possible outcomes, including the premature termination of treatment; staff deciding on the appropriate outcome; the client appealing to the governance structure of the agency; brokered compromise; and staff skilfully eliciting client consent for staff decisions. Conclusion Although the implementation of user involvement in drug treatment decision-making has the potential to trigger high levels of staff-client conflict, latent conflict is more common than overt conflict and not all conflict is negative. Drug users generally want to be co-operative at treatment entry and often adopt non-confrontational forms of covert resistance to decisions about which they disagree. Staff sometimes deploy user involvement as a strategy for managing conflict and soliciting client compliance to treatment protocols. Suggestions for minimising and avoiding harmful conflict in treatment settings are given. PMID:18837989

The management of patients with limited-stage classical Hodgkin lymphoma.

PubMed

Gospodarowicz, Mary K; Meyer, Ralph M

2006-01-01

The term limited-stage Hodgkin lymphoma refers to those patients with stage I-II disease and an absence of bulky disease. Among those patients with classical Hodgkin lymphoma, approximately one-third of patients will fall into this category. As long-term disease control can now be anticipated in more than 90% of these patients, management strategies must increasingly address the need to reduce the long-term treatment-related risks. Current treatment options include use of combined modality therapy that includes an abbreviated course of chemotherapy and involved-field radiation or treatment with chemotherapy, currently consisting of ABVD, as a single modality. The choice of treatment between these two options involves specific trade-offs that must balance issues of disease control against long-term risk of late effects.

Diagnosis, treatment, clinical course, and prognosis of childhood-onset craniopharyngioma patients.

PubMed

Müller, Hermann L

2017-12-01

For decades gross-total resection was the preferred treatment option in childhood-onset craniopharyngioma, assuming that radical strategies at the time of initial diagnosis and treatment would result in cure. Recent reports on long-term prognosis, novel treatment approaches, and molecular genetics provide new insights into more risk-adapted treatment strategies in order to prevent sequelae such as hypothalamic syndrome. A search for original articles published between 2000 and 2016 was performed in PubMed, Science Citation Index Expanded, EMBASE and Scopus. The search terms used were "craniopharyngioma", "hypothalamus", "pituitary", "obesity", "irradiation", and "neurosurgery". The clinical, neuroradiological and surgical definition of hypothalamic involvement is a fundamental factor related to postoperative poor outcome, progressive obesity and neuropsychological impairment after surgical removal. There is a need to change the previous "gold-standard" objective of a primary radical tumor removal in all cases by the new paradigm of a limited resection plus focused radiotherapy in patients with hypothalamic lesions. Hypothalamic involvement and treatment-related hypothalamic lesions are associated with the highest risk of postoperative sequelae. Three dimensional intensity modulated proton beam radiotherapy has potential advantage of over photon beam methods to focus and limit the radiation effects to optic and hypothalamic structures. Preclinical, in vivo mouse models of craniopharyngioma have potential advantage to investigate molecular pathways deregulated in the tumor and to test the use of specific drugs. As expertise has been shown to have impact on post-treatment morbidity, medical societies should establish criteria of adequate professional expertise for the treatment of craniopharyngioma.

Increasing patient involvement in choosing treatment for early breast cancer.

PubMed

Street, R L; Voigt, B; Geyer, C; Manning, T; Swanson, G P

1995-12-01

This investigation examined factors affecting patient involvement in consultations to decide local treatment for early breast cancer and the effectiveness of two methods of preconsultation education aimed at increasing patient participation in these discussions. Sixty patients with Stage I or II breast cancer (1) were pretested on their knowledge about breast cancer treatment and optimism for the future, (2) were randomly assigned to one of two methods for preconsultation education: interactive multimedia program or brochure, (3) completed knowledge and optimism measures, (4) consulted with a medical oncologist, radiation oncologist, and general surgeon, and (5) completed self-report measures assessing their involvement in the consultations and control over decision-making. The consultations were audiorecorded and analyzed to identify behavioral indicators of patient involvement (question-asking, opinion-giving, and expressing concern) and physician utterances encouraging patient participation. College-educated patients younger than 65 years of age were more active participants in these consultations than were older, less educated patients. In addition, patients showed more involvement when they interacted with physicians who encouraged and facilitated patient participation. The method of education did not affect patient involvement although patients tended to learn more about breast cancer treatment after using the multimedia program than after reading the brochure. Although patients vary in their expressiveness, physicians may be able to increase patient participation in deciding treatment by using patient-centered behavior. Also, preconsultation education appears to be an effective clinical strategy for helping patients gain an accurate understanding of their treatment options before meeting with physicians.

The Marathi "taskonomy" of respiratory illnesses in children.

PubMed

Chand, A D; Bhattacharyya, K

1994-05-01

The reduction of childhood mortality from respiratory infections depends upon a case management strategy which encourages the decision to seek treatment. The research discussed, conducted in Pachod, Maharashtra, India, uses a "taskonomic" approach to understanding the diagnosis of illness and treatment decisions. This approach views treatment decisions as a result not only of local conceptual models of illness, but also of the specific circumstances of illness episodes involving different types of social relationships and control over resources.

Management of impulse control disorders in Parkinson's disease: Controversies and future approaches.

PubMed

Samuel, Michael; Rodriguez-Oroz, Maria; Antonini, Angelo; Brotchie, Jonathan M; Ray Chaudhuri, Kallol; Brown, Richard G; Galpern, Wendy R; Nirenberg, Melissa J; Okun, Michael S; Lang, Anthony E

2015-02-01

Impulse control disorders in Parkinson's disease are a group of impulsive behaviors most often associated with dopaminergic treatment. Presently, there is a lack of high quality evidence available to guide their management. This manuscript reviews current management strategies, before concentrating on the concept of dopamine agonist withdrawal syndrome and its implications for the management of impulse control disorders. Further, we focus on controversies, including the role of more recently available anti-parkinsonian drugs, and potential future approaches involving routes of drug delivery, nonpharmacological treatments (such as cognitive behavioral therapy and deep brain stimulation), and other as yet experimental strategies. © 2015 International Parkinson and Movement Disorder Society.

Impulse Control Disorders in Parkinson’s Disease:Management, Controversies, and Potential Approaches

PubMed Central

Samuel, M; Rodriguez-Oroz, M; Antonini, A; Brotchie, JM; Ray Chaudhuri, K; Brown, RG; Galpern, WR; Nirenberg, MJ; Okun, MS; Lang, AE

2016-01-01

Impulse control disorders in Parkinson’s disease are a group of impulsive behaviors most often associated with dopaminergic treatment. Presently, there is a lack of high quality evidence available to guide their management. This manuscript reviews current management strategies, before concentrating on the concept of dopamine agonist withdrawal syndrome and its implications for the management of impulse control disorders. Further, we focus on controversies including the role of more recently available anti-parkinsonian drugs, and potential future approaches involving routes of drug delivery, non-pharmacological treatments (such as cognitive behaviour therapy and deep brain stimulation), and other as yet experimental strategies. PMID:25607799

Multilevel Mechanisms of Implementation Strategies in Mental Health: Integrating Theory, Research, and Practice

PubMed Central

2015-01-01

A step toward the development of optimally effective, efficient, and feasible implementation strategies that increase evidence-based treatment integration in mental health services involves identification of the multilevel mechanisms through which these strategies influence implementation outcomes. This article (a) provides an orientation to, and rationale for, consideration of multilevel mediating mechanisms in implementation trials, and (b) systematically reviews randomized controlled trials that examined mediators of implementation strategies in mental health. Nine trials were located. Mediation-related methodological deficiencies were prevalent and no trials supported a hypothesized mediator. The most common reason was failure to engage the mediation target. Discussion focuses on directions to accelerate implementation strategy development in mental health. PMID:26474761

Neurorehabilitation strategies for poststroke oropharyngeal dysphagia: from compensation to the recovery of swallowing function.

PubMed

Cabib, Christopher; Ortega, Omar; Kumru, Hatice; Palomeras, Ernest; Vilardell, Natalia; Alvarez-Berdugo, Daniel; Muriana, Desirée; Rofes, Laia; Terré, Rosa; Mearin, Fermín; Clavé, Pere

2016-09-01

Oropharyngeal dysphagia (OD) is very prevalent among poststroke patients, causing severe complications but lacking specific neurorehabilitation treatment. This review covers advances in the pathophysiology, diagnosis, and physiologically based neurorehabilitation strategies for poststroke OD. The pathophysiology of oropharyngeal biomechanics can be assessed by videofluoroscopy, as delayed laryngeal vestibule closure is closely associated with aspiration. Stroke may affect afferent or efferent neuronal circuits participating in deglutition. The integrity of oropharyngeal-cortical afferent pathways can be assessed by electroencephalography through sensory-evoked potentials by pharyngeal electrical stimulation, while corticopharyngeal efferent pathways can be characterized by electromyography through motor-evoked potentials by transcranial magnetic stimulation. Dysfunction in both cortico-mediated evoked responses is associated with delayed swallow response and aspiration. Studies have reported hemispherical asymmetry on motor control of swallowing and the relevance of impaired oropharyngeal sensitivity on aspiration. Advances in treatment include improvements in compensatory strategies but are mainly focused on (1) peripheral stimulation strategies and (2) central, noninvasive stimulation strategies with evidence of their clinical benefits. Characterization of poststroke OD is evolving from the assessment of impaired biomechanics to the sensorimotor integration processes involved in deglutition. Treatment is also changing from compensatory strategies to promoting brain plasticity, both to recover swallow function and to improve brain-related swallowing dysfunction. © 2016 New York Academy of Sciences.

[X-ray semiotics of sialolithiasis in functional digital subtraction sialography].

PubMed

Iudin, L A; Kondrashin, S A; Afanas'ev, V V; Shchipskiĭ, A V

1995-01-01

Twenty-seven patients with sialolithiasis were examined using functional subtraction sialography developed by the authors. Differential diagnostic signs characterizing the degree of involvement of the salivary gland were defined. High efficacy of the method helps correctly plan the treatment strategy.

What is a “good” treatment decision?: Decisional control, knowledge, treatment decision-making, and quality of life in men with clinically localized prostate cancer

PubMed Central

Orom, Heather; Biddle, Caitlin; Underwood, Willie; Nelson, Christian J.; Homish, D. Lynn

2016-01-01

Objective We explored whether active patient involvement in decision making and greater patient knowledge are associated with better treatment decision making experiences and better quality of life (QOL) among men with clinically localized prostate cancer. Localized prostate cancer treatment decision-making is an advantageous model for studying patient treatment decision-making dynamics as there are multiple treatment options and a lack of empirical evidence to recommend one over the other; consequently, it is recommended that patients be fully involved in making the decision. Methods Men with newly diagnosed clinically localized prostate cancer (N=1529) completed measures of decisional control, prostate cancer knowledge, and their decision-making experience (decisional conflict, and decision-making satisfaction and difficulty) shortly after they made their treatment decision. Prostate cancer-specific QOL was assessed 6-months after treatment. Results More active involvement in decision making and greater knowledge were associated with lower decisional conflict and higher decision-making satisfaction, but greater decision-making difficulty. An interaction between decisional control and knowledge revealed that greater knowledge was only associated with greater difficulty for men actively involved in making the decision (67% of sample). Greater knowledge, but not decisional control predicted better QOL 6-months post-treatment. Conclusion Although men who are actively involved in decision making and more knowledgeable may make more informed decisions, they could benefit from decisional support (e.g., decision-making aids, emotional support from providers, strategies for reducing emotional distress) to make the process easier. Men who were more knowledgeable about prostate cancer and treatment side effects at the time they made their treatment decision may have appraised their QOL as higher because they had realistic expectations about side effects. PMID:26957566

What Is a "Good" Treatment Decision? Decisional Control, Knowledge, Treatment Decision Making, and Quality of Life in Men with Clinically Localized Prostate Cancer.

PubMed

Orom, Heather; Biddle, Caitlin; Underwood, Willie; Nelson, Christian J; Homish, D Lynn

2016-08-01

We explored whether active patient involvement in decision making and greater patient knowledge are associated with better treatment decision-making experiences and better quality of life (QOL) among men with clinically localized prostate cancer. Localized prostate cancer treatment decision making is an advantageous model for studying patient treatment decision-making dynamics because there are multiple treatment options and a lack of empirical evidence to recommend one over the other; consequently, it is recommended that patients be fully involved in making the decision. Men with newly diagnosed clinically localized prostate cancer (N = 1529) completed measures of decisional control, prostate cancer knowledge, and decision-making experiences (decisional conflict and decision-making satisfaction and difficulty) shortly after they made their treatment decision. Prostate cancer-specific QOL was assessed at 6 months after treatment. More active involvement in decision making and greater knowledge were associated with lower decisional conflict and higher decision-making satisfaction but greater decision-making difficulty. An interaction between decisional control and knowledge revealed that greater knowledge was only associated with greater difficulty for men actively involved in making the decision (67% of sample). Greater knowledge, but not decisional control, predicted better QOL 6 months after treatment. Although men who are actively involved in decision making and more knowledgeable may make more informed decisions, they could benefit from decisional support (e.g., decision-making aids, emotional support from providers, strategies for reducing emotional distress) to make the process easier. Men who were more knowledgeable about prostate cancer and treatment side effects at the time that they made their treatment decision may have appraised their QOL as higher because they had realistic expectations about side effects. © The Author(s) 2016.

Craniopharyngioma and hypothalamic injury: latest insights into consequent eating disorders and obesity

PubMed Central

Müller, Hermann L.

2016-01-01

Purpose of review Hypothalamic alterations, pathological or treatment induced, have major impact on prognosis in craniopharyngioma patients mainly because of consequent hypothalamic obesity. Recent insight in molecular genetics, treatment strategies, risk factors and outcomes associated with hypothalamic obesity provide novel therapeutic perspectives. This review includes relevant publications since 2013. Recent findings Recent findings confirm that alterations in posterior hypothalamic areas because of tumour location and/or treatment-related injuries are associated with severe hypothalamic obesity, reduced overall survival and impaired quality of life in long-term survivors of childhood-onset craniopharyngioma. However, eating disorders are observed because of hypothalamic obesity without clear disease-specific patterns. Treatment options for hypothalamic obesity are very limited. Treatment with invasive, nonreversible bariatric methods such as Roux-en-Y gastric bypass is most efficient in weight reduction, but controversial in the paediatric population because of medical, ethical, and legal considerations. Accordingly, treatment in craniopharyngioma should focus on prevention of (further) hypothalamic injury. Presurgical imaging for grading of hypothalamic involvement should be the basis for hypothalamus-sparing strategies conducted by experienced multidisciplinary teams. Summary Until a nonsurgical therapeutic option for hypothalamic obesity for paediatric patients is found, prevention of hypothalamic injury should be the preferred treatment strategy, conducted exclusively by experienced multidisciplinary teams. PMID:26574645

The surgical treatment of short stature: management strategy and local experience.

PubMed

Koczewski, Paweł; Shadi, Milud; Napiontek, Marek

2002-08-30

Background. This article presents the indications and counterindications for the application of limb lengthening using distraction osteogenesis in the treatment of patients with short stature. Various treatment strategies are described. The factors influencing the choice of strategy are discussed, the means used to determine the extent and level of lengthening, and the optimum age to begin treatment. Material and methods. On the basis of their own material the authors present the problems, obstacles, and complications occurring during treatment. During the period 1997-2000 a total of 5 patients were treated for short stature, averaging 18 years of age. In these cases the "crossed" technique of surgical treatment was applied, using an Ilizarov apparatus on the tibia and an Italian modification on the leg. Results. A total of 8 tibial segments (ave. 7 cm) and 8 femoral segments (ave. 7.5 cm) were lengthened. The average increase in stature was 14.8 cm (a 12% increase over the growth prior to treatment). Conclusions. The methods applied produced good results in patients with non-proportional dwarfism, while the majority of complications involved patients with constitutionally short stature. This confirms the necessity to make a strict selection of healthy persons undertaking to increase their stature for cosmetic reasons.

Treatment of PANDAS and PANS: a systematic review.

PubMed

Sigra, Sofia; Hesselmark, Eva; Bejerot, Susanne

2018-03-01

Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) are a subtype of acute-onset obsessive-compulsive disorder (OCD) thought to be caused by an autoimmune response to group A streptococcal infection. Based on this proposed pathophysiology, alternative treatments for acute-onset OCD have been introduced, including antibiotics and immunomodulatory interventions. However, the literature on treatment of PANDAS is diverse, and clinical consensus regarding optimal treatment strategy is lacking. We conducted a systematic review of articles in PubMed, Cochrane Library, and Scopus that addressed treatment for PANDAS and related disorders. Twelve research studies involving the following treatments met inclusion criteria: penicillin, azithromycin, intravenous immunoglobulin, plasma exchange, tonsillectomy, cognitive behavior therapy, NSAID and corticosteroids. In addition, 65 case reports in which patients received immunomodulatory treatments, antibiotics, and/or psychotropics were identified. We determined that rigorously conducted research regarding treatments for PANDAS is scarce, and published studies have a high risk of bias. Further research is needed in which promising treatment strategies for PANDAS and other variants of OCD with proposed autoimmune etiology are rigorously investigated. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Potential approaches for heterologous prion protein treatment of prion diseases

PubMed Central

Seelig, Davis M.; Goodman, Patricia A.; Skinner, Pamela J.

2016-01-01

ABSTRACT Prion diseases, or transmissible spongiform encephalopathies (TSEs) are progressive, fatal neurodegenerative diseases with no effective treatment. The pathology of these diseases involves the conversion of a protease sensitive form of the cellular prion protein (PrPC) into a protease resistant infectious form (PrPres). The efficiency of this conversion is predicated upon a number of factors, most notably a strong homology between cellular PrPC and PrPres. In our recently published study, we infected mice with the RML-Chandler strain of scrapie and treated them with heterologous hamster prion proteins. This treatment was seen to reduce clinical signs of prion disease, to delay the onset of clinical symptoms and to prolong survival. In this current article we discuss potential mechanisms of action of treatment with heterologous prion proteins. We also discuss potential extensions of these studies using a heterologous rabbit PrP-based treatment strategy or a peptide based strategy, and improvement of treatment delivery including a lentiviral-based system. PMID:26636482

Integrating substance abuse treatment and criminal justice supervision.

PubMed

Marlowe, Douglas B

2003-08-01

Proponents of a pure public safety perspective on the drug problem hold that drug-involved offenders require consistent and intensive supervision by criminal justice authorities in order to stay off drugs and out of trouble. In contrast, proponents of a thoroughgoing public health perspective commonly argue that clients perform better if they are left alone to develop an effective therapeutic alliance with counselors. Both may be correct, but with respect to different groups of offenders. One approach has shown consistent promise for reducing drug use and criminal recidivism: an integrated public health-public safety strategy that combines community-based drug abuse treatment with ongoing criminal justice supervision. This article presents promising findings from programs implementing this strategy and discusses best treatment practices to meet the needs of both low-risk and high-risk clients.

Identifying and ranking implicit leadership strategies to promote evidence-based practice implementation in addiction health services.

PubMed

Guerrero, Erick G; Padwa, Howard; Fenwick, Karissa; Harris, Lesley M; Aarons, Gregory A

2016-05-14

Despite a solid research base supporting evidence-based practices (EBPs) for addiction treatment such as contingency management and medication-assisted treatment, these services are rarely implemented and delivered in community-based addiction treatment programs in the USA. As a result, many clients do not benefit from the most current and efficacious treatments, resulting in reduced quality of care and compromised treatment outcomes. Previous research indicates that addiction program leaders play a key role in supporting EBP adoption and use. The present study expanded on this previous work to identify strategies that addiction treatment program leaders report using to implement new practices. We relied on a staged and iterative mixed-methods approach to achieve the following four goals: (a) collect data using focus groups and semistructured interviews and conduct analyses to identify implicit managerial strategies for implementation, (b) use surveys to quantitatively rank strategy effectiveness, (c) determine how strategies fit with existing theories of organizational management and change, and (d) use a consensus group to corroborate and expand on the results of the previous three stages. Each goal corresponded to a methodological phase, which included data collection and analytic approaches to identify and evaluate leadership interventions that facilitate EBP implementation in community-based addiction treatment programs. Findings show that the top-ranked strategies involved the recruitment and selection of staff members receptive to change, offering support and requesting feedback during the implementation process, and offering in vivo and hands-on training. Most strategies corresponded to emergent implementation leadership approaches that also utilize principles of transformational and transactional leadership styles. Leadership behaviors represented orientations such as being proactive to respond to implementation needs, supportive to assist staff members during the uptake of new practices, knowledgeable to properly guide the implementation process, and perseverant to address ongoing barriers that are likely to stall implementation efforts. These findings emphasize how leadership approaches are leveraged to facilitate the implementation and delivery of EBPs in publicly funded addiction treatment programs. Findings have implications for the content and structure of leadership interventions needed in community-based addiction treatment programs and the development of leadership interventions in these and other service settings.

Completion of Gamma Knife radiosurgery for AVM treatment after unplanned interruption-technical note.

PubMed

Raman, Hari S; Santanam, Lakshmi; Vellimana, Ananth K; Drzymala, Robert E; Tsien, Christina I; Zipfel, Gregory J

2018-02-17

Gamma Knife radiosurgery is an established technique for non-urgent treatment of various intracranial pathologies. Intra-procedural dislodgement of the stereotactic frame is an uncommon occurrence that could lead to abortion of ongoing treatment and necessitate more invasive treatment strategies. In this case report, we describe a novel method for resumption of Gamma Knife treatment after an unplanned intra-procedural interruption. The case example involves a radiosurgical treatment of a Spetzler-Martin grade I arteriovenous malformation. Our technique involves integration of scans and coordinate systems from two imaging sessions using the composite isodose line to resolve translational differences, thereby limiting delivery of remaining shots to the untreated region of the lesion. MRI follow-up at 13 months showed a reduction in the nidus size with no evidence of any radiation injury to the surrounding brain parenchyma. We believe this technique will allow care teams to effectively salvage interrupted Gamma Knife procedures and reduce progression to more invasive treatment options.

Increasing Neuroplasticity to Bolster Chronic Pain Treatment: A Role for Intermittent Fasting and Glucose Administration?

PubMed Central

Sibille, KT; Bartsch, F; Reddy, D; Fillingim, RB; Keil, A

2016-01-01

Neuroplastic changes in brain structure and function are not only a consequence of chronic pain but are involved in the maintenance of pain symptoms. Thus, promoting adaptive, treatment responsive neuroplasticity represents a promising clinical target. Emerging evidence about the human brain’s response to an array of behavioral and environmental interventions may assist in identifying targets to facilitate increased neurobiological receptivity, promoting healthy neuroplastic changes. Specifically, strategies to maximize neuroplastic responsiveness to chronic pain treatment could enhance treatment gains by optimizing learning and positive central nervous system (CNS) adaptation. Periods of heightened plasticity have been traditionally identified with the early years of development. More recent research however has identified a wide spectrum of methods that can be used to “re-open” and enhance plasticity and learning in adults. In addition to transcranial direct current stimulation and transcranial magnetic stimulation, behavioral and pharmacological interventions have been investigated. Intermittent fasting and glucose administration are two propitious strategies, which are non-invasive, inexpensive to administer, implementable in numerous settings, and may be applicable across differing chronic pain treatments. Key findings and neurophysiological mechanisms are summarized, providing evidence for the potential clinical contributions of these two strategies toward ameliorating chronic pain. PMID:26848123

Theory-based training strategies for modifying practitioner concerns about exposure therapy.

PubMed

Farrell, Nicholas R; Deacon, Brett J; Dixon, Laura J; Lickel, James J

2013-12-01

Despite the well-established efficacy of exposure therapy in the treatment of pathological anxiety, many therapists believe this treatment carries an unacceptably high risk for harm, is intolerable for patients, and poses a number of ethical quandaries. These beliefs have been shown to account for two related problems: (a) underutilization of exposure therapy, and (b) overly cautious and suboptimal delivery the treatment, which likely attenuates treatment outcomes. At present, there is little guidance for those who train exposure therapists to address these concerns. This article reviews therapist negative beliefs about exposure therapy and discusses their modification based on findings from social and cognitive psychology pertinent to belief change, including dual-processing in reasoning, the need for cognition and affect, and attitude inoculation. A number of strategies are offered for augmenting training in exposure therapy in order to promote positive beliefs about the treatment. These strategies involve: (a) therapists engaging in simulated exposure therapy exercises and presenting arguments in defense of exposure's safety, tolerability, and ethicality, and (b) training therapists using emotion-based appeals (e.g., case examples) to supplement research findings. Directions for future research on practitioner concerns about exposure therapy are discussed. Copyright © 2013 Elsevier Ltd. All rights reserved.

Aggression and Agitation in Dementia.

PubMed

Wolf, M Uri; Goldberg, Yael; Freedman, Morris

2018-06-01

This article reviews the treatment of aggression and agitation in dementia. Both nonpharmacologic and pharmacologic approaches to responsive behaviors are discussed. Practical treatment strategies are applied to common behavioral symptoms. Aggressive and agitated behavior is common in dementia. Behavioral symptoms lead to reduced quality of life and distress for both patients and caregivers. They can also lead to poor outcomes and are associated with significant financial implications for the individual and health care system. A wide range of difficult behaviors exists, with limited evidence for deciding on treatment. Clinicians should integrate the available evidence with practical and commonsense strategies to target these difficult-to-treat behaviors. Treating aggression and agitation in dementia is challenging. Viewing behaviors as a response to either internal or external stimuli can help guide treatment. Treatment should emphasize nonpharmacologic approaches as an initial step, using practical and commonsense strategies. Caregivers and family should be actively involved in the planning and implementation of behavioral plans. It is essential to minimize both medical and nonmedical factors that may be contributing to behaviors. When pharmacologic options are required, it is important to choose medications that will target specific behavioral goals, having both practical consideration and the best evidence in mind.

MicroRNA and receptor mediated signaling pathways as potential therapeutic targets in heart failure.

PubMed

Tuttolomondo, Antonino; Simonetta, Irene; Pinto, Antonio

2016-11-01

Cardiac remodelling is a complex pathogenetic pathway involving genome expression, molecular, cellular, and interstitial changes that cause changes in size, shape and function of the heart after cardiac injury. Areas covered: We will review recent advances in understanding the role of several receptor-mediated signaling pathways and micro-RNAs, in addition to their potential as candidate target pathways in the pathogenesis of heart failure. The myocyte is the main target cell involved in the remodelling process via ischemia, cell necrosis and apoptosis (by means of various receptor pathways), and other mechanisms mediated by micro-RNAs. We will analyze the role of some receptor mediated signaling pathways such as natriuretic peptides, mediators of glycogen synthase kinase 3 and ERK1/2 pathways, beta-adrenergic receptor subtypes and relaxin receptor signaling mechanisms, TNF/TNF receptor family and TWEAK/Fn14 axis, and some micro-RNAs as candidate target pathways in pathogenesis of heart failure. These mediators of receptor-mediated pathways and micro-RNA are the most addressed targets of emerging therapies in modern heart failure treatment strategies. Expert opinion: Future treatment strategies should address mediators involved in multiple steps within heart failure pathogenetic pathways.

Does metacognitive strategy instruction improve impaired receptive cognitive-communication skills following acquired brain injury?

PubMed

Copley, Anna; Smith, Kathleen; Savill, Katelyn; Finch, Emma

2015-01-01

To investigate if metacognitive strategy instruction (MSI) improves the receptive language skills of adults with cognitive-communication disorders secondary to acquired brain injury (ABI). An ABA intervention programme was implemented with eight adults with ABI, aged 25-70 years. The Measure of Cognitive-Linguistic Abilities (MCLA) was administered at baseline and following treatment. The treatment employed in this study involved three components: individual goal-based therapy, group remediation therapy using self-instruction and home practice. No receptive language sub-tests of the MCLA reached statistical significance. However, participants' raw score improvements in receptive language sub-tests indicated that MSI may be effective at remediating CCDs following ABI. Preliminary findings indicate that MSI may be effective in improving receptive language skills in adults with CCDs following ABI. Further research involving a more rigorous study, a larger sample size and a more reliable outcome measure is necessary and may provide statistically significant evidence for the effectiveness of MSI for remediating receptive language disorders.

[Progressive renal insufficiency in a 55-year-old man with psoriasis].

PubMed

Herfurth, K; Busch, M; Gröne, H J; Wolf, G

2018-06-05

Treatment with tumor necrosis factor alpha (TNF-α) inhibitors is a well-established therapeutic strategy for various autoimmune diseases. However, little is known about renal complications and possible causality of renal injury due to this treatment. The following case of a patient with psoriasis demonstrates the difficulties in classifying renal complications of anti-TNF-α therapy versus kidney involvement caused by the underlying disease.

Biomarkers of anhedonic-like behavior, antidepressant drug refraction, and stress resilience in a rat model of depression.

PubMed

Christensen, T; Bisgaard, C F; Wiborg, O

2011-11-24

The aim of the present study was to identify potential biomarkers for depression in the search for novel disease targets and treatment regimens. Furthermore, the study includes a search for biomarkers involved in treatment resistance and stress resilience in order to investigate mechanisms underlying antidepressant drug refraction and stress-coping strategies. Depression-related transcriptomic changes in gene expression profiles were investigated in laser-captured microdissected (LCM) rat hippocampal granular cell layers (GCL) using the chronic mild stress (CMS) rat model of depression and chronic administration of two selective serotonin reuptake inhibitors (SSRIs), escitalopram and sertraline. CMS rats were segregated into diverging groups according to behavioral readouts, and under stringent constraints, the associated differential gene regulations were analyzed. Accordingly, we identified four genes associated with recovery, two genes implicated in treatment resistance, and three genes involved in stress resilience. The identified genes associated with mechanisms of cellular plasticity, including signal transduction, cell proliferation, cell differentiation, and synaptic release. Hierarchical clustering analysis confirmed the subgroup segregation pattern in the CMS model. Thus antidepressant treatment refractors cluster with anhedonic-like rats, and, interestingly, stress-resilient rats cluster with rats undergoing antidepressant-mediated recovery from anhedonia, suggesting antidepressant mechanisms of action to emulate endogenous stress-coping strategies. Copyright © 2011 IBRO. Published by Elsevier Ltd. All rights reserved.

Contingency Space Analysis: An Alternative Method for Identifying Contingent Relations from Observational Data

PubMed Central

Martens, Brian K; DiGennaro, Florence D; Reed, Derek D; Szczech, Frances M; Rosenthal, Blair D

2008-01-01

Descriptive assessment methods have been used in applied settings to identify consequences for problem behavior, thereby aiding in the design of effective treatment programs. Consensus has not been reached, however, regarding the types of data or analytic strategies that are most useful for describing behavior–consequence relations. One promising approach involves the analysis of conditional probabilities from sequential recordings of behavior and events that follow its occurrence. In this paper we review several strategies for identifying contingent relations from conditional probabilities, and propose an alternative strategy known as a contingency space analysis (CSA). Step-by-step procedures for conducting and interpreting a CSA using sample data are presented, followed by discussion of the potential use of a CSA for conducting descriptive assessments, informing intervention design, and evaluating changes in reinforcement contingencies following treatment. PMID:18468280

Increasing Neuroplasticity to Bolster Chronic Pain Treatment: A Role for Intermittent Fasting and Glucose Administration?

PubMed

Sibille, Kimberly T; Bartsch, Felix; Reddy, Divya; Fillingim, Roger B; Keil, Andreas

2016-03-01

Neuroplastic changes in brain structure and function are not only a consequence of chronic pain but are involved in the maintenance of pain symptoms. Thus, promotion of adaptive, treatment-responsive neuroplasticity represents a promising clinical target. Emerging evidence about the human brain's response to an array of behavioral and environmental interventions may assist in identifying targets to facilitate increased neurobiological receptivity, promoting healthy neuroplastic changes. Specifically, strategies to maximize neuroplastic responsiveness to chronic pain treatment could enhance treatment gains by optimization of learning and positive central nervous system adaptation. Periods of heightened plasticity have been traditionally identified with the early years of development. More recent research, however, has identified a wide spectrum of methods that can be used to "reopen" and enhance plasticity and learning in adults. In addition to transcranial direct current stimulation and transcranial magnetic stimulation, behavioral and pharmacological interventions have been investigated. Intermittent fasting and glucose administration are two propitious strategies, that are noninvasive, inexpensive to administer, implementable in numerous settings, and might be applicable across differing chronic pain treatments. Key findings and neurophysiological mechanisms are summarized, and evidence for the potential clinical contributions of these two strategies toward ameliorating chronic pain is presented. Neuroplastic changes are a defining feature of chronic pain and a complicating factor in treatment. Noninvasive strategies to optimize the brain's response to treatment interventions might improve learning and memory, increase the positive adaptability of the central nervous system, and enhance treatment outcomes. Copyright © 2016 American Pain Society. Published by Elsevier Inc. All rights reserved.

Air quality impacts of transit improvement, preferential lane, and carpool programs: an annotated bibliography of demonstration and analytical experience. Final report

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

DiRenzo, J.F.; Rubin, R.B.

1978-03-01

In accordance with the Clean Air Act Amendments of 1977, the Environmental Protection Agency is evaluating the use and cost-effectiveness of alternative short-range transit fare and service improvement strategies, carpool and vanpool strategies, and strategies involving the preferential treatment of high occupancy vehicles to improve air quality in urban areas. The evaluation of individual strategies and combinations of the above strategies includes their emission and air quality impacts and their related energy, noise, and economic impacts. A comprehensive literature review was also conducted, as part of this evaluation, to identify both observed and projected travel, emission, air quality, energy, noise,more » and economic impacts of the short-range low-cost strategies of interest.« less

The Cost Effectiveness of Pandemic Influenza Interventions: A Pandemic Severity Based Analysis

PubMed Central

Milne, George J.; Halder, Nilimesh; Kelso, Joel K.

2013-01-01

Background The impact of a newly emerged influenza pandemic will depend on its transmissibility and severity. Understanding how these pandemic features impact on the effectiveness and cost effectiveness of alternative intervention strategies is important for pandemic planning. Methods A cost effectiveness analysis of a comprehensive range of social distancing and antiviral drug strategies intended to mitigate a future pandemic was conducted using a simulation model of a community of ∼30,000 in Australia. Six pandemic severity categories were defined based on case fatality ratio (CFR), using data from the 2009/2010 pandemic to relate hospitalisation rates to CFR. Results Intervention strategies combining school closure with antiviral treatment and prophylaxis are the most cost effective strategies in terms of cost per life year saved (LYS) for all severity categories. The cost component in the cost per LYS ratio varies depending on pandemic severity: for a severe pandemic (CFR of 2.5%) the cost is ∼$9 k per LYS; for a low severity pandemic (CFR of 0.1%) this strategy costs ∼$58 k per LYS; for a pandemic with very low severity similar to the 2009 pandemic (CFR of 0.03%) the cost is ∼$155 per LYS. With high severity pandemics (CFR >0.75%) the most effective attack rate reduction strategies are also the most cost effective. During low severity pandemics costs are dominated by productivity losses due to illness and social distancing interventions, while for high severity pandemics costs are dominated by hospitalisation costs and productivity losses due to death. Conclusions The most cost effective strategies for mitigating an influenza pandemic involve combining sustained social distancing with the use of antiviral agents. For low severity pandemics the most cost effective strategies involve antiviral treatment, prophylaxis and short durations of school closure; while these are cost effective they are less effective than other strategies in reducing the infection rate. PMID:23585906

A Brief Overview of Tauopathy: Causes, Consequences, and Therapeutic Strategies.

PubMed

Orr, Miranda E; Sullivan, A Campbell; Frost, Bess

2017-07-01

There are currently no disease-modifying therapies for the treatment of tauopathies, a group of progressive neurodegenerative disorders that are pathologically defined by the presence of tau protein aggregates in the brain. Current challenges for the treatment of tauopathies include the inability to diagnose early and to confidently discriminate between distinct tauopathies in patients, alongside an incomplete understanding of the cellular mechanisms involved in pathogenic tau-induced neuronal death and dysfunction. In this review, we describe current diagnostic and therapeutic strategies, known drivers of pathogenic tau formation, recent contributions to our current mechanistic understanding of how pathogenic tau induces neuronal death, and potential diagnostic and therapeutic approaches. Copyright © 2017 Elsevier Ltd. All rights reserved.

Stereotactic Radiosurgery and Hypofractionated Radiotherapy for Glioblastoma.

PubMed

Shah, Jennifer L; Li, Gordon; Shaffer, Jenny L; Azoulay, Melissa I; Gibbs, Iris C; Nagpal, Seema; Soltys, Scott G

2018-01-01

Glioblastoma is the most common primary brain tumor in adults. Standard therapy depends on patient age and performance status but principally involves surgical resection followed by a 6-wk course of radiation therapy given concurrently with temozolomide chemotherapy. Despite such treatment, prognosis remains poor, with a median survival of 16 mo. Challenges in achieving local control, maintaining quality of life, and limiting toxicity plague treatment strategies for this disease. Radiotherapy dose intensification through hypofractionation and stereotactic radiosurgery is a promising strategy that has been explored to meet these challenges. We review the use of hypofractionated radiotherapy and stereotactic radiosurgery for patients with newly diagnosed and recurrent glioblastoma. Copyright © 2017 by the Congress of Neurological Surgeons.

Novel delivery approaches for cancer therapeutics.

PubMed

Mitra, Ashim K; Agrahari, Vibhuti; Mandal, Abhirup; Cholkar, Kishore; Natarajan, Chandramouli; Shah, Sujay; Joseph, Mary; Trinh, Hoang M; Vaishya, Ravi; Yang, Xiaoyan; Hao, Yi; Khurana, Varun; Pal, Dhananjay

2015-12-10

Currently, a majority of cancer treatment strategies are based on the removal of tumor mass mainly by surgery. Chemical and physical treatments such as chemo- and radiotherapies have also made a major contribution in inhibiting rapid growth of malignant cells. Furthermore, these approaches are often combined to enhance therapeutic indices. It is widely known that surgery, chemo- and radiotherapy also inhibit normal cells growth. In addition, these treatment modalities are associated with severe side effects and high toxicity which in turn lead to low quality of life. This review encompasses novel strategies for more effective chemotherapeutic delivery aiming to generate better prognosis. Currently, cancer treatment is a highly dynamic field and significant advances are being made in the development of novel cancer treatment strategies. In contrast to conventional cancer therapeutics, novel approaches such as ligand or receptor based targeting, triggered release, intracellular drug targeting, gene delivery, cancer stem cell therapy, magnetic drug targeting and ultrasound-mediated drug delivery, have added new modalities for cancer treatment. These approaches have led to selective detection of malignant cells leading to their eradication with minimal side effects. Lowering multi-drug resistance and involving influx transportation in targeted drug delivery to cancer cells can also contribute significantly in the therapeutic interventions in cancer. Copyright © 2015 Elsevier B.V. All rights reserved.

Chronic Fatigue Syndrome and Women: Can Therapy Help?

ERIC Educational Resources Information Center

Burke, Susan G.

1992-01-01

Presents current research on chronic fatigue syndrome, which currently afflicts mostly females between ages of 25 and 55. Notes that, because depression is common symptom of chronic fatigue syndrome, mental health practitioners are often involved with victims and must formulate appropriate treatment strategy that considers physiological,…

Treating alcoholism as a chronic disease: approaches to long-term continuing care.

PubMed

McKay, James R; Hiller-Sturmhofel, Susanne

2011-01-01

For many patients, alcohol and other drug (AOD) use disorders are chronic, recurring conditions involving multiple cycles of treatment, abstinence, and relapse. To disrupt this cycle, treatment can include continuing care to reduce the risk of relapse. The most commonly used treatment approach is initial intensive inpatient or outpatient care based on 12-step principles, followed by continuing care involving self-help groups, 12-step group counseling, or individual therapy. Although these programs can be effective, many patients drop out of initial treatment or do not complete continuing care. Thus, researchers and clinicians have begun to develop alternative approaches to enhance treatment retention in both initial and continuing care. One focus of these efforts has been the design of extended treatment models. These approaches increasingly blur the distinction between initial and continuing care and aim to prolong treatment participation by providing a continuum of care. Other researchers have focused on developing alternative treatment strategies (e.g., telephone-based interventions) that go beyond traditional settings and adaptive treatment algorithms that may improve outcomes for clients who do not respond well to traditional approaches.

Molecular mechanisms of action of quercetin in cancer: recent advances.

PubMed

Kashyap, Dharambir; Mittal, Sonam; Sak, Katrin; Singhal, Paavan; Tuli, Hardeep Singh

2016-10-01

In the last few decades, the scientific community has discovered an immense potential of natural compounds in the treatment of dreadful diseases such as cancer. Besides the availability of a variety of natural bioactive molecules, efficacious cancer therapy still needs to be developed. So, to design an efficacious cancer treatment strategy, it is essential to understand the interactions of natural molecules with their respective cellular targets. Quercetin (Quer) is a naturally occurring flavonol present in many commonly consumed food items. It governs numerous intracellular targets, including the proteins involved in apoptosis, cell cycle, detoxification, antioxidant replication, and angiogenesis. The weight of available synergistic studies vigorously fortifies the utilization of Quer as a chemoprevention drug. This extensive review covers various therapeutic interactions of Quer with their recognized cellular targets involved in cancer treatment.

Increases in Drug and Opioid-Involved Overdose Deaths - United States, 2010-2015.

PubMed

Rudd, Rose A; Seth, Puja; David, Felicita; Scholl, Lawrence

2016-12-30

The U.S. opioid epidemic is continuing, and drug overdose deaths nearly tripled during 1999-2014. Among 47,055 drug overdose deaths that occurred in 2014 in the United States, 28,647 (60.9%) involved an opioid (1). Illicit opioids are contributing to the increase in opioid overdose deaths (2,3). In an effort to target prevention strategies to address the rapidly changing epidemic, CDC examined overall drug overdose death rates during 2010-2015 and opioid overdose death rates during 2014-2015 by subcategories (natural/semisynthetic opioids, methadone, heroin, and synthetic opioids other than methadone).* Rates were stratified by demographics, region, and by 28 states with high quality reporting on death certificates of specific drugs involved in overdose deaths. During 2015, drug overdoses accounted for 52,404 U.S. deaths, including 33,091 (63.1%) that involved an opioid. There has been progress in preventing methadone deaths, and death rates declined by 9.1%. However, rates of deaths involving other opioids, specifically heroin and synthetic opioids other than methadone (likely driven primarily by illicitly manufactured fentanyl) (2,3), increased sharply overall and across many states. A multifaceted, collaborative public health and law enforcement approach is urgently needed. Response efforts include implementing the CDC Guideline for Prescribing Opioids for Chronic Pain (4), improving access to and use of prescription drug monitoring programs, enhancing naloxone distribution and other harm reduction approaches, increasing opioid use disorder treatment capacity, improving linkage into treatment, and supporting law enforcement strategies to reduce the illicit opioid supply.

The synergistic effects of traditional Chinese herbs and radiotherapy for cancer treatment

PubMed Central

JIA, LILI; MA, SHUMEI; HOU, XUE; WANG, XIN; QASED, ABU BAKER LAYTH; SUN, XUEFEI; LIANG, NAN; LI, HUICHENG; YI, HEQING; KONG, DEJUAN; LIU, XIAODONG; FAN, FEIYUE

2013-01-01

Traditional Chinese medicine (TCM) has been demonstrated to have potent cytotoxic activity against certain malignant tumors. Ionizing radiation (IR) is one of the most effective methods used in the clinical treatment of cancer. The drawback of a single formula is that it limits the treatment efficacy for cancer, while comprehensive strategies require additional theoretical support. However, a combination of different antitumor treatment modalities is advantageous in restricting the non-specific toxicity often observed with an extremely high dose of a single regimen. The induction of apoptotic cell death is a significant process in tumor cells following radiotherapy or chemotherapy, and resistance to these treatments has been linked to a low propensity for apoptosis. Autophagy is a response of cancer cells to IR or chemotherapy, and involves the prominent formation of autophagic vacuoles in the cytoplasm. In this review, the synergistic effects of TCM and radiotherapy are summarized and the underlying mechanisms are illustrated, providing new therapeutic strategies for cancer. PMID:23760551

Service user and caregiver involvement in mental health system strengthening in low- and middle-income countries: a cross-country qualitative study.

PubMed

Lempp, H; Abayneh, S; Gurung, D; Kola, L; Abdulmalik, J; Evans-Lacko, S; Semrau, M; Alem, A; Thornicroft, G; Hanlon, C

2018-02-01

The aims of this paper are to: (i) explore the experiences of involvement of mental health service users, their caregivers, mental health centre heads and policy makers in mental health system strengthening in three low- and middle-income countries (LMICs) (Ethiopia, Nepal and Nigeria); (ii) analyse the potential benefits and barriers of such involvement; and (iii) identify strategies required to achieve greater service user and caregiver participation. A cross-country qualitative study was conducted, interviewing 83 stakeholders of mental health services. Our analysis showed that service user and caregiver involvement in the health system strengthening process was an alien concept for most participants. They reported very limited access to direct participation. Stigma and poverty were described as the main barriers for involvement. Several strategies were identified by participants to overcome existing hurdles to facilitate service user and caregiver involvement in the mental health system strengthening process, such as support to access treatment, mental health promotion and empowerment of service users. This study suggests that capacity building for service users, and strengthening of user groups would equip them to contribute meaningfully to policy development from informed perspectives. Involvement of service users and their caregivers in mental health decision-making is still in its infancy in LMICs. Effective strategies are required to overcome existing barriers, for example making funding more widely available for Ph.D. studies in participatory research with service users and caregivers to develop, implement and evaluate approaches to involvement that are locally and culturally acceptable in LMICs.

A Systematic Review of Relaxation, Meditation, and Guided Imagery Strategies for Symptom Management in Heart Failure

PubMed Central

Kwekkeboom, Kristine L.; Bratzke, Lisa C.

2015-01-01

Background Pain, dyspnea, fatigue, and sleep disturbance are prevalent and distressing symptoms in persons with advanced heart failure. Although many lifestyle and self-care interventions have been developed to control heart failure progression, very few studies have explored treatments exclusively for symptom palliation. Cognitive-behavioral strategies may be effective treatment for these symptoms in advanced heart failure. Objective A systemic review was conducted to describe the effect of cognitive-behavioral strategies on pain, dyspnea, fatigue, and sleep disturbance in patients with heart failure. Methods CINAHL, Medline, and PsychINFO were searched from inception through December 2014. Articles were selected for inclusion if they tested a cognitive-behavioral strategy using a quasi-experimental or experimental design, involved a sample of adults with heart failure, and measured pain, dyspnea, fatigue, sleep disturbance, or symptom-related quality of life (QoL). The two authors evaluated study quality, abstracted data elements from each study, and synthesized findings. Results Thirteen articles describing nine unique studies met criteria and were included in the review. Five studies tested relaxation strategies, three tested meditation strategies, and one tested a guided imagery strategy. Seven of the nine studies demonstrated some improvement in symptom outcomes. Relaxation, meditation, guided imagery, or combinations of these strategies resulted in less dyspnea and better sleep compared to attention control or usual care conditions, and reduced pain, dyspnea, fatigue and sleep disturbance within treatment groups (pre- to post-treatment). Symptom-related QoL was improved with meditation compared to attention control and usual care conditions, and improved pre- to post-guided imagery. Conclusions Studies exploring cognitive-behavioral symptom management strategies in heart failure vary in quality and report mixed findings, but indicate potential beneficial effects of relaxation, meditation, and guided imagery on heart failure-related symptoms. Future research should test cognitive-behavioral strategies in rigorously designed efficacy trials, using samples selected for their symptom experience, and measure pain, dyspnea, fatigue, and sleep disturbance outcomes with targeted symptom measures. PMID:26065388

Integrating Substance Abuse Treatment and Criminal Justice Supervision

PubMed Central

Marlowe, Douglas B.

2003-01-01

Proponents of a pure public safety perspective on the drug problem hold that drug-involved offenders require consistent and intensive supervision by criminal justice authorities in order to stay off drugs and out of trouble. In contrast, proponents of a thoroughgoing public health perspective commonly argue that clients perform better if they are left alone to develop an effective therapeutic alliance with counselors. Both may be correct, but with respect to different groups of offenders. One approach has shown consistent promise for reducing drug use and criminal recidivism: an integrated public health-public safety strategy that combines community-based drug abuse treatment with ongoing criminal justice supervision. This article presents promising findings from programs implementing this strategy and discusses best treatment practices to meet the needs of both low-risk and high-risk clients. PMID:18552716

Therapeutic strategies for allergic diseases

NASA Astrophysics Data System (ADS)

Barnes, Peter J.

1999-11-01

Many drugs are now in development for the treatment of atopic diseases, including asthma, allergic rhinitis and atopic dermatitis. These treatments are based on improvements in existing therapies or on a better understanding of the cellular and molecular mechanisms involved in atopic diseases. Although most attention has been focused on asthma, treatments that inhibit the atopic disease process would have application to all atopic diseases, as they often coincide. Most of the many new therapies in development are aimed at inhibiting components of the allergic inflammatory response, but in the future there are real possibilities for the development of preventative and even curative treatments.

Idiopathic Hypersomnia.

PubMed

Trotti, Lynn Marie

2017-09-01

Idiopathic hypersomnia (IH) is a chronic neurologic disorder of daytime sleepiness, accompanied by long sleep times, unrefreshing sleep, difficulty in awakening, cognitive dysfunction, and autonomic symptoms. The cause is unknown; a genetic predisposition is suggested. Autonomic, inflammatory, or immune dysfunction has been proposed. Diagnosis involves a clinical history and objective testing. There are no approved treatments for IH, but modafinil is typically considered first-line. A substantial fraction of patients with IH are refractory or intolerant to standard treatments, and different treatment strategies using novel therapeutics are necessary. Even with current treatment options, quality of life and safety may remain impaired. Copyright © 2017 Elsevier Inc. All rights reserved.

Liposomal cytarabine in prophylaxis or curative treatment of central nervous system involvement in Burkitt leukemia/lymphoma.

PubMed

Segot, Amandine; Raffoux, Emmanuel; Lengline, Etienne; Thieblemont, Catherine; Dombret, Hervé; Boissel, Nicolas; Cluzeau, Thomas

2015-11-01

In recent years, the outcome of Burkitt leukemia/lymphoma (BL) has improved significantly. Central nervous system (CNS) involvement continues to be a poor prognostic indicator. High doses of intravenous polychemotherapy, intrathecal chemotherapy, and cranio-spinal radiation therapy are used by numerous groups. Majority of patients are cured after this strategy. The next challenge is to decrease toxicities of treatment, including long-term toxicities secondary to cranio-spinal radiation therapy observed in these cured patients. Liposomal cytarabine could be a good alternative to cranio-spinal radiation therapy as already reported in acute lymphoblastic leukemia. We report here eleven patients treated in our center for BL, with liposomal cytarabine instead of cranio-spinal radiation therapy as prophylactic or curative treatment for CNS involvement. Treatment was safe with no short-term grade >3 adverse events. Moreover, no long-term side effects and no impact on outcome were observed. We conclude that LC could be a good option to decrease short/long-term side effects of cranio-spinal radiation therapy in BL and could be evaluated in a future clinical trial.

Effects of silvicultural treatments on forest birds in the Rocky Mountains: implications and management recommendations

Treesearch

Richard L. Hutto; Sallie J. Hejl; Charles R. Preston; Deborah M. Finch

1993-01-01

The short-term effects of timber harvesting practices on landbird species vary widely among species. Thus, the maintenance of populations of all species will require a long-term management strategy that involves maintenance of a variety of habitats over a broad landscape.

The need to include animal protection in public health policies.

PubMed

Akhtar, Aysha

2013-11-01

Many critical public health issues require non-traditional approaches. Although many novel strategies are used, one approach not widely applied involves improving the treatment of animals. Emerging infectious diseases are pressing public health challenges that could benefit from improving the treatment of animals. Other human health issues, that overlap with animal treatment issues, and that warrant further exploration, are medical research and domestic violence. The diverse nature of these health issues and their connection with animal treatment suggest that there may be other similar intersections. Public health would benefit by including the treatment of animals as a topic of study and policy development.

Cost-Effectiveness of a Community Pharmacist-Led Sleep Apnea Screening Program - A Markov Model.

PubMed

Perraudin, Clémence; Le Vaillant, Marc; Pelletier-Fleury, Nathalie

2013-01-01

Despite the high prevalence and major public health ramifications, obstructive sleep apnea syndrome (OSAS) remains underdiagnosed. In many developed countries, because community pharmacists (CP) are easily accessible, they have been developing additional clinical services that integrate the services of and collaborate with other healthcare providers (general practitioners (GPs), nurses, etc.). Alternative strategies for primary care screening programs for OSAS involving the CP are discussed. To estimate the quality of life, costs, and cost-effectiveness of three screening strategies among patients who are at risk of having moderate to severe OSAS in primary care. Markov decision model. Published data. Hypothetical cohort of 50-year-old male patients with symptoms highly evocative of OSAS. The 5 years after initial evaluation for OSAS. Societal. Screening strategy with CP (CP-GP collaboration), screening strategy without CP (GP alone) and no screening. Quality of life, survival and costs for each screening strategy. Under almost all modeled conditions, the involvement of CPs in OSAS screening was cost effective. The maximal incremental cost for "screening strategy with CP" was about 455€ per QALY gained. Our results were robust but primarily sensitive to the treatment costs by continuous positive airway pressure, and the costs of untreated OSAS. The probabilistic sensitivity analysis showed that the "screening strategy with CP" was dominant in 80% of cases. It was more effective and less costly in 47% of cases, and within the cost-effective range (maximum incremental cost effectiveness ratio at €6186.67/QALY) in 33% of cases. CP involvement in OSAS screening is a cost-effective strategy. This proposal is consistent with the trend in Europe and the United States to extend the practices and responsibilities of the pharmacist in primary care.

Radiation-induced vaginal stenosis: current perspectives

PubMed Central

Morris, Lucinda; Do, Viet; Chard, Jennifer; Brand, Alison H

2017-01-01

Treatment of gynecological cancer commonly involves pelvic radiation therapy (RT) and/or brachytherapy. A commonly observed side effect of such treatment is radiation-induced vaginal stenosis (VS). This review analyzed the incidence, pathogenesis, clinical manifestation(s) and assessment and grading of radiation-induced VS. In addition, risk factors, prevention and treatment options and follow-up schedules are also discussed. The limited available literature on many of these aspects suggests that additional studies are required to more precisely determine the best management strategy of this prevalent group after RT. PMID:28496367

Nanomedicine Strategies to Target Tumor-Associated Macrophages

PubMed Central

Binnemars-Postma, Karin; Storm, Gert; Prakash, Jai

2017-01-01

In recent years, the influence of the tumor microenvironment (TME) on cancer progression has been better understood. Macrophages, one of the most important cell types in the TME, exist in different subtypes, each of which has a different function. While classically activated M1 macrophages are involved in inflammatory and malignant processes, activated M2 macrophages are more involved in the wound-healing processes occurring in tumors. Tumor-associated macrophages (TAM) display M2 macrophage characteristics and support tumor growth and metastasis by matrix remodeling, neo-angiogenesis, and suppressing local immunity. Due to their detrimental role in tumor growth and metastasis, selective targeting of TAM for the treatment of cancer may prove to be beneficial in the treatment of cancer. Due to the plastic nature of macrophages, their activities may be altered to inhibit tumor growth. In this review, we will discuss the therapeutic options for the modulation and targeting of TAM. Different therapeutic strategies to deplete, inhibit recruitment of, or re-educate TAM will be discussed. Current strategies for the targeting of TAM using nanomedicine are reviewed. Passive targeting using different nanoparticle systems is described. Since TAM display a number of upregulated surface proteins compared to non-TAM, specific targeting using targeting ligands coupled to nanoparticles is discussed in detail. PMID:28471401

Persisting eicosanoid pathways in rheumatic diseases.

PubMed

Korotkova, Marina; Jakobsson, Per-Johan

2014-04-01

An unmet clinical need exists for early treatment of rheumatic diseases and improved treatment strategies that can better maintain remission with reduced ongoing subclinical inflammation and bone destruction. Eicosanoids form one of the most complex networks in the body controlling many physiological and pathophysiological processes, including inflammation, autoimmunity and cancer. Persisting eicosanoid pathways are thought to be involved in the development of rheumatic diseases, and targeting this pathway might enable improved treatment strategies. Several enzymes of the arachidonic acid cascade as well as eicosanoid receptors (all part of the eicosanoid pathway) are today well-recognized targets for anti-inflammatory drugs that can reduce symptoms of inflammation in rheumatic diseases. In this Review, we outline the evidence supporting pivotal roles of eicosanoid signalling in the pathogenesis of rheumatic diseases and discuss findings from studies in animals and humans. We focus first on rheumatoid arthritis and discuss the upregulation of the cyclooxygenase and lipoxygenase pathways as most data are available in this condition. Research into the roles of eicosanoids in other rheumatic diseases (osteoarthritis, idiopathic inflammatory myopathies, systemic lupus erythematosus and gout) is also progressing rapidly and is discussed. Finally, we summarize the prospects of targeting eicosanoid pathways as anti-inflammatory treatment strategies for patients with rheumatic diseases.

Psychotherapy in the overall management strategy for social anxiety disorder.

PubMed

Shear, M K; Beidel, D C

1998-01-01

Cognitive-behavioral therapies (CBTs) are effective treatments for social anxiety disorder/social phobia. Although a variety of procedures are included under the term cognitive-behavioral treatment, it is, however, clear that the key factor influencing treatment outcome for social anxiety disorder is exposure to feared situations. Two formalized CBT programs are cognitive-behavioral group therapy (CBGT) and social effectiveness training (SET). They both involve exposure, but differ in that CBGT focuses on correction of cognitive errors, whereas SET uses social skills training in addition to exposure to feared social situations. CBGT is more efficacious than a psychological placebo and has shown efficacy comparable to that of phenelzine in a double-blind, placebo-controlled study. The onset of effect of phenelzine was more rapid, whereas the effect of CBGT was more sustained. The major component of SET, imaginal and/or in vivo exposure, has been demonstrated to be more effective than pill placebo or the beta-blocker atenolol. Many questions remain regarding CBT strategies and their place in the overall management of patients with social anxiety disorder. Depending upon the particular patient profile, various combinations of drug and/or CBT may prove to be the optimal treatment strategy.

Simultaneous Treatment with Subcutaneous Injection of Golimumab and Intra-articular Injection of Triamcinolone Acetonide (K-Method) in Patients with Rheumatoid Arthritis Undergoing Switching of Biologics: Retrospective Case–Control Study

PubMed Central

Kanbe, Katsuaki; Chiba, Junji; Inoue, Yasuo; Taguchi, Masashi; Yabuki, Akiko; Deguchi, Tomohiko

2016-01-01

BACKGROUND Tight control of severe rheumatoid arthritis (RA) in patients with high disease activity, even when using biologics, is sometimes difficult using a treat-to-target strategy. Switching from one biologic to another is associated with lower efficacy than that in treatment-naive cases. We developed the K-method that involves simultaneous treatment with golimumab and intra-articular joint injection of triamcinolone acetonide (TA) in patients undergoing switching of biologics. We performed this retrospective case–control study to investigate the efficacy of achieving an immediate treatment response using the K-method. METHODS This study involved 20 patients with RA (control group, 10 patients; K-method group, 10 patients). Patients in the control group were switched to golimumab from other biologics without intra-articular injection of TA. The K-method involved injection of 1 mL of TA (40 mg/mL) and 2 mL of 1% lidocaine hydrochloride into swollen or painful joints on the same day as golimumab treatment. A quick response one day after treatment was compared between the two groups according to the disease activity score 28 based on C-reactive protein (DAS28 CRP), clinical disease activity index (CDAI), simplified disease activity index (SDAI), European League Against Rheumatism (EULAR) response, and remission rate. These parameters were investigated for 24 weeks. RESULTS The K-method group showed significant improvements in DAS28 CRP, CDAI, and SDAI at one day, 12 weeks, and 24 weeks compared with the control group. The number of swollen and tender joints and the patient and doctor global visual analog scale scores were also significantly different between the two groups. The remission rates based on DAS28 CRP were 30% at one day, 50% at 12 weeks, and 60% at 24 weeks in the K-method group. The EULAR good/moderate response rates were 80% at one day, 90% at 12 weeks, and 90% at 24 weeks in the K-method group; however, these rates were only 10%, 40%, and 40%, respectively, in the control group. No adverse events occurred in either group. CONCLUSION Simultaneous treatment with biologics and intra-articular injection of TA is useful for cases involving switching of biologics for RA. This strategy is safe and practical for RA treatment. PMID:27081319

Involving Patients and Families in the Analysis of Suicides, Suicide Attempts, and Other Sentinel Events in Mental Healthcare: A Qualitative Study in The Netherlands.

PubMed

Bouwman, Renée; de Graaff, Bert; de Beurs, Derek; van de Bovenkamp, Hester; Leistikow, Ian; Friele, Roland

2018-05-29

Involving patients and families in mental healthcare is becoming more commonplace, but little is known about how they are involved in the aftermath of serious adverse events related to quality of care (sentinel events, including suicides). This study explores the role patients and families have in formal processes after sentinel events in Dutch mental healthcare. We analyzed the existing policies of 15 healthcare organizations and spoke with 35 stakeholders including patients, families, their counselors, the national regulator, and professionals. Respondents argue that involving patients and families is valuable to help deal with the event emotionally, provide additional information, and prevent escalation. Results indicate that involving patients and families is only described in sentinel event policies to a limited extent. In practice, involvement consists mostly of providing aftercare and sharing information about the event by providers. Complexities such as privacy concerns and involuntary admissions are said to hinder involvement. Respondents also emphasize that involvement should not be obligatory and stress the need for patients and families to be involved throughout the process of treatment. There is no one-size-fits-all strategy for involving patients and families after sentinel events. The first step seems to be early involvement during treatment process itself.

Delving into foot mechanics and related problems.

PubMed

Zanni, Guido R; Wick, Jeannette Y

2011-12-01

Foot problems are common in elders, stemming from age-related podiatric mechanical problems or disease-induced pathology. Common mechanical problems include hammertoe, arthritis, bunions, and metatarsalgia. Disease-induced conditions include onychomycosis, athlete's foot, plantar warts, gout, and diabetes. Treatment is case-specific and often involves multiple interventions, including lifestyle changes. Prevention and treatment strategies are presented. Patient education on proper foot care is effective.When patients are unable to reach or see their feet, staff assumes responsibility for foot care.

Case Report: Evaluation strategies and cognitive intervention: the case of a monovular twin child affected by selective mutism

PubMed Central

Capobianco, Micaela; Cerniglia, Luca

2018-01-01

The present work describes the assessment process, evaluation strategies, and cognitive intervention on a 9 years old child with selective mutism (SM), a monovular twin of a child also affected by mutism. Currently, the cognitive behavioral multimodal treatment seems the most effective therapeutic approach for children diagnosed with selective mutism (Capobianco & Cerniglia, 2018). The illustrated case confirms the role of biological factors involved in mutacic disorder but also highlights the importance of environmental influences in the maintenance of the disorder with respect to relational and contextual dynamics (e.g. complicity between sisters, family relationships). The article discusses furthermore the importance of an early diagnosis as a predictor of positive treatment outcomes. PMID:29568498

Case Report: Evaluation strategies and cognitive intervention: the case of a monovular twin child affected by selective mutism.

PubMed

Capobianco, Micaela; Cerniglia, Luca

2018-01-01

The present work describes the assessment process, evaluation strategies, and cognitive intervention on a 9 years old child with selective mutism (SM), a monovular twin of a child also affected by mutism. Currently, the cognitive behavioral multimodal treatment seems the most effective therapeutic approach for children diagnosed with selective mutism (Capobianco & Cerniglia, 2018). The illustrated case confirms the role of biological factors involved in mutacic disorder but also highlights the importance of environmental influences in the maintenance of the disorder with respect to relational and contextual dynamics (e.g. complicity between sisters, family relationships). The article discusses furthermore the importance of an early diagnosis as a predictor of positive treatment outcomes.

The importance of pro-inflammatory signaling in neonatal NEC

PubMed Central

Frost, Brandy L.; Jilling, Tamas; Caplan, Michael S.

2008-01-01

Despite modern medical advances, necrotizing enterocolitis (NEC) remains a significant cause of morbidity and mortality in neonatal intensive care units, affecting 10 percent of premature neonates born weighing less than 1500 grams. Although many advances have been made in the understanding of this disease, the etiology and pathophysiology remain incompletely understood, and treatment is limited to supportive care. In recent years, studies have focused on the role of the inflammatory cascade and its’ impact on the disease process, and investigators are evaluating strategies to attenuate inflammatory signaling that might prevent and/or ameliorate neonatal NEC. In this review, we examine the key points in the signaling pathways involved in NEC, and potential strategies for prevention and treatment of this dreaded disease. PMID:18346533

High-performance parallel analysis of coupled problems for aircraft propulsion

NASA Technical Reports Server (NTRS)

Felippa, C. A.; Farhat, C.; Lanteri, S.; Gumaste, U.; Ronaghi, M.

1994-01-01

Applications are described of high-performance parallel, computation for the analysis of complete jet engines, considering its multi-discipline coupled problem. The coupled problem involves interaction of structures with gas dynamics, heat conduction and heat transfer in aircraft engines. The methodology issues addressed include: consistent discrete formulation of coupled problems with emphasis on coupling phenomena; effect of partitioning strategies, augmentation and temporal solution procedures; sensitivity of response to problem parameters; and methods for interfacing multiscale discretizations in different single fields. The computer implementation issues addressed include: parallel treatment of coupled systems; domain decomposition and mesh partitioning strategies; data representation in object-oriented form and mapping to hardware driven representation, and tradeoff studies between partitioning schemes and fully coupled treatment.

Molecular Imaging: Current Status and Emerging Strategies

PubMed Central

Pysz, Marybeth A.; Gambhir, Sanjiv S.; Willmann, Jürgen K.

2011-01-01

In vivo molecular imaging has a great potential to impact medicine by detecting diseases in early stages (screening), identifying extent of disease, selecting disease- and patient-specific therapeutic treatment (personalized medicine), applying a directed or targeted therapy, and measuring molecular-specific effects of treatment. Current clinical molecular imaging approaches primarily use PET- or SPECT-based techniques. In ongoing preclinical research novel molecular targets of different diseases are identified and, sophisticated and multifunctional contrast agents for imaging these molecular targets are developed along with new technologies and instrumentation for multimodality molecular imaging. Contrast-enhanced molecular ultrasound with molecularly-targeted contrast microbubbles is explored as a clinically translatable molecular imaging strategy for screening, diagnosing, and monitoring diseases at the molecular level. Optical imaging with fluorescent molecular probes and ultrasound imaging with molecularly-targeted microbubbles are attractive strategies since they provide real-time imaging, are relatively inexpensive, produce images with high spatial resolution, and do not involve exposure to ionizing irradiation. Raman spectroscopy/microscopy has emerged as a molecular optical imaging strategy for ultrasensitive detection of multiple biomolecules/biochemicals with both in vivo and ex vivo versatility. Photoacoustic imaging is a hybrid of optical and ultrasound modalities involving optically-excitable molecularly-targeted contrast agents and quantitative detection of resulting oscillatory contrast agent movement with ultrasound. Current preclinical findings and advances in instrumentation such as endoscopes and microcatheters suggest that these molecular imaging modalities have numerous clinical applications and will be translated into clinical use in the near future. PMID:20541650

Deviant adolescent subcultures: assessment strategies and clinical interventions.

PubMed

Clark, C M

1992-01-01

Alienation is a contributing factor in adolescents' participation in Satanism, the neo-Nazi skinhead movement, and violent street gangs. Many of their needs are met by gang and/or cult affiliation, including a sense of belonging, self-worth, companionship, and excitement. Emphasizing prevention may minimize deviant subculture involvement, but some adolescents require clinical intervention, ranging from a few outpatient sessions to lengthy inpatient hospitalization. Therapists must be knowledgeable about adolescents' involvement, empathic to their circumstances, and sophisticated in the approach to treatment.

Recovery from cannabis use disorders: Abstinence versus moderation and treatment-assisted recovery versus natural recovery.

PubMed

Stea, Jonathan N; Yakovenko, Igor; Hodgins, David C

2015-09-01

The present study of recovery from cannabis use disorders was undertaken with 2 primary objectives that address gaps in the literature. The first objective was to provide an exploratory portrait of the recovery process from cannabis use disorders, comparing individuals who recovered naturally with those who were involved in treatment. The second objective was to explore systematically the similarities and differences between abstinence and moderation recoveries. Adults who have recovered from a cannabis use disorder were recruited in the community (N = 119). The abstinence and treatment-assisted participants exhibited higher levels of lifetime cannabis problem severity than the moderation and natural recovery participants, respectively. As well, cognitive factors were identified as the most useful strategies for recovery (e.g., thinking about benefits and negative consequences of cannabis), followed by behavioral factors (e.g., avoidance of triggers for use and high-risk situations). Findings lend further support to the effectiveness of cognitive, motivational, and behavioral strategies as helpful actions and maintenance factors involved in the recovery process. The findings also generally support the idea that cannabis use disorders lie on a continuum of problem severity, with moderation and natural recoveries more likely to occur at the lower end of the continuum and abstinence and treatment-assisted recoveries more likely to occur at the upper end. (c) 2015 APA, all rights reserved).

Involvement of Fathers in Pediatric Obesity Treatment and Prevention Trials: A Systematic Review.

PubMed

Morgan, Philip J; Young, Myles D; Lloyd, Adam B; Wang, Monica L; Eather, Narelle; Miller, Andrew; Murtagh, Elaine M; Barnes, Alyce T; Pagoto, Sherry L

2017-02-01

Despite their important influence on child health, it is assumed that fathers are less likely than mothers to participate in pediatric obesity treatment and prevention research. This review investigated the involvement of fathers in obesity treatment and prevention programs targeting children and adolescents (0-18 years). A systematic review of English, peer-reviewed articles across 7 databases. Retrieved records included at least 1 search term from 2 groups: "participants" (eg, child*, parent*) and "outcomes": (eg, obes*, diet*). Randomized controlled trials (RCTs) assessing behavioral interventions to prevent or treat obesity in pediatric samples were eligible. Parents must have "actively participated" in the study. Two authors independently extracted data using a predefined template. The search retrieved 213 eligible RCTs. Of the RCTs that limited participation to 1 parent only (n = 80), fathers represented only 6% of parents. In RCTs in which participation was open to both parents (n = 133), 92% did not report objective data on father involvement. No study characteristics moderated the level of father involvement, with fathers underrepresented across all study types. Only 4 studies (2%) suggested that a lack of fathers was a possible limitation. Two studies (1%) reported explicit attempts to increase father involvement. The review was limited to RCTs published in English peer-reviewed journals over a 10-year period. Existing pediatric obesity treatment or prevention programs with parent involvement have not engaged fathers. Innovative strategies are needed to make participation more accessible and engaging for fathers. Copyright © 2017 by the American Academy of Pediatrics.

Prosthetic joint infection caused by Granulicatella adiacens: a case series and review of literature.

PubMed

Quénard, Fanny; Seng, Piseth; Lagier, Jean-Christophe; Fenollar, Florence; Stein, Andreas

2017-06-23

Bone and joint infection involving Granulicatella adiacens is rare, and mainly involved in cases of bacteremia and infectious endocarditis. Here we report three cases of prosthetic joint infection involving G. adiacens that were successfully treated with surgery and prolonged antimicrobial treatment. We also review the two cases of prosthetic joint infection involving G. adiacens that are reported in the literature. Not all five cases of prosthetic joint infection caused by G. adiacens were associated with bacteremia or infectious endocarditis. Dental care before the onset of infection was observed in two cases. The median time delay between arthroplasty implantation and the onset of infection was of 4 years (ranging between 2 and 10 years). One of our cases was identified with 16srRNA gene sequencing, one case with MALDI-TOF mass spectrometry, and one case with both techniques. Two literature cases were diagnosed by 16srRNA gene sequencing. All five cases were cured after surgery including a two-stage prosthesis exchange in three cases, a one-stage prosthesis exchange in one case, and debridement, antibiotics, irrigation, and retention of the prosthesis in one case, and prolonged antimicrobial treatment. Prosthetic joint infection involving G. adiacens is probably often dismissed due to difficult culture or misdiagnosis, in particular in the cases of polymicrobial infection. Debridement, antibiotics, irrigation, and retention of the prosthesis associated with prolonged antimicrobial treatment (≥ 8 weeks) should be considered as a treatment strategy for prosthetic joint infection involving G. adiacens.

A Review and Update of Treatment Options and Controversies in the Management of Hepatocellular Carcinoma.

PubMed

Dhir, Mashaal; Melin, Alyson A; Douaiher, Jeffrey; Lin, Chi; Zhen, Weining Ken; Hussain, Shahid M; Geschwind, Jean-Francois H; Doyle, Maria B Majella; Abou-Alfa, Ghassan K; Are, Chandrakanth

2016-06-01

To review the current management, outline recent advances and address controversies in the management of hepatocellular carcinoma (HCC). The treatment of HCC is multidisciplinary involving hepatologists, surgeons, medical oncologists, radiation oncologists, radiologists, interventional radiologists, and other disciplines. Each of these disciplines brings its unique perspective and differing opinions that add to controversies in the management of HCC. A focused literature review was performed to identify recent studies on the management of HCC and thereby summarize relevant information on the various therapeutic modalities and controversies involved in the treatment of HCC. The main treatment algorithms continue to rely on hepatic resection or transplantation with controversies involving patients harboring early stage disease and borderline hepatic function. The other treatment strategies include locoregional therapies, radiation, and systemic therapy used alone or in combination with other treatment modalities. Recent advances in locoregional therapies, radiation, and systemic therapies have provided better therapeutic options with curative intent potential for some locoregional therapies. Further refinements in combination therapies such as algorithms consisting of locoregional therapies and systemic or radiation therapies are likely to add additional options and improve survival. The management of HCC has witnessed significant strides with advances in existing options and introduction of several new treatment modalities of various combinations. Further refinements in these treatment options combined with enrollment in clinical trials are essential to improve the management and outcomes of patients with HCC.

Old treatments for new insights and strategies: proposed management in adults and children with alkaptonuria.

PubMed

Arnoux, Jean-Baptiste; Le Quan Sang, Kim-Hanh; Brassier, Anais; Grisel, Coraline; Servais, Aude; Wippf, Julien; Dubois, Sandrine; Sireau, Nicolas; Job-Deslandre, Chantal; Ranganath, Lakshminarayan; de Lonlay, Pascale

2015-09-01

Alkaptonuria (AKU) is caused by deficiency of the enzyme homogentisate 1,2 dioxygenase. It results in an accumulation of homogentisate which oxidizes spontaneously to benzoquinone acetate, a highly oxidant compound, which polymerises to a melanin-like structure, in a process called ochronosis. Asymptomatic during childhood, this accumulation will lead from the second decade of life to a progressive and severe spondylo-arthopathy, associated with multisystem involvement: osteoporosis/fractures, stones (renal, prostatic, gall bladder, salivary glands), ruptures of tendons/muscle/ligaments, renal failure and aortic valve disease. The pathophysiological mechanisms of AKU remain poorly understood, but recent advances lead us to reconsider the treatment strategy in AKU patients. Besides the supporting therapies (pain killers, anti-inflammatory drugs, physiotherapy, joints replacements and others), specific therapies have been considered (anti-oxidant, low protein diet, nitisinone), but clinical studies have failed to prove efficiency on the rheumatological lesions of the disease. Here we propose a treatment strategy for children and adults with AKU, based on a review of the latest findings on AKU and lessons from other aminoacipathies, especially tyrosinemias.

Neuroimmune mechanisms of cytokine-induced depression: current theories and novel treatment strategies.

PubMed

Loftis, Jennifer M; Huckans, Marilyn; Morasco, Benjamin J

2010-03-01

The relationships between immune and neural function are an increasingly important area of study for neuropsychiatric disorders, in particular depression. This is exemplified by the growing number of publications on cytokines and depression during the last 10 years, as compared to earlier decades. This review summarizes the current theories and novel treatment strategies for depression, with a focus on cytokine-induced depression. Neuroimmune mechanisms are now viewed as central to the development of depressive symptoms and emerging evidence is beginning to identify the neural circuits involved in cytokine-induced depression. The current diagnostic categories for depression, as defined by the Diagnostic and Statistical Manual of Mental Disorders, however, are not etiologically or biologically derived, and it has been proposed that "depression", likely reflects multiple pathogeneses leading to varying symptom constellations. As we move toward a better biological understanding of depression-related symptom constellations or syndromes, the term "depression" may prove inadequately broad, and an integration of interdisciplinary literatures will increase in importance. Future research should aim to characterize these depression-related symptom constellations or syndromes better with the goal of optimizing treatment strategies. Published by Elsevier Inc.

Treatment of esophageal cancer with radiation therapy -a pan-Chinese survey of radiation oncologists.

PubMed

Zhang, Yun; Liu, Jing; Zhang, Wencheng; Deng, Weiye; Yue, Jinbo

2017-05-23

Lots of controversies were found about the treatment in relation to radiation therapy (RT) for esophageal squamous cell carcinoma (ESCC). We designed a questionnaire of these controversies to do a pan-Chinese survey of radiation oncologists (ROs). For operable ESCC, 53% ROs chose surgery plus postoperative chemoradiotherapy (CRT), while 40% chose preoperative CRT plus surgery. For target volume of postoperative RT, most ROs (92%) would delineate tumor bed plus involved lymph nodes region before surgery. For definitive RT, most ROs (81%) would give patients higher RT dose to 60-65Gy. For radiation target volume, most ROs would give patients prophylactic irradiation of the bilateral superclavicular-lymph nodes region for cervical ESCC (93%), and the left gastric lymph nodes region for lower thoracic ESCC (72%). For the treatment of mediastinal lymph nodes, 72% ROs preferred elective nodal irradiation, while 28% did the involved nodal irradiation. For concurrent chemotherapy regimen, PF (5-Fu + cisplatin) and TP (cisplatin + paclitaxel) were used widely (49% and 46%, respectively). During simulation, four-dimensional computer tomography (4D CT) was not widely used (48%), even for cervical or lower thoracic ESCC (52%). For daily RT delivery, only 66% ROs would perform imaging guidance RT daily. In summary, more controversies existed in the treatment of ESCC with RT in China, including treatment strategy, radiation dose and target contour. Future goals include standardization of treatment strategy, radiation dose, and target contour, and application of 4D CT and daily imaging guidance, and pursuit of randomized trials in Chinese population.

[Integrated intensive treatment of tinnitus: method and initial results].

PubMed

Mazurek, B; Georgiewa, P; Seydel, C; Haupt, H; Scherer, H; Klapp, B F; Reisshauer, A

2005-07-01

In recent years, no major advances have been made in understanding the mechanisms underlying the development of tinnitus. Hence, the present therapeutic strategies aim at decoupling the subconscious from the perception of tinnitus. Mindful of the lessons drawn from existing tinnitus retraining and desensitisation therapies, a new integrated day hospital strategy of treatment lasting 7-14 days has been developed at the Charité Hospital and is presented in the present paper. The strategy for treating tinnitus in the proximity of patient domicile is designed for patients who feel disturbed in their world of perception and their efficiency due to tinnitus and give evidence of mental and physical strain. In view of the etiologically non-uniform and multiple events connected with tinnitus, consideration was also given to the fact that somatic and psychosocial factors are equally involved. Therefore, therapy should aim at diagnosing and therapeutically influencing those psychosocial factors that reduce the hearing impression to such an extent that the affected persons suffer from strain. The first results of therapy-dependent changes of 46 patients suffering from chronic tinnitus are presented. The data were evaluated before and after 7 days of treatment and 6 months after the end of treatment. Immediately after the treatment, the scores of both the tinnitus questionnaire (Goebel and Hiller) and the subscales improved significantly. These results were maintained during the 6-month post-treatment period and even improved.

Genital and reproductive organ complications of Crohn disease: technical considerations as it relates to perianal disease, imaging features, and implications on management.

PubMed

Kammann, Steven; Menias, Christine; Hara, Amy; Moshiri, Mariam; Siegel, Cary; Safar, Bashar; Brandes, Steven; Shaaban, Akram; Sandrasegaran, Kumar

2017-06-01

A relatively large proportion of patients with Crohn disease (CD) develop complications including abscess formation, stricture, and penetrating disease. A subset of patients will have genital and reproductive organ involvement of CD, resulting in significant morbidity. These special circumstances create unique management challenges that must be tailored to the activity, location, and extent of disease. Familiarity with the epidemiology, pathogenesis, imaging features, and treatment strategies for patients with genital CD can aid imaging diagnoses and guide appropriate patient management. The purpose of this study is to illustrate the spectrum of CD in the genital tract and reproductive organs and discuss the complex management strategies in these patients as it relates to imaging. Given the impact on patient outcome and treatment planning, familiarity with the epidemiology, pathogenesis, imaging features, and treatment of patients with genital Crohn disease can aid radiologic diagnoses and guide appropriate patient management.

Position statement: a clinical approach to the management of adult non-neurogenic overactive bladder.

PubMed

Chung, Eric; Lee, Dominic; Gani, Johan; Gillman, Michael; Maher, Christopher; Brennan, Janelle; Johns Putra, Lydia; Ahmad, Laura; Chan, Lewis Lw

2018-01-15

Overactive bladder (OAB) is a highly prevalent medical condition that has an adverse impact on various health-related quality-of-life domains, including a significant psychosocial and financial burden. This position statement, formulated by members of the Urological Society of Australia and New Zealand and the UroGynaecological Society of Australasia, summarises the current recommendations for clinical diagnosis and treatment strategies in patients with non-neurogenic OAB, and guides clinicians in the decision-making process for managing the condition using evidence-based medicine. Main recommendations: Diagnosis and initial management should be based on thorough clinical history, examination and basic investigations to exclude underlying treatable causes such as urinary tract infection and urological malignancy. Initial treatment strategies for OAB involve conservative management with behavioural modification and bladder retraining. Second-line management involves medical therapy using anticholinergic or β3 agonist drugs provided there is adequate assessment of bladder emptying. If medical therapy is unsuccessful, further investigations with urodynamic studies and cystourethroscopy are recommended to guide further treatment. Intravesical botulinum toxin and sacral neuromodulation should be considered in medical refractory OAB. Changes in management as a result of this statement: OAB is a constellation of urinary symptoms and is a chronic condition with a low likelihood of cure; managing patient expectations is essential because OAB is challenging to treat. At present, the exact pathogenesis of OAB remains unclear and it is likely that there are multiple factors involved in this disease complex. Current medical treatment remains far from ideal, although minimally invasive surgery can be effective. Further research into the pathophysiology of this common condition will hopefully guide future developments in disease management.

Individual Specialist versus Group Preparation for a Computer Programming Contest Involving Secondary Students

ERIC Educational Resources Information Center

McAllister, Deborah A.

1994-01-01

This dissertation investigates the effects of two different grouping strategies on secondary students concerning their preparation for, and performance at, a computer programming contest. Students were divided into two groups, experimental and control, for a 3-week treatment, followed by the contest. Students in the experimental group became…

Management of complex orbital fractures.

PubMed

Bhatti, N; Kanzaria, A; Huxham-Owen, N; Bridle, C; Holmes, S

2016-09-01

The treatment of orbital injuries has evolved considerably over the last two decades. We describe strategies involved in the emergency management of orbital injuries, the use of imaging, preformed and customised materials for reconstruction, and endoscopic techniques. Copyright © 2016 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Personalized Strategies to Activate and Empower Patients in Health Care and Reduce Health Disparities

ERIC Educational Resources Information Center

Chen, Jie; Mullins, C. Daniel; Novak, Priscilla; Thomas, Stephen B.

2016-01-01

Designing culturally sensitive personalized interventions is essential to sustain patients' involvement in their treatment and encourage patients to take an active role in their own health and health care. We consider patient activation and empowerment as a cyclical process defined through patient accumulation of knowledge, confidence, and…

Treatment of an Anonymous Recipient: Solid-Waste Management Simulation Game

ERIC Educational Resources Information Center

Wu, Ko-Chiu; Huang, Po-Yuan

2015-01-01

This study developed a game simulation based on problem solving in the management of urban waste. We then investigated the factors affecting the decisions made by players. During gameplay, the players sought to guide the development of a city via management strategies involving a balance of economic growth and environmental protection. Nature…

Olfactory epithelium: Cells, clinical disorders, and insights from an adult stem cell niche

PubMed Central

Choi, Rhea

2018-01-01

Disorders causing a loss of the sense of smell remain a therapeutic challenge. Basic research has, however, greatly expanded our knowledge of the organization and function of the olfactory system. This review describes advances in our understanding of the cellular components of the peripheral olfactory system, specifically the olfactory epithelium in the nose. The article discusses recent findings regarding the mechanisms involved in regeneration and cellular renewal from basal stem cells in the adult olfactory epithelium, considering the strategies involved in embryonic olfactory development and insights from research on other stem cell niches. In the context of clinical conditions causing anosmia, the current view of adult olfactory neurogenesis, tissue homeostasis, and failures in these processes is considered, along with current and future treatment strategies. Level of Evidence NA PMID:29492466

Effects of Vanadium-Containing Compounds on Membrane Lipids and on Microdomains Used in Receptor-Mediated Signaling

PubMed Central

Roess, Deborah A.; Smith, Steven M. L.; Winter, Peter; Zhou, Jun; Dou, Ping; Baruah, Bharat; Trujillo, Alejandro M.; Levinger, Nancy E.; Yang, Xioda; Barisas, B. George; Crans, Debbie C.

2011-01-01

There is increasing evidence for the involvement of plasma membrane microdomains in insulin receptor function. Moreover, disruption of these structures, which are typically enriched in sphingomyelin and cholesterol, results in insulin resistance. Treatment strategies for insulin resistance include the use of vanadium compounds which have been shown in animal models to enhance insulin responsiveness. One possible mechanism for insulin-enhancing effects might involve direct effects of vanadium compounds on membrane lipid organization. These changes in lipid organization promote the partitioning of insulin receptors and other receptors into membrane microdomains where receptors are optimally functional. To explore this possibility, we have used several strategies involving vanadium complexes such as [VO2dipic]− (pyridin-2,6-dicarboxylatodioxovanadium(V)), decavanadate (V10O286−, V10), BMOV (bis(maltolato)oxovanadium(IV)) and [VO(saltris)]2 (2-salicylideniminato-2-(hydroxymethyl)-1,3-dihydroxypropane-oxovanadium(V)). Our strategies include an evaluation of interactions between vanadium-containing compounds and model lipid systems, an evaluation of the effects of vanadium compounds on lipid fluidity in erythrocyte membranes, and studies of the effects of vanadium-containing compounds on signaling events initiated by receptors known to use membrane microdomains as signaling platforms. PMID:18729092

Gastrointestinal Behçet's disease: A review

PubMed Central

Skef, Wasseem; Hamilton, Matthew J; Arayssi, Thurayya

2015-01-01

Behçet’s disease (BD) is an idiopathic, chronic, relapsing, multi-systemic vasculitis characterized by recurrent oral and genital aphthous ulcers, ocular disease and skin lesions. Prevalence of BD is highest in countries along the ancient silk road from the Mediterranean basin to East Asia. By comparison, the prevalence in North American and Northern European countries is low. Gastrointestinal manifestations of Behçet’s disease are of particular importance as they are associated with significant morbidity and mortality. Although ileocecal involvement is most commonly described, BD may involve any segment of the intestinal tract as well as the various organs within the gastrointestinal system. Diagnosis is based on clinical criteria - there are no pathognomonic laboratory tests. Methods for monitoring disease activity on therapy are available but imperfect. Evidence-based treatment strategies are lacking. Different classes of medications have been successfully used for the treatment of intestinal BD which include 5-aminosalicylic acid, corticosteroids, immunomodulators, and anti-tumor necrosis factor alpha monoclonal antibody therapy. Like inflammatory bowel disease, surgery is reserved for those who are resistant to medical therapy. A subset of patients have a poor disease course. Accurate methods to detect these patients and the optimal strategy for their treatment are not known at this time. PMID:25852265

A practical review of 'containment' during the influenza A (H1N1): an audit of the flu response centre in Yorkshire and the Humber.

PubMed

Padfield, S; Kemp, M; Saravanan, A; Wensley, A

2012-06-01

During the 'containment' phase of the influenza A (H1N1) pandemic 2009, antivirals were used for treatment and prophylaxis. This audit aimed to review the speed of the process involved in delivering antivirals and to assess whether this was likely to have occurred fast enough to be in keeping with the aims of reducing transmission. Flu Response Centres in each region were tasked with co-ordinating local delivery and all case data were entered into Fluzone (an electronic case management system). All data between 1 June and 2 July in the Yorkshire and Humber region were reviewed. Forty-eight hours from the onset of illness to treatment and prophylaxis were used as reference standards. The median estimate for the earliest point cases could have received treatment was 2 days (95% CI 2-3 days) and the earliest point contacts of cases could have received prophylaxis was 4 days (95% CI 4-5 days). The logistical difficulties of delivering 'containment' according to the national algorithms meant there were significant time delays involved and that this was likely to have reduced the effectiveness of the strategy. This would be important to consider if a 'containment' strategy was to be employed in any future emergency.

Cognitive remediation for adolescents with 22q11 deletion syndrome (22q11DS): a preliminary study examining effectiveness, feasibility, and fidelity of a hybrid strategy, remote and computer-based intervention.

PubMed

Mariano, Margaret A; Tang, Kerri; Kurtz, Matthew; Kates, Wendy R

2015-08-01

22q11DS is a multiple anomaly syndrome involving intellectual and behavioral deficits, and increased risk for schizophrenia. As cognitive remediation (CR) has recently been found to improve cognition in younger patients with schizophrenia, we investigated the efficacy, feasibility, and fidelity of a remote, hybrid strategy, computerized CR program in youth with 22q11DS. A longitudinal design was implemented in which 21 participants served as their own controls. Following an eight month baseline period in which no interventions were provided, cognitive coaches met with participants remotely for CR via video conferencing three times a week over a targeted 8month timeframe and facilitated their progress through the intervention, offering task-specific strategies. A subset of strategies were examined for fidelity. Outcomes were evaluated using a neurocognitive test battery at baseline, pre-treatment and post-treatment. All participants adhered to the intervention. The mean length of the treatment phase was 7.96months. A moderately high correlation (intraclass correlation coefficient, 0.73) was found for amount and type of strategies offered by coaches. Participants exhibited significant improvements (ES=.36-.55, p≤.009) in working memory, shifting attention and cognitive flexibility. All significant models were driven by improvements in pre to post-treatment scores. Based on our preliminary investigation, a remote, hybrid strategy, computerized CR program can be implemented with 22q11DS youth despite geographic location, health, and cognitive deficits. It appears effective in enhancing cognitive skills during the developmental period of adolescence, making this type of CR delivery useful for youth with 22q11DS transitioning into post-school environments. Copyright © 2015 Elsevier B.V. All rights reserved.

Postgenomic strategies in antibacterial drug discovery.

PubMed

Brötz-Oesterhelt, Heike; Sass, Peter

2010-10-01

During the last decade the field of antibacterial drug discovery has changed in many aspects including bacterial organisms of primary interest, discovery strategies applied and pharmaceutical companies involved. Target-based high-throughput screening had been disappointingly unsuccessful for antibiotic research. Understanding of this lack of success has increased substantially and the lessons learned refer to characteristics of targets, screening libraries and screening strategies. The 'genomics' approach was replaced by a diverse array of discovery strategies, for example, searching for new natural product leads among previously abandoned compounds or new microbial sources, screening for synthetic inhibitors by targeted approaches including structure-based design and analyses of focused libraries and designing resistance-breaking properties into antibiotics of established classes. Furthermore, alternative treatment options are being pursued including anti-virulence strategies and immunotherapeutic approaches. This article summarizes the lessons learned from the genomics era and describes discovery strategies resulting from that knowledge.

Risk-adapted treatment and follow-up management in childhood-onset craniopharyngioma.

PubMed

Müller, Hermann L

2016-05-01

Craniopharyngiomas are rare embryonic malformations of the sellar/parasellar region with low histological grade. Here, we review findings on the diagnosis, treatment, clinical course, follow-up, and prognosis of craniopharyngioma patients. Clinical manifestations develop from increased intracranial pressure, anterior visual pathway damage, and hypothalamic/pituitary deficiencies. If the tumor is favorably localized (no anatomical involvement with the hypothalamic and optical structures) therapy of choice is complete resection, meticulously performed to preserve hypothalamic and optic functions. In patients with unfavorable tumor involvement, optimal therapy is limited hypothalamus-sparing surgical strategy, followed by judicious irradiation dosage to minimize recurrences and progression. Surgical lesions and/or anatomical involvement of posterior hypothalamic areas result in serious sequelae, mainly hypothalamic syndrome. Craniopharyngioma is a chronic disease and must be managed as such, providing ongoing care of pediatric and adult patients by experienced multidisciplinary teams in the context of multicenter trials.

Recent advances in photoluminescence detection of fingerprints.

PubMed

Menzel, E R

2001-10-02

Photoluminescence detection of latent fingerprints has over the last quarter century brought about a new level of fingerprint detection sensitivity. The current state of the art is briefly reviewed to set the stage for upcoming new fingerprint processing strategies. These are designed for suppression of background fluorescence from articles holding latent prints, an often serious problem. The suppression of the background involves time-resolved imaging, which is dealt with from the perspective of instrumentation as well as the design of fingerprint treatment strategies. These focus on lanthanide chelates, nanocrystals, and nanocomposites functionalized to label fingerprints.

Preventing Chronic Pain following Acute Pain: Risk Factors, Preventive Strategies, and their Efficacy

PubMed Central

McGreevy, Kai; Bottros, Michael M.; Raja, Srinivasa N.

2011-01-01

Chronic pain is the leading cause of disability in the United States. The transition from acute to persistent pain is thought to arise from maladaptive neuroplastic mechanisms involving three intertwined processes, peripheral sensitization, central sensitization, and descending modulation. Strategies aimed at preventing persistent pain may target such processes. Models for studying preventive strategies include persistent post-surgical pain (PPP), persistent post-trauma pain (PTP) and post-herpetic neuralgia (PHN). Such entities allow a more defined acute onset of tissue injury after which study of the long-term effects is more easily examined. In this review, we examine the pathophysiology, epidemiology, risk factors, and treatment strategies for the prevention of chronic pain using these models. Both pharmacological and interventional approaches are described, as well as a discussion of preventive strategies on the horizon. PMID:22102847

Developing an Integrated, Brief Biobehavioral HIV Prevention Intervention for High-Risk Drug Users in Treatment: The Process and Outcome of Formative Research

PubMed Central

Shrestha, Roman; Altice, Frederick; Karki, Pramila; Copenhaver, Michael

2017-01-01

To date, HIV prevention efforts have largely relied on singular strategies (e.g., behavioral or biomedical approaches alone) with modest HIV risk-reduction outcomes for people who use drugs (PWUD), many of whom experience a wide range of neurocognitive impairments (NCI). We report on the process and outcome of our formative research aimed at developing an integrated biobehavioral approach that incorporates innovative strategies to address the HIV prevention and cognitive needs of high-risk PWUD in drug treatment. Our formative work involved first adapting an evidence-based behavioral intervention—guided by the Assessment–Decision–Administration–Production–Topical experts–Integration–Training–Testing model—and then combining the behavioral intervention with an evidence-based biomedical intervention for implementation among the target population. This process involved eliciting data through structured focus groups (FGs) with key stakeholders—members of the target population (n = 20) and treatment providers (n = 10). Analysis of FG data followed a thematic analysis approach utilizing several qualitative data analysis techniques, including inductive analysis and cross-case analysis. Based on all information, we integrated the adapted community-friendly health recovery program—a brief evidence-based HIV prevention behavioral intervention—with the evidence-based biomedical component [i.e., preexposure prophylaxis (PrEP)], an approach that incorporates innovative strategies to accommodate individuals with NCI. This combination approach—now called the biobehavioral community-friendly health recovery program—is designed to address HIV-related risk behaviors and PrEP uptake and adherence as experienced by many PWUD in treatment. This study provides a complete example of the process of selecting, adapting, and integrating the evidence-based interventions—taking into account both empirical evidence and input from target population members and target organization stakeholders. The resultant brief evidence-based biobehavioral approach could significantly advance primary prevention science by cost-effectively optimizing PrEP adherence and HIV risk reduction within common drug treatment settings. PMID:28553295

Community psychiatric care: from libertarianism to coercion. Moral panic and mental health policy in Britain.

PubMed

Holloway, F

1996-08-01

This article discusses recent developments in mental health policy in Britain, focusing on the move towards compulsory supervision of mentally ill people in the community. It is argued that the desire for compulsion reflects moral panic rather than rational appraisal of the undoubted problems with community mental health care. Alternative strategies involving education of the patient and cares, the deployment of psychological treatments of psychosis and an emphasis on the negotiation of treatment plans, are advocated.

Cost-effectiveness of cardioversion and antiarrhythmic therapy in nonvalvular atrial fibrillation.

PubMed

Catherwood, E; Fitzpatrick, W D; Greenberg, M L; Holzberger, P T; Malenka, D J; Gerling, B R; Birkmeyer, J D

1999-04-20

Physicians managing patients with nonvalvular atrial fibrillation must consider the risks, benefits, and costs of treatments designed to restore and maintain sinus rhythm compared with those of rate control with antithrombotic prophylaxis. To compare the cost-effectiveness of cardioversion, with or without antiarrhythmic agents, with that of rate control plus warfarin or aspirin. A Markov decision-analytic model was designed to simulate long-term health and economic outcomes. Published literature and hospital accounting information. Hypothetical cohort of 70-year-old patients with different baseline risks for stroke. 3 months. Societal. Therapeutic strategies using different combinations of cardioversion alone, cardioversion plus amiodarone or quinidine therapy, and rate control with antithrombotic treatment. Expected costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness. Strategies involving cardioversion alone were more effective and less costly than those not involving this option. For patients at high risk for ischemic stroke (5.3% per year), cardioversion alone followed by repeated cardioversion plus amiodarone therapy on relapse was most cost-effective ($9300 per QALY) compared with cardioversion alone followed by warfarin therapy on relapse. This strategy was also preferred for the moderate-risk cohort (3.6% per year), but the benefit was more expensive ($18,900 per QALY). In the lowest-risk cohort (1.6% per year), cardioversion alone followed by aspirin therapy on relapse was optimal. The choice of optimal strategy and incremental cost-effectiveness was substantially influenced by the baseline risk for stroke, rate of stroke in sinus rhythm, efficacy of warfarin, and costs and utilities for long-term warfarin and amiodarone therapy. Cardioversion alone should be the initial management strategy for persistent nonvalvular atrial fibrillation. On relapse of arrhythmia, repeated cardioversion plus low-dose amiodarone is cost-effective for patients at moderate to high risk for ischemic stroke.

Reconstruction of the mandible bone by treatment of resected bone with pasteurization.

PubMed

Uehara, Masataka; Inokuchi, Tsugio; Sano, Kazuo; Sumita, Yoshinori; Tominaga, Kazuhiro; Asahina, Izumi

2012-11-01

The results of long-term follow-up for reimplantation of the mandibular bone treated with pasteurization are reported. Mandibulectomy was performed for mandibular malignancy in 3 cases. The resected bones were subsequently reimplanted after treatment with pasteurization in 3 cases to eradicate tumor cells involved in the resected bone. Although postoperative infection was observed in 2 of 3 cases, reimplantation of the resected mandibular bone treated by pasteurization was finally successful. Ten to 22 years of follow-up was carried out. Pasteurization was able to devitalize tumor cells involved in the resected bone and to preserve bone-inductive activity. Reimplantation of pasteurization could be a useful strategy for reconstruction of the mandible in patients with mandibular malignancy.

Treatment strategies for childhood noninfectious chronic uveitis: an update.

PubMed

Cantarini, Luca; Simonini, Gabriele; Frediani, Bruno; Pagnini, Ilaria; Galeazzi, Mauro; Cimaz, Rolando

2012-01-01

Uveitis is an inflammatory disorder involving inflammation of the uveal tract. It is classified as anterior, intermediate, posterior or panuveitis, depending on the part of eye affected by the inflammatory process. In children, noninfectious, chronic uveitis is a relatively uncommon but serious disease, with the potential for significant long-term complications and possible blindness. Although frequently associated with an underlying systemic disease, for example, juvenile idiopathic arthritis, a significant number of cases in children show no associated signs or symptoms and are labeled as idiopathic. We reviewed the available literature. Taking into account this evidence, an anti-inflammatory therapy based on an immunomodulatory approach seems a reasonable strategy for noninfectious chronic uveitis, in children as well as in adults. Due to a lack of controlled studies regarding uveitis in children, immunosuppressive strategy is supported only at evidence level III. Our aim is to review the currently available medical strategies for the treatment of childhood sight-threatening chronic uveitis. Uveitis in children can be severe. Methotrexate is the drug of choice for recalcitrant cases, and biologic therapies can be useful in selected situations.

Enrichment Strategies in Pediatric Drug Development: An Analysis of Trials Submitted to the US Food and Drug Administration.

PubMed

Green, Dionna J; Liu, Xiaomei I; Hua, Tianyi; Burnham, Janelle M; Schuck, Robert; Pacanowski, Michael; Yao, Lynne; McCune, Susan K; Burckart, Gilbert J; Zineh, Issam

2017-12-08

Clinical trial enrichment involves prospectively incorporating trial design elements that increase the probability of detecting a treatment effect. The use of enrichment strategies in pediatric drug development has not been systematically assessed. We analyzed the use of enrichment strategies in pediatric trials submitted to the US Food and Drug Administration from 2012-2016. In all, 112 efficacy studies associated with 76 drug development programs were assessed and their overall success rates were 78% and 75%, respectively. Eighty-eight trials (76.8%) employed at least one enrichment strategy; of these, 66.3% employed multiple enrichment strategies. The highest trial success rates were achieved when all three enrichment strategies (practical, predictive, and prognostic) were used together within a single trial (87.5%), while the lowest success rate was observed when no enrichment strategy was used (65.4%). The use of enrichment strategies in pediatric trials was found to be associated with trial and program success in our analysis. © 2017 American Society for Clinical Pharmacology and Therapeutics.

[Impulse control in addiction: a translational perspective].

PubMed

Schmaal, L; Broos, N; Joos, L; Pattij, T; Goudriaan, A E

2013-01-01

Impulsivity is a hallmark of addiction and predicts treatment response and relapse. Impulsivity is, however, a complex construct. Translational cross-species research is needed to give us greater insight into the neurobiology and the role of impulsivity in addiction and to help with the development of new treatment strategies for improving patients' impulse control. To review recent evidence concerning the concept of impulsivity and the role of impulsivity in addiction. The concept and neurobiology of impulsivity are reviewed from a translational perspective. The role of impulsivity in addiction and implications for treatment are discussed. Our recent translational cross-species study indicates that impulsivity is made up of several, separate independent features with partly distinct underlying neurobiological substrates. There are also indications that these features make a unique and independent contribution to separate stages of the addiction cycle. In addition, the improvement of impulse control is a promising new target area for treatments that could lead to better results. However, those involved in developing new treatment strategies will have to take into account the complexity and multidimensional character of impulsivity.

Emerging Drugs for Uveitis

PubMed Central

Larson, Theresa; Nussenblatt, Robert B.; Sen, H. Nida

2010-01-01

Importance of the Field Uveitis is a challenging disease covering both infectious and noninfectious conditions. The current treatment strategies are hampered by the paucity of randomized controlled trials (RCTs) and few trials comparing efficacy of different agents. Areas Covered in this Review This review describes the current and future treatments of uveitis. A literature search was performed in PUBMED from 1965 to 2010 on drugs treating ocular inflammation with emphasis placed on more recent, larger studies. What the Reader Will Gain Readers should gain a basic understanding of current treatment strategies beginning with corticosteroids and transitioning to steroid sparing agents. Steroid sparing agents include the antimetabolites which include methotrexate, azathioprine, and mycophenolate mofetil; the calcineurin inhibitors which include cyclosporine, tacrolimus; alkylating agents which include cyclophosphamide and chlorambucil; and biologics which include the TNF-α inhibitors infliximab, adalimumab, and etanercept; daclizumab, interferon α2a, and rituximab. Take Home Message Newer agents are typically formulated from existing drugs or developed based on new advances in immunology. Future treatment will require a better understanding of the mechanisms involved in autoimmune diseases and better delivery systems in order to provide targeted treatment with minimal side effects. PMID:21210752

Bacteriocins - exploring alternatives to antibiotics in mastitis treatment.

PubMed

Pieterse, Reneé; Todorov, Svetoslav D

2010-07-01

Mastitis is considered to be the most costly disease affecting the dairy industry. Management strategies involve the extensive use of antibiotics to treat and prevent this disease. Prophylactic dosages of antibiotics used in mastitis control programmes could select for strains with resistance to antibiotics. In addition, a strong drive towards reducing antibiotic residues in animal food products has lead to research in finding alternative antimicrobial agents. In this review we have focus on the pathogenesis of the mastitis in dairy cows, existing antibiotic treatments and possible alternative for application of bacteriocins from lactic acid bacteria in the treatment and prevention of this disease.

Implementing stakeholder-informed research in the substance abuse treatment sector: strategies used by Connections, a Canadian knowledge translation and exchange project.

PubMed

Henderson, Joanna; Sword, Wendy; Niccols, Alison; Dobbins, Maureen

2014-05-29

Researcher-stakeholder collaboration has been identified as critical to bridging research and health system change. While collaboration models vary, meaningful stakeholder involvement over time ("integrated knowledge translation") is advocated to improve the relevance of research to knowledge users. This short report describes the integrated knowledge translation efforts of Connections, a knowledge translation and exchange project to improve services for women with substance abuse problems and their children, and implementation barriers and facilitators. Strategies of varying intensities were used to engage diverse stakeholders, including policy makers and people with lived experience, and executive directors, program managers, and service providers from Canadian addiction agencies serving women. Barriers to participation included individual (e.g., interest), organizational (e.g., funding), and system level (e.g., lack of centralized stakeholder database) barriers. Similarly, facilitators included individual (e.g., perceived relevance) and organizational (e.g., support) facilitators, as well as initiative characteristics (e.g., multiple involvement opportunities). Despite barriers, Connections' stakeholder-informed research efforts proved essential for developing clinically relevant and feasible processes, measures, and implementation strategies. Stakeholder-researcher collaboration is possible and robust integrated knowledge translation efforts can be productive. Future work should emphasize developing and evaluating a range of strategies to address stakeholders' knowledge translation needs and to facilitate sustained and meaningful involvement in research.

Evaluation of a decision support strategy for the control of powdery mildew, Erysiphe necator (Schw.) Burr., in grapevine in the central region of Chile.

PubMed

Valdés-Gómez, Héctor; Araya-Alman, Miguel; Pañitrur-De la Fuente, Carolina; Verdugo-Vásquez, Nicolás; Lolas, Mauricio; Acevedo-Opazo, César; Gary, Christian; Calonnec, Agnès

2017-09-01

The primary strategy to control powdery mildew in Chilean vineyards involves periodic fungicide spraying, which may lead to many environmental and human health risks. This study aimed to implement and evaluate the effectiveness and economic feasibility of a novel decision support strategy (DSS) to limit the number of treatments against this pathogen. An experiment was conducted between the 2010 and 2013 seasons in two irrigated vine fields, one containing a cultivar of Cabernet Sauvignon (CS) and the other a cultivar of Chardonnay (CH). The results showed that the DSS effectively controlled powdery mildew in CS and CH vine fields, as evidenced by a disease severity lower than 3%, which was lower than that observed in untreated vines (approximately 10 and 40% for CS and CH respectively). The DS strategy required the application of only 2-3 fungicide treatments per season in key vine phenological stages, and the cost fluctuated between $US 322 and 415 ha -1 , which was 40-60% cheaper than the traditional strategy employed by vine growers. The decision support strategy evaluated in this trial allows a good control of powdery mildew for various types of epidemic with an early and late initiation. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Immunization against Small Ruminant Lentiviruses

PubMed Central

Reina, Ramsés; de Andrés, Damián; Amorena, Beatriz

2013-01-01

Multisystemic disease caused by Small Ruminant Lentiviruses (SRLV) in sheep and goats leads to production losses, to the detriment of animal health and welfare. This, together with the lack of treatments, has triggered interest in exploring different strategies of immunization to control the widely spread SRLV infection and, also, to provide a useful model for HIV vaccines. These strategies involve inactivated whole virus, subunit vaccines, DNA encoding viral proteins in the presence or absence of plasmids encoding immunological adjuvants and naturally or artificially attenuated viruses. In this review, we revisit, comprehensively, the immunization strategies against SRLV and analyze this double edged tool individually, as it may contribute to either controlling or enhancing virus replication and/or disease. PMID:23917352

Programmed death-1 & its ligands: promising targets for cancer immunotherapy.

PubMed

Shrimali, Rajeev K; Janik, John E; Abu-Eid, Rasha; Mkrtichyan, Mikayel; Khleif, Samir N

2015-01-01

Novel strategies for cancer treatment involving blockade of immune inhibitors have shown significant progress toward understanding the molecular mechanism of tumor immune evasion. The preclinical findings and clinical responses associated with programmed death-1 (PD-1) and PD-ligand pathway blockade seem promising, making these targets highly sought for cancer immunotherapy. In fact, the anti-PD-1 antibodies, pembrolizumab and nivolumab, were recently approved by the US FDA for the treatment of unresectable and metastatic melanoma resistant to anticytotoxic T-lymphocyte antigen-4 antibody (ipilimumab) and BRAF inhibitor. Here, we discuss strategies of combining PD-1/PD-ligand interaction inhibitors with other immune checkpoint modulators and standard-of-care therapy to break immune tolerance and induce a potent antitumor activity, which is currently a research area of key scientific pursuit.

TB control programmes: the challenges for Africa.

PubMed

Harries, T

1996-11-01

Governmental neglect of tuberculosis (TB), inadequately managed and inaccurately designed TB control programs, population growth, and the HIV epidemic account for the resurgence of TB in sub-Saharan Africa. The World Health Organization and the International Union against TB and Lung Disease have developed a TB control strategy that aims to reduce mortality, morbidity, and transmission of TB. It aims for an 85% cure rate among detected new cases of smear-positive TB and a 70% rate of detecting existing smear-positive TB cases. The strategy involves the provision of short-course chemotherapy (SCC) to all identified smear-positive TB cases through directly observed treatment (DOTS). SCC treatment regimens for smear-positive pulmonary TB recommended for sub-Saharan African countries are: initial phase = daily administration over 2 months of streptomycin, rifampicin, isoniazid, and pyrazinamide; continuation phase = 3 doses over 4 months of isoniazid and rifampicin or daily administration of thiacetazone and isoniazid or of ethambutol and isoniazid. A TB control policy must be implemented to bring about effective TB control. The essential elements of this policy include political commitment, case detection through passive case-finding, SCC, a regular supply of essential drugs, and a monitoring and evaluation system. Political commitment involves establishing a National TB Control Program to be integrated into the existing health structure. Increased awareness of TB in the community and among health workers and a reference laboratory are needed to make case finding successful. A distribution and logistics system is needed to ensure uninterrupted intake of drugs throughout treatment. These regimens have been very successful and cost-effective but pose several disadvantages (e.g., heavy workload of recommended 3 sputum smear tests). A simplified approach involves 1 initial sputum smear for 6 months; 6-months, intermittent rifampicin-based therapy, 100% DOTS throughout entire treatment course, and ascertainment of treatment completion rates and mortality rates in all patients.

Persistent visceral allodynia in rats exposed to colorectal irradiation is reversed by mesenchymal stromal cell treatment.

PubMed

Durand, Christelle; Pezet, Sophie; Eutamène, Hélène; Demarquay, Christelle; Mathieu, Noëlle; Moussa, Lara; Daudin, Rachel; Holler, Valérie; Sabourin, Jean-Christophe; Milliat, Fabien; François, Agnès; Theodorou, Vassilia; Tamarat, Radia; Benderitter, Marc; Sémont, Alexandra

2015-08-01

Each year, millions of people worldwide are treated for primary or recurrent pelvic malignancies, involving radiotherapy in almost 50% of cases. Delayed development of visceral complications after radiotherapy is recognized in cancer survivors. Therapeutic doses of radiation may lead to the damage of healthy tissue around the tumor and abdominal pain. Because of the lack of experimental models, the underlying mechanisms of radiation-induced long-lasting visceral pain are still unknown. This makes managing radiation-induced pain difficult, and the therapeutic strategies proposed are mostly inefficient. The aim of our study was to develop an animal model of radiation-induced visceral hypersensitivity to (1) analyze some cellular and molecular mechanisms involved and (2) to test a therapeutic strategy using mesenchymal stromal cells (MSCs). Using a single 27-Grays colorectal irradiation in rats, we showed that such exposure induces a persistent visceral allodynia that is associated with an increased spinal sensitization (enhanced p-ERK neurons), colonic neuroplasticity (as increased density of substance P nerve fibers), and colonic mast cell hyperplasia and hypertrophy. Mast cell stabilization by ketotifen provided evidence of their functional involvement in radiation-induced allodynia. Finally, intravenous injection of 1.5 million MSCs, 4 weeks after irradiation, induced a time-dependent reversion of the visceral allodynia and a reduction of the number of anatomical interactions between mast cells and PGP9.5+ nerve fibers. Moreover, unlike ketotifen, MSC treatment has the key advantage to limit radiation-induced colonic ulceration. This work provides new insights into the potential use of MSCs as cellular therapy in the treatment of pelvic radiation disease.

Individual Differences in Working Memory Capacity Predicts Responsiveness to Memory Rehabilitation After Traumatic Brain Injury.

PubMed

Sandry, Joshua; Chiou, Kathy S; DeLuca, John; Chiaravalloti, Nancy D

2016-06-01

To explore how individual differences affect rehabilitation outcomes by specifically investigating whether working memory capacity (WMC) can be used as a cognitive marker to identify who will and will not improve from memory rehabilitation. Post hoc analysis of a randomized controlled clinical trial designed to treat learning and memory impairment after traumatic brain injury (TBI): 2 × 2 between-subjects quasiexperimental design (2 [group: treatment vs control] × 2 [WMC: high vs low]). Nonprofit medical rehabilitation research center. Participants (N=65) with moderate to severe TBI with pre- and posttreatment data. The treatment group completed 10 cognitive rehabilitation sessions in which subjects were taught a memory strategy focusing on learning to use context and imagery to remember information. The placebo control group engaged in active therapy sessions that did not involve learning the memory strategy. Long-term memory percent retention change scores for an unorganized list of words from the California Verbal Learning Test-II. Group and WMC interacted (P=.008, ηp(2)=.12). High WMC participants showed a benefit from treatment compared with low WMC participants. Individual differences in WMC accounted for 45% of the variance in whether participants with TBI in the treatment group benefited from applying the compensatory treatment strategy to learn unorganized information. Individuals with higher WMC showed a significantly greater rehabilitation benefit when applying the compensatory strategy to learn unorganized information. WMC is a useful cognitive marker for identifying participants with TBI who respond to memory rehabilitation with the modified Story Memory Technique. Copyright © 2016 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Beyond the Barriers of Light Penetration: Strategies, Perspectives and Possibilities for Photodynamic Therapy

PubMed Central

Mallidi, Srivalleesha; Anbil, Sriram; Bulin, Anne-Laure; Obaid, Girgis; Ichikawa, Megumi; Hasan, Tayyaba

2016-01-01

Photodynamic therapy (PDT) is a photochemistry based treatment modality that involves the generation of cytotoxic species through the interactions of a photosensitizer molecule with light irradiation of an appropriate wavelength. PDT is an approved therapeutic modality for several cancers globally and in several cases has proved to be effective where traditional treatments have failed. The key parameters that determine PDT efficacy are 1. the photosensitizer (nature of the molecules, selectivity, and macroscopic and microscopic localization etc.), 2. light application (wavelength, fluence, fluence rate, irradiation regimes etc.) and 3. the microenvironment (vascularity, hypoxic regions, stromal tissue density, molecular heterogeneity etc.). Over the years, several groups aimed to monitor and manipulate the components of these critical parameters to improve the effectiveness of PDT treatments. However, PDT is still misconstrued to be a surface treatment primarily due to the limited depths of light penetration. In this review, we present the recent advances, strategies and perspectives in PDT approaches, particularly in cancer treatment, that focus on increasing the 'damage zone' beyond the reach of light in the body. This is enabled by a spectrum of approaches that range from innovative photosensitizer excitation strategies, increased specificity of phototoxicity, and biomodulatory approaches that amplify the biotherapeutic effects induced by photodynamic action. Along with the increasing depth of understanding of the underlying physical, chemical and physiological mechanisms, it is anticipated that with the convergence of these strategies, the clinical utility of PDT will be expanded to a powerful modality in the armamentarium for the management of cancer. PMID:27877247

Family involvement in cancer treatment decision-making: A qualitative study of patient, family, and clinician attitudes and experiences.

PubMed

Laidsaar-Powell, Rebekah; Butow, Phyllis; Bu, Stella; Charles, Cathy; Gafni, Amiram; Fisher, Alana; Juraskova, Ilona

2016-07-01

Little is known about how family are involved in cancer treatment decision-making. This study aimed to qualitatively explore Australian oncology clinicians', patients', and family members' attitudes towards, and experiences of, family involvement in decision-making. Semi-structured interviews were conducted with 30 cancer patients, 33 family members, 10 oncology nurses and 11 oncologists. Framework analysis methods were used. Three main themes were uncovered: (i) how family are involved in the decision-making process: specific behaviours of family across 5 (extended) decision-making stages; (ii) attitudes towards family involvement in the decision-making process: balancing patient authority with the rights of the family; and (iii) factors influencing family involvement: patient, family, cultural, relationship, and decision. This study highlighted many specific behaviours of family throughout the decision-making process, the complex participant attitudes toward retaining patient authority whilst including the family, and insight into influencing factors. These findings will inform a conceptual framework describing family involvement in decision-making. Clinicians could ascertain participant preferences and remain open to the varying forms of family involvement in decision-making. Given the important role of family in the decision-making process, family inclusive consultation strategies are needed. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Anti-Drug Abuse Strategy Report. State of New York. 1993 Update.

ERIC Educational Resources Information Center

New York Governor's Office, Albany. Statewide Anti-Drug Abuse Council.

Research shows a clear link between drug and alcohol use and crime and violence. This report describes progress made in 1993 as a result of New York State's anti-drug abuse agenda and priorities for 1994. Efforts exist in three complementary areas: prevention (preventing people from being involved in substance abuse); treatment (treating those who…

The role of positive emotion and contributions of positive psychology in depression treatment: systematic review.

PubMed

Santos, Veruska; Paes, Flavia; Pereira, Valeska; Arias-Carrión, Oscar; Silva, Adriana Cardoso; Carta, Mauro Giovanni; Nardi, Antonio Egidio; Machado, Sergio

2013-01-01

The present study aims to conduct a systematic review of the literature by checking the impact of positive emotion in the treatment of depression and on the use of strategies of positive psychology which involves positive emotion to treat and reduce symptoms of depression. For this purpose, we conducted searches in databases ISI Web of Knowledge, PsycINFO and PubMed and found a total of 3400 studies. After inclusion application and exclusion criteria, 28 articles remained, presented and discussed in this study. The studies have important relations between humor and positive emotion as well as a significant improvement in signs and symptoms of depression using differents strategies of positive psychology. Another relevant aspect is the preventative character of the proposed interventions by positive psychology by the fact that increase well-being and produce elements such as resilience and coping resources that reduce the recurrent relapses in the treatment of depression. The strategies of positive psychology, such as increasing positive emotions, develop personal strengths: seeking direction, meaning and engagement for the day-to-day life of the patients, appear as potentially tools for the prophylaxis and treatment of depression, helping to reduce signs and symptoms as well as for prevention of relapses.

The Role of Positive Emotion and Contributions of Positive Psychology in Depression Treatment: Systematic Review

PubMed Central

Santos, Veruska; Paes, Flavia; Pereira, Valeska; Arias-Carrión, Oscar; Silva, Adriana Cardoso; Carta, Mauro Giovanni; Nardi, Antonio Egidio; Machado, Sergio

2013-01-01

The present study aims to conduct a systematic review of the literature by checking the impact of positive emotion in the treatment of depression and on the use of strategies of positive psychology which involves positive emotion to treat and reduce symptoms of depression. For this purpose, we conducted searches in databases ISI Web of Knowledge, PsycINFO and PubMed and found a total of 3400 studies. After inclusion application and exclusion criteria, 28 articles remained, presented and discussed in this study. The studies have important relations between humor and positive emotion as well as a significant improvement in signs and symptoms of depression using differents strategies of positive psychology. Another relevant aspect is the preventative character of the proposed interventions by positive psychology by the fact that increase well-being and produce elements such as resilience and coping resources that reduce the recurrent relapses in the treatment of depression. The strategies of positive psychology, such as increasing positive emotions, develop personal strengths: seeking direction, meaning and engagement for the day-to-day life of the patients, appear as potentially tools for the prophylaxis and treatment of depression, helping to reduce signs and symptoms as well as for prevention of relapses. PMID:24358052

A case report of orbital Langerhans cell histiocytosis presenting as a orbital cellulitis.

PubMed

Albert-Fort, M; González-Candial, M

2018-04-08

A 10-year-old girl was seen with a 3-week history of right upper lid swelling and with no other symptoms or fever. There was no recent history of sinusitis, trauma, or previous infection involving the periorbital area, or response to oral antibiotic treatment. Orbital computed tomography showed a lesion involving the upper margin of the orbit, and bone destruction at the orbital roof. Biopsy performed revealed the presence of Langerhans cell Histiocytosis. The lesion was surgically debulked and corticosteroids were used intra-operatively. The lesion responded to treatment. The orbital involvement of Langerhans cell histiocytosis, despite its low incidence, should be considered in the examination of acute peri-orbital swelling. It usually presents as an osteolytic lesion, and it is confirmed with a histological examination and immunohistochemical techniques for CD1a and S100. An interdisciplinary approach is recommended to rule out multifocal or multisystemic diseases, as well as to develop an appropriate treatment strategy. Copyright © 2018 Sociedad Española de Oftalmología. Publicado por Elsevier España, S.L.U. All rights reserved.

Practice variation in the structure of stroke rehabilitation in four rehabilitation centres in the Netherlands.

PubMed

Groeneveld, Iris F; Meesters, Jorit J L; Arwert, Henk J; Roux-Otter, Nienke; Ribbers, Gerard M; van Bennekom, Coen A M; Goossens, Paulien H; Vliet Vlieland, Thea P M

2016-03-01

To describe practice variation in the structure of stroke rehabilitation in 4 specialized multidisciplinary rehabilitation centres in the Netherlands. A multidisciplinary expert group formulated a set of 23 elements concerning the structure of inpatient and outpatient stroke rehabilitation, categorized into 4 domains: admission-related (n = 7), treatment-related (n = 10), client involvement-related (n = 2), and facilities-related (n = 4). In a cross-sectional study in 4 rehabilitation centres data on the presence and content of these elements were abstracted from treatment programmes and protocols. In a structured expert meeting consensus was reached on the presence of practice variation per element. Practice variation was observed in 22 of the 23 structure elements. The element "strategies for patient involvement" appeared similar in all rehabilitation centres, whereas differences were found in the elements regarding admission, exclusion and discharge criteria, patient subgroups, care pathways, team meetings, clinical assessments, maximum time to admission, aftercare and return to work modules, health professionals, treatment facilities, and care-giver involvement. Practice variation was found in a wide range of aspects of the structure of stroke rehabilitation.

A systematic methodology for selecting decontamination strategies following a biocontamination event.

PubMed

Krauter, Paula; Edwards, Donna; Yang, Lynn; Tucker, Mark

2011-09-01

Decontamination and recovery of a facility or outdoor area after a wide-area biological incident involving a highly persistent agent (eg, Bacillus anthracis spores) is a complex process that requires extensive information and significant resources, which are likely to be limited, particularly if multiple facilities or areas are affected. This article proposes a systematic methodology for evaluating information to select the decontamination or alternative treatments that optimize use of resources if decontamination is required for the facility or area. The methodology covers a wide range of approaches, including volumetric and surface decontamination, monitored natural attenuation, and seal and abandon strategies. A proposed trade-off analysis can help decision makers understand the relative appropriateness, efficacy, and labor, skill, and cost requirements of the various decontamination methods for the particular facility or area needing treatment--whether alone or as part of a larger decontamination effort. Because the state of decontamination knowledge and technology continues to evolve rapidly, the methodology presented here is designed to accommodate new strategies and materials and changing information.

In-depth assessment of an outbreak of Nipah encephalitis with person-to-person transmission in Bangladesh: implications for prevention and control strategies.

PubMed

Blum, Lauren S; Khan, Rasheda; Nahar, Nazmun; Breiman, Robert F

2009-01-01

Continued Nipah encephalitis outbreaks in Bangladesh highlight the need for preventative and control measures to reduce transmission from bats to humans and human-to-human spread. Qualitative research was conducted at the end of an encephalitis outbreak in Faridpur, Bangladesh in May 2004 and continued through December 2004. Methods included in-depth interviews with caretakers of cases, case survivors, neighbors of cases, and health providers. Results show contrasts between local and biomedical views on causal explanations and appropriate care. Social norms demanded that family members maintain physical contact with sick patients, potentially increasing the risk of human-to-human transmission. Initial treatment strategies by community members involved home remedies, and public health officials encouraged patient hospitalization. Over time, communities linked the outbreak to supernatural powers and sought care with spiritual healers. Differing popular and medical views of illness caused conflict and rejection of biomedical recommendations. Future investigators should consider local perceptions of disease and treatment when developing outbreak strategies.

[Adherence to pharmacological treatment in adult patients undergoing hemodialysis].

PubMed

Sgnaolin, Vanessa; Figueiredo, Ana Elizabeth Prado Lima

2012-06-01

Adherence to treatment in patients on hemodialysis is not a simple process. Strategies to promote adherence will meet the need for improvements in the process of orientation concerning the disease and its pharmacological treatment. To identify compliance with pharmacological treatment of patients on hemodialysis and the main factors related to it we used the Adherence Scale. Observational, descriptive and cross-sectional study. Interviews were conducted to collect socioeconomic, pharmacological data, as well as those regarding self-reported adherence to drug. Out of the 65 participants, 55.4% showed non-compliance. The mean number of drugs used was 4.1 ± 2.5 (self-report) and 6.2 ± 3.0 (prescription). Statistical analysis showed significant differences concerning compliance at different ages (> 60 years are more adherent). A significant proportion of patients have difficulty to comply with treatment and the main factor was forgetfulness. Regarding age, elderly patients are more adherent to treatment. The low level of knowledge about the used drugs may be one of the reasons for the lack of adherence, and the patient's orientation process by a team of multiprofessionals involved in assisting is a strategy to promote adherence.

Physiotherapy for functional motor disorders: a consensus recommendation

PubMed Central

Nielsen, Glenn; Stone, Jon; Matthews, Audrey; Brown, Melanie; Sparkes, Chris; Farmer, Ross; Masterton, Lindsay; Duncan, Linsey; Winters, Alisa; Daniell, Laura; Lumsden, Carrie; Carson, Alan; David, Anthony S; Edwards, Mark

2015-01-01

Background Patients with functional motor disorder (FMD) including weakness and paralysis are commonly referred to physiotherapists. There is growing evidence that physiotherapy is an effective treatment, but the existing literature has limited explanations of what physiotherapy should consist of and there are insufficient data to produce evidence-based guidelines. We aim to address this issue by presenting recommendations for physiotherapy treatment. Methods A meeting was held between physiotherapists, neurologists and neuropsychiatrists, all with extensive experience in treating FMD. A set of consensus recommendations were produced based on existing evidence and experience. Results We recommend that physiotherapy treatment is based on a biopsychosocial aetiological framework. Treatment should address illness beliefs, self-directed attention and abnormal habitual movement patterns through a process of education, movement retraining and self-management strategies within a positive and non-judgemental context. We provide specific examples of these strategies for different symptoms. Conclusions Physiotherapy has a key role in the multidisciplinary management of patients with FMD. There appear to be specific physiotherapy techniques which are useful in FMD and which are amenable to and require prospective evaluation. The processes involved in referral, treatment and discharge from physiotherapy should be considered carefully as a part of a treatment package. PMID:25433033

Improving Outcome of Psychosocial Treatments by Enhancing Memory and Learning

PubMed Central

Harvey, Allison G.; Lee, Jason; Williams, Joseph; Hollon, Steven D.; Walker, Matthew P.; Thompson, Monique A.; Smith, Rita

2014-01-01

Mental disorders are prevalent and lead to significant impairment. Progress toward establishing treatments has been good. However, effect sizes are small to moderate, gains may not persist, and many patients derive no benefit. Our goal is to highlight the potential for empirically-supported psychosocial treatments to be improved by incorporating insights from cognitive psychology and research on education. Our central question is: If it were possible to improve memory for content of sessions of psychosocial treatments, would outcome substantially improve? This question arises from five lines of evidence: (a) mental illness is often characterized by memory impairment, (b) memory impairment is modifiable, (c) psychosocial treatments often involve the activation of emotion, (d) emotion can bias memory and (e) memory for psychosocial treatment sessions is poor. Insights from scientific knowledge on learning and memory are leveraged to derive strategies for a transdiagnostic and transtreatment cognitive support intervention. These strategies can be applied within and between sessions and to interventions delivered via computer, the internet and text message. Additional novel pathways to improving memory include improving sleep, engaging in exercise and imagery. Given that memory processes change across the lifespan, services to children and older adults may benefit from cognitive support. PMID:25544856

Patient experiences of autonomy and coercion while receiving legal leverage in forensic assertive community treatment.

PubMed

Lamberti, J Steven; Russ, Ann; Cerulli, Catherine; Weisman, Robert L; Jacobowitz, David; Williams, Geoffrey C

2014-01-01

Legal leverage is broadly defined as the use of legal authority to promote treatment adherence. It is widely utilized within mental health courts, drug courts, mandated outpatient treatment programs, and other intervention strategies for individuals with mental illness or chemical dependency who have contact with the criminal justice system. Nonetheless, the ethics of using legal authority to promote treatment adherence remains a hotly debated issue within public and professional circles alike. While critics characterize legal leverage as a coercive form of social control that undermines personal autonomy, advocates contend that it supports autonomy because treatment strategies using legal leverage are designed to promote health and independence. Despite the controversy, there is little evidence regarding the impact of legal leverage on patient autonomy as experienced and expressed by patients themselves. This report presents findings from a qualitative study involving six focus groups with severely mentally ill outpatients who received legal leverage through three forensic assertive community treatment (FACT) programs in Northeastern, Midwestern, and West Coast cities. Findings are discussed in the context of the self-determination theory of human motivation, and practical implications for the use of legal leverage are considered.

Management and Treatment of Human Lice.

PubMed

Sangaré, Abdoul Karim; Doumbo, Ogobara K; Raoult, Didier

2016-01-01

Of the three lice (head, body, and pubic louse) that infest humans, the body louse is the species involved in epidemics of louse-borne typhus, trench fever, and relapsing fever, but all the three cause pediculosis. Their infestations occur today in many countries despite great efforts to maintain high standards of public health. In this review, literature searches were performed through PubMed, Medline, Google Scholar, and EBSCOhost, with key search words of "Pediculus humanus", "lice infestation", "pediculosis", and "treatment"; and controlled clinical trials were viewed with great interest. Removing lice by hand or with a lice comb, heating infested clothing, and shaving the scalp were some of the oldest methods of controlling human lice. Despite the introduction of other resources including cresol, naphthalene, sulfur, mercury, vinegar, petroleum, and insecticides, the numbers of lice infestation cases and resistance have increased. To date, viable alternative treatments to replace insecticides have been developed experimentally in vitro. Today, the development of new treatment strategies such as symbiotic treatment and synergistic treatment (antibiotics + ivermectin) in vitro has proved effective and is promising. Here, we present an overview on managing and treating human lice and highlight new strategies to more effectively fight pediculosis and prevent resistance.

Non-operative management of rectal cancer: understanding tumor biology.

PubMed

Wei, Iris H; Garcia-Aguilar, Julio

2018-05-24

The management of locally advanced rectal cancer involves a combination of chemotherapy, chemoradiation, and surgical resection to provide excellent local tumor control and overall survival. However, aspects of this multimodality approach are associated with significant morbidity and longterm sequelae. In addition, there is growing evidence that patients with a clinical complete response to chemotherapy and chemoradiation treatments may be safely offered initial non-operative management in a rigorous surveillance program. Developing effective methods, such as molecular biomarkers, to predict a patient's response to therapies are therefore needed to help guide personalized treatment strategies. The treatment of locally advanced rectal cancer focuses on a multimodality approach of systemic chemotherapy, radiation, and total mesorectal excision to maximize oncologic outcomes. While combined modality treatment for LARC results in excellent local tumor control and patient survival, the treatments are associated with significant morbidity and long-term functional complications that can impair quality of life. In addition, the tumor response to neoadjuvant therapy is quite variable.2 Weighed against the morbidity and significant sequelae of rectal resection, recognizing how to best optimize nonoperative strategies without compromising oncologic outcomes is critical to our understanding and treatment of this disease.

New outlook on the diagnosis, treatment and follow-up of childhood-onset craniopharyngioma.

PubMed

Müller, Hermann L; Merchant, Thomas E; Puget, Stephanie; Martinez-Barbera, Juan-Pedro

2017-05-01

Childhood-onset craniopharyngiomas are rare embryonic tumours of low-grade histological malignancy. Novel insights into the molecular pathogenesis of human adamantinomatous craniopharyngioma have started to unveil the possibility of testing novel treatments targeting pathogenic pathways. Hypothalamic involvement and/or treatment-related lesions result in impaired physical and social functionality and in severe neuroendocrine sequelae. Quality of survival in patients with craniopharyngioma with hypothalamic involvement is impaired by severe obesity, physical fatigue and non-optimal psychosocial development. Patients with craniopharyngioma involving hypothalamic structures have reduced 20-year overall survival, but overall and progression-free survival are not related to the degree of surgical resection. Irradiation is effective in the prevention of tumour progression and recurrence. For favourably localized craniopharyngiomas, the preferred treatment of choice is to attempt complete resection with preservation of visual, hypothalamic and pituitary function. For unfavourably localized tumours in close proximity to optic and/or hypothalamic structures, a radical neurosurgical strategy attempting complete resection is not recommended owing to potential severe sequelae. As expertise has been shown to have an impact on post-treatment morbidity, medical societies should establish criteria for adequate professional expertise for the treatment of craniopharyngioma. On the basis of these criteria, health authorities should organize the certification of centres of excellence that are authorized to treat and care for patients with this chronic disease.

A Systematic Review of Relaxation, Meditation, and Guided Imagery Strategies for Symptom Management in Heart Failure.

PubMed

Kwekkeboom, Kristine L; Bratzke, Lisa C

2016-01-01

Pain, dyspnea, fatigue, and sleep disturbance are prevalent and distressing symptoms in persons with advanced heart failure. Although many lifestyle and self-care interventions have been developed to control heart failure progression, very few studies have explored treatments exclusively for symptom palliation. Cognitive-behavioral strategies may be effective treatment for these symptoms in advanced heart failure. A systemic review was conducted to describe the effect of cognitive-behavioral strategies on pain, dyspnea, fatigue, and sleep disturbance in patients with heart failure. CINAHL, Medline, and PsychINFO were searched from inception through December 2014. Articles were selected for inclusion if they tested a cognitive-behavioral strategy using a quasi-experimental or experimental design, involved a sample of adults with heart failure, and measured pain, dyspnea, fatigue, sleep disturbance, or symptom-related quality of life. The 2 authors evaluated study quality, abstracted data elements from each study, and synthesized findings. Thirteen articles describing 9 unique studies met criteria and were included in the review. Five studies tested relaxation strategies, 3 tested meditation strategies, and 1 tested a guided imagery strategy. Of the 9 studies, 7 demonstrated some improvement in symptom outcomes. Relaxation, meditation, guided imagery, or combinations of these strategies resulted in less dyspnea and better sleep compared with attention control or usual care conditions and reduced pain, dyspnea, fatigue, and sleep disturbance within treatment groups (pretreatment to posttreatment). Symptom-related quality of life was improved with meditation compared with attention control and usual care conditions and improved pre- to post-guided imagery. Studies exploring cognitive-behavioral symptom management strategies in heart failure vary in quality and report mixed findings but indicate potential beneficial effects of relaxation, meditation, and guided imagery on heart failure-related symptoms. Future research should test cognitive-behavioral strategies in rigorously designed efficacy trials, using samples selected for their symptom experience, and measure pain, dyspnea, fatigue, and sleep disturbance outcomes with targeted symptom measures.

Helpful self-management strategies to cope with enduring depression from the patients' point of view: a concept map study.

PubMed

van Grieken, Rosa A; Kirkenier, Anneloes C E; Koeter, Maarten W J; Schene, Aart H

2014-12-13

Despite the development of various self-management programmes that attempt to ameliorate symptoms of patients with chronic major depressive disorder (MDD), little is known about what these patients perceive as helpful in their struggle during daily live. The present study aims to explore what patients believe they can do themselves to cope with enduring MDD besides professional treatment, and which self-management strategies patients perceive as being most helpful to cope with their MDD. We used concept mapping, a method specifically designed for the conceptualisation of a specific subject, in this case patients' point of view (n = 25) on helpful self-management strategies in their coping with enduring MDD. A purposive sample of participants was invited at the Academic Medical Center and through requests on several MDD-patient websites in the Netherlands. Participants generated strategies in focus group discussions which were successively clustered on a two-dimensional concept map by hierarchical cluster analysis. Fifty strategies were perceived as helpful. They were combined into three meta-clusters each comprising two clusters: A focus on the depression (sub clusters: Being aware that my depression needs active coping and Active coping with professional treatment); An active lifestyle (sub clusters: Active self-care, structure and planning and Free time activities) and Participation in everyday social life (sub clusters: Social engagement and Work-related activities). MDD patients believe they can use various strategies to cope with enduring MDD in daily life. Although current developments in e-health occur, patients emphasise on face-to-face treatments and long-term relations, being engaged in social and working life, and involving their family, friends, colleagues and clinicians in their disease management. Our findings may help clinicians to improve their knowledge about what patients consider beneficial to cope with enduring MDD and to incorporate these suggested self-management strategies in their treatments.

The Childhood Arthritis and Rheumatology Research Alliance Consensus Treatment Plans: Toward Comparative Effectiveness in the Pediatric Rheumatic Diseases.

PubMed

Ringold, Sarah; Nigrovic, Peter A; Feldman, Brian M; Tomlinson, George A; von Scheven, Emily; Wallace, Carol A; Huber, Adam M; Schanberg, Laura E; Li, Suzanne C; Weiss, Pamela F; Fuhlbrigge, Robert C; Morgan, Esi M; Kimura, Yukiko

2018-05-01

The pediatric rheumatic diseases are a heterogeneous group of rare diseases, posing a number of challenges for the use of traditional clinical and translational research methods. Innovative comparative effectiveness approaches are needed to efficiently study treatment strategies and disease outcomes. The Childhood Arthritis and Rheumatology Research Alliance (CARRA) developed the consensus treatment plan (CTP) approach as a comparative effectiveness tool for research in pediatric rheumatology. CTPs are treatment strategies, developed by consensus methods among CARRA members, intended to reduce variation in treatment approaches, standardize outcome measurements, and allow for comparison of the effectiveness of different approaches with the goal of improving disease outcomes. To date, CTPs have been published for 8 different diseases and disease manifestations. The approach has been successfully piloted for juvenile localized scleroderma, systemic juvenile idiopathic arthritis (JIA), polyarticular JIA, dermatomyositis, and lupus nephritis. Large-scale studies are underway for systemic JIA and polyarticular JIA, with the CARRA patient registry serving as the data collection platform. These studies have been designed with stakeholder involvement, including active input from CARRA providers, patients, and parents, with the goal of increasing feasibility and ensuring the relevance of the outcomes. These studies include ancillary biologic specimen collection intended to support additional translational and mechanistic studies. Data from these ongoing CTP studies will provide more information on the ability of this approach to identify effective treatment strategies and improve outcomes in the pediatric rheumatic diseases. © 2018, American College of Rheumatology.

The Art and Skill of Delivering Culturally Responsive TF-CBT in Tanzania and Kenya

PubMed Central

Kava, Christine M.; Akiba, Christopher F.; Lucid, Leah; Dorsey, Shannon

2016-01-01

Objective This study explored the facilitators, barriers, and strategies used to deliver a child mental health evidence-based treatment (EBT), trauma-focused cognitive behavioral therapy (TF-CBT), in a culturally responsive manner. In low- and middle-income countries most individuals with mental health problems do not receive treatment due to a shortage of mental health professionals. One approach to addressing this problem is task-sharing, in which lay counselors are trained to deliver mental health treatment. Combining this approach with a focus on EBT provides a strategy for bridging the mental health treatment gap. However, little is known how about western-developed EBTs are delivered in a culturally responsive manner. Method Semistructured qualitative interviews were conducted with 12 TF-CBT lay counselors involved in a large randomized controlled trial of TF-CBT in Kenya and Tanzania. An inductive approach was used to analyze the data. Results Lay counselors described the importance of being responsive to TF-CBT participants’ customs, beliefs, and socioeconomic conditions and highlighted the value of TF-CBT for their community. They also discussed the importance of partnering with other organizations to address unmet socioeconomic needs. Conclusion The findings from this study provide support for the acceptability and appropriateness of TF-CBT as a treatment approach for improving child mental health. Having a better understanding of the strategies used by lay counselors to ensure that treatment is relevant to the cultural and socioeconomic context of participants can help to inform the implementation of future EBTs. PMID:27414470

Avoidant coping moderates the relationship between paternal involvement in the child's type 1 diabetes (T1D) care and parenting stress.

PubMed

Teasdale, Ashley; Limbers, Christine

2018-01-01

Fathers may experience greater parenting stress and anxiety when they are more involved in their child's type 1 diabetes (T1D) care. The present study evaluated whether seeking social support and avoidant coping strategies moderate the relationship between paternal involvement in the child's T1D care and parenting stress in an international sample. Two hundred forty-nine fathers of young children with T1D completed the Parenting Stress Index (PSI), Pediatric Inventory for Parents (PIP), Dads' Active Disease Support scale (DADS), COPE Inventory, Self-Care Inventory (SCI-R), and a demographic questionnaire online. Pearson's product moment correlations were computed, and multiple linear regression analysis was conducted with three separate models in which the PSI Child Domain, PIP Frequency, and PIP Difficulty scores represented different parenting stress outcomes. The interaction between use of denial coping and DADS Involvement was significantly correlated with general parenting stress ( p < .05). There were no significant interactions between instrumental social support and DADS Involvement; however, use of instrumental social support coping was significantly correlated with difficulty of pediatric parenting stress ( p < .05), DADS Involvement ( p < .001), and SCI-R better adherence to the child diabetes treatment regimen ( p < .001). Avoidant coping strategies are associated with more general parenting stress, especially when fathers are more involved in T1D management.

Treating Drug Abuse and Addiction in the Criminal Justice System: Improving Public Health and Safety

PubMed Central

Chandler, Redonna K.; Fletcher, Bennett W.; Volkow, Nora D.

2009-01-01

Despite increasing evidence that addiction is a treatable disease of the brain, most individuals do not receive treatment. Involvement in the criminal justice system often results from illegal drug-seeking behavior and participation in illegal activities that reflect, in part, disrupted behavior ensuing from brain changes triggered by repeated drug use. Treating drug-involved offenders provides a unique opportunity to decrease substance abuse and reduce associated criminal behavior. Emerging neuroscience has the potential to transform traditional sanction-oriented public safety approaches by providing new therapeutic strategies against addiction that could be used in the criminal justice system. We summarize relevant neuroscientific findings and evidence-based principles of addiction treatment that, if implemented in the criminal justice system, could help improve public heath and reduce criminal behavior. PMID:19141766

Positioning the principles of precision medicine in care pathways for allergic rhinitis and chronic rhinosinusitis - A EUFOREA-ARIA-EPOS-AIRWAYS ICP statement.

PubMed

Hellings, P W; Fokkens, W J; Bachert, C; Akdis, C A; Bieber, T; Agache, I; Bernal-Sprekelsen, M; Canonica, G W; Gevaert, P; Joos, G; Lund, V; Muraro, A; Onerci, M; Zuberbier, T; Pugin, B; Seys, S F; Bousquet, J

2017-09-01

Precision medicine (PM) is increasingly recognized as the way forward for optimizing patient care. Introduced in the field of oncology, it is now considered of major interest in other medical domains like allergy and chronic airway diseases, which face an urgent need to improve the level of disease control, enhance patient satisfaction and increase effectiveness of preventive interventions. The combination of personalized care, prediction of treatment success, prevention of disease and patient participation in the elaboration of the treatment plan is expected to substantially improve the therapeutic approach for individuals suffering from chronic disabling conditions. Given the emerging data on the impact of patient stratification on treatment outcomes, European and American regulatory bodies support the principles of PM and its potential advantage over current treatment strategies. The aim of the current document was to propose a consensus on the position and gradual implementation of the principles of PM within existing adult treatment algorithms for allergic rhinitis (AR) and chronic rhinosinusitis (CRS). At the time of diagnosis, prediction of success of the initiated treatment and patient participation in the decision of the treatment plan can be implemented. The second-level approach ideally involves strategies to prevent progression of disease, in addition to prediction of success of therapy, and patient participation in the long-term therapeutic strategy. Endotype-driven treatment is part of a personalized approach and should be positioned at the tertiary level of care, given the efforts needed for its implementation and the high cost of molecular diagnosis and biological treatment. © 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

Model-Based Therapeutic Correction of Hypothalamic-Pituitary-Adrenal Axis Dysfunction

PubMed Central

Ben-Zvi, Amos; Vernon, Suzanne D.; Broderick, Gordon

2009-01-01

The hypothalamic-pituitary-adrenal (HPA) axis is a major system maintaining body homeostasis by regulating the neuroendocrine and sympathetic nervous systems as well modulating immune function. Recent work has shown that the complex dynamics of this system accommodate several stable steady states, one of which corresponds to the hypocortisol state observed in patients with chronic fatigue syndrome (CFS). At present these dynamics are not formally considered in the development of treatment strategies. Here we use model-based predictive control (MPC) methodology to estimate robust treatment courses for displacing the HPA axis from an abnormal hypocortisol steady state back to a healthy cortisol level. This approach was applied to a recent model of HPA axis dynamics incorporating glucocorticoid receptor kinetics. A candidate treatment that displays robust properties in the face of significant biological variability and measurement uncertainty requires that cortisol be further suppressed for a short period until adrenocorticotropic hormone levels exceed 30% of baseline. Treatment may then be discontinued, and the HPA axis will naturally progress to a stable attractor defined by normal hormone levels. Suppression of biologically available cortisol may be achieved through the use of binding proteins such as CBG and certain metabolizing enzymes, thus offering possible avenues for deployment in a clinical setting. Treatment strategies can therefore be designed that maximally exploit system dynamics to provide a robust response to treatment and ensure a positive outcome over a wide range of conditions. Perhaps most importantly, a treatment course involving further reduction in cortisol, even transient, is quite counterintuitive and challenges the conventional strategy of supplementing cortisol levels, an approach based on steady-state reasoning. PMID:19165314

The Use of High-Frequency Percussive Ventilation for Whole-Lung Lavage: A Case Report.

PubMed

Kinthala, Sudhakar; Liang, Mark; Khusid, Felix; Harrison, Sebron

2018-04-23

Whole-lung lavage (WLL) remains the gold standard in the treatment of pulmonary alveolar proteinosis. However, anesthetic management during WLL can be challenging because of the risk of intraoperative hypoxemia and various cardiorespiratory complications of 1-lung ventilation. Here, we describe a novel strategy involving the application of high-frequency percussive ventilation using a volumetric diffusive respirator (VDR-4) during WLL in a 47-year-old woman with pulmonary alveolar proteinosis. Our observations suggest that high-frequency percussive ventilation is a potentially effective ventilation strategy during WLL that may reduce the risk of hypoxemia and facilitate lavage.

Obliteration of a giant fusiform carotid terminus-M1 aneurysm after distal clip application and extracranial-intracranial bypass. Case report.

PubMed

Ferroli, P; Ciceri, E; Parati, E; Minati, L; Broggi, G

2007-06-01

Giant intracranial aneurysms may not be amenable to direct surgical clipping or endovascular coiling because of three critical factors: 1) lack of clear aneurysmal neck; 2) giant size; 3) involvement with critical perforating or branch vessels. Techniques of flow redirection, however, may offer an alternative treatment strategy for these difficult lesions. In this paper, we report on the use of this alternative strategy in the successful treatment of a left giant fusiform carotid terminus-M1 aneurysm in a 16 year-old boy suffering from Ehler-Danlos disease. This patient was admitted to our Institution because his aneurysm was continuing to be increasing in size, despite a previous ligation of his left cervical ICA which was performed at another institution 2 years earlier after the patient had experienced a hemorrhagic stroke. Upon admission, a neurological examination revealed a slight motor aphasia with mild right hemiparesis, remnant of the ancient stroke. Because of its size and the involvement with M1 perforating arteries, a direct aneurysm attack was deemed inadvisable. After an initial ECA-ICA high flow bypass which spontaneously thrombosed, we performed a repeated high flow bypass with the application of a single clip on M1, right distal to the fusiform dilatation. After an uneventful postoperative course, we were unable to observe any new neurological deficits after surgery. A CT scan on postoperative day 1 revealed that the aneurysm had undergone a spontaneous thrombosis which was completely obliterated at the time of a 6-month follow-up angiogram. At that time, the ECA-ICA bypass was found to be patent. In conclusion the alternative of flow alteration strategies can be successfully used in the treatment of aneurysms that cannot be safely trapped or occluded by traditional neurosurgical methods.

Robust Membranes for Sustainable Wastewater Treatment by Forward Osmosis in FOBs

DTIC Science & Technology

2017-05-09

the Department of Defense Strategic Environmental Research and Development Program (SERDP). The publication of this report does not indicate...CT 06511 9. SPONSORING / MONITORING AGENCY NAME(S) AND ADDRESS(ES) 10. SPONSOR/MONITOR’S ACRONYM(S) Strategic Environmental Research and...strategies, in-situ fabrication and post -fabrication membrane modification. In-situ fabrication modification involves fabrication of a polyamide selective

Monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM): novel biological insights and development of early treatment strategies

PubMed Central

Kristinsson, Sigurdur Y.

2011-01-01

Monoclonal gammopathy of unknown significance (MGUS) and smoldering multiple myeloma (SMM) are asymptomatic plasma cell dyscrasias, with a propensity to progress to symptomatic MM. In recent years there have been improvements in risk stratification models (involving molecular markers) of both disorders, which have led to better understanding of the biology and probability of progression of MGUS and SMM. In the context of numerous molecular events and heterogeneous risk of progression, developing individualized risk profiles for patients with MGUS and SMM represents an ongoing challenge that has to be addressed by prospective clinical monitoring and extensive correlative science. In this review we discuss the current standard of care of patients with MGUS and SMM, the use of risk models, including flow cytometry and free-light chain analyses, for predicting risk of progression. Emerging evidence from molecular studies on MGUS and SMM, involving cytogenetics, gene-expression profiling, and microRNA as well as molecular imaging is described. Finally, future directions for improving individualized management of MGUS and SMM patients, as well as the potential for developing early treatment strategies designed to delay and prevent development of MM are discussed. PMID:21441462

Monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM): novel biological insights and development of early treatment strategies.

PubMed

Korde, Neha; Kristinsson, Sigurdur Y; Landgren, Ola

2011-05-26

Monoclonal gammopathy of unknown significance (MGUS) and smoldering multiple myeloma (SMM) are asymptomatic plasma cell dyscrasias, with a propensity to progress to symptomatic MM. In recent years there have been improvements in risk stratification models (involving molecular markers) of both disorders, which have led to better understanding of the biology and probability of progression of MGUS and SMM. In the context of numerous molecular events and heterogeneous risk of progression, developing individualized risk profiles for patients with MGUS and SMM represents an ongoing challenge that has to be addressed by prospective clinical monitoring and extensive correlative science. In this review we discuss the current standard of care of patients with MGUS and SMM, the use of risk models, including flow cytometry and free-light chain analyses, for predicting risk of progression. Emerging evidence from molecular studies on MGUS and SMM, involving cytogenetics, gene-expression profiling, and microRNA as well as molecular imaging is described. Finally, future directions for improving individualized management of MGUS and SMM patients, as well as the potential for developing early treatment strategies designed to delay and prevent development of MM are discussed.

Challenges and open issues in the management of acquired hemophilia A (AHA).

PubMed

Shetty, Shrimati D; Ghosh, Kanjaksha

2015-03-01

Acquired hemophilia A (AHA) is a rare autoimmune bleeding disorder caused by antibodies which neutralize the function of factor VIII (FVIII). The disease presents a complex clinical challenge to the treating Physicians and Hematologists. As the disease is associated with high mortality, prompt management is necessary. Early recognition, quick diagnosis and timely referral to a specialized center are important for better management of these patients. The different clinical manifestations, underlying pathology, inhibitor kinetics and the associated age related comorbidities do not allow extrapolation of the treatment protocols of congenital hemophilia to AHA. The basic strategies of the management of AHA patients involve maintaining hemostasis, suppression or eradication of antibodies, diagnosis and treatment of underlying pathology and avoid treatment related complications like thrombosis. The efficiency of hemostatic agents which are generally used to treat AHA is unpredictable. Due to the rarity of the disease, there are no randomized clinical trials on the management of this disorder and thus the expertise and experience of the treating Physicians' guide treatment strategies. Copyright © 2014 Elsevier Inc. All rights reserved.

The pharmacotherapy of chronic pain: A review

PubMed Central

Lynch, Mary E; Watson, C Peter N

2006-01-01

The past two decades have contributed a large body of preclinical work that has assisted in our understanding of the underlying pathophysiological mechanisms that cause chronic pain. In this context, it has been recognized that effective treatment of pain is a priority and that treatment often involves the use of one or a combination of agents with analgesic action. The current review presents an evidence-based approach to the pharmacotherapy of chronic pain. Medline searches were done for all agents used as conventional treatment in chronic pain. Published papers up to June 2005 were included. The search strategy included randomized, controlled trials, and where available, systematic reviews and meta-analyses. Further references were found in reference sections of papers located using the above search strategy. Agents for which there were no controlled trials supporting efficacy in treatment of chronic pain were not included in the present review, except in cases where preclinical science was compelling, or where initial human work has been positive and where it was thought the reader would be interested in the scientific evidence to date. PMID:16511612

Treatment of Advanced Malignant Uterine Perivascular Epithelioid Cell Tumor with mTOR Inhibitors: Single-institution Experience and Review of the Literature.

PubMed

Starbuck, Kristen D; Drake, Richard D; Budd, G Thomas; Rose, Peter G

2016-11-01

Uterine perivascular epithelioid cell tumors (PEComas) are rare mesenchymal tumors. Many have malignant behavior, and no successful treatment strategy has been established. Identification of mutations in the tuberous sclerosis 1 (TSC1) and TSC2 genes producing constitutive activation of the mammalian target of rapamycin (mTOR) pathway presents an opportunity for targeted therapy. Patients with advanced malignant uterine PEComa treated with mTOR inhibitors were identified and records were retrospectively reviewed for treatment response based on radiographic assessment. Three patients with advanced uterine PEComas underwent debulking surgery followed by mTOR inhibitor therapy; two had a complete response to therapy and disease in one patient progressed. Given the absence of effective therapies for malignant uterine PEComas, targeting the mTOR pathway is a logical strategy to pursue given the known pathobiology involving the Tuberous Sclerosis complex. Treatment of malignant uterine PEComas with mTOR inhibitors was effective in two out of three patients after surgical resection, with durable response. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Nodular pulmonary amyloidosis with primary pulmonary MALT lymphoma masquerading as metastatic lung disease

PubMed Central

Upadhaya, Sunil; Baig, Mohd; Towfiq, Basim; Al Hadidi, Samer

2017-01-01

ABSTRACT Nodular pulmonary amyloidosis is a very rare form of localized amyloidosis involving the lung, with very little known about its nature. It is usually associated with indolent B cell lymphoproliferative disorder and also connective tissue disorders. No definite treatment guideline exists. Many patients respond to chemotherapy with low risk of progression and a ‘wait and watch’ strategy is also considered a valid treatment option. In this report the authors present a case of nodular pulmonary amyloidosis with pulmonary mucosa associated lymphoid tissue (MALT) lymphoma that presented with features of metastatic malignant disease and after definitive diagnosis decided not to undergo treatment. PMID:28808514

Anticancer Activity of Curcumin and Its Analogues: Preclinical and Clinical Studies.

PubMed

Allegra, Alessandro; Innao, Vanessa; Russo, Sabina; Gerace, Demetrio; Alonci, Andrea; Musolino, Caterina

2017-01-02

Curcumin has been shown to have a wide variety of therapeutic effects, ranging from anti-inflammatory, chemopreventive, anti-proliferative, and anti-metastatic. This review provides an overview of the recent research conducted to overcome the problems with the bioavailability of curcumin, and of the preclinical and clinical studies that have reported success in combinatorial strategies coupling curcumin with other treatments. Research on the signaling pathways that curcumin treatment targets shows that it potently acts on major intracellular components involved in key processes such as genomic modulations, cell invasion and cell death pathways. Curcumin is a promising molecule for the prevention and treatment of cancer.

Bacteriocins – Exploring Alternatives to Antibiotics in Mastitis Treatment

PubMed Central

Pieterse, Reneé; Todorov, Svetoslav D.

2010-01-01

Mastitis is considered to be the most costly disease affecting the dairy industry. Management strategies involve the extensive use of antibiotics to treat and prevent this disease. Prophylactic dosages of antibiotics used in mastitis control programmes could select for strains with resistance to antibiotics. In addition, a strong drive towards reducing antibiotic residues in animal food products has lead to research in finding alternative antimicrobial agents. In this review we have focus on the pathogenesis of the mastitis in dairy cows, existing antibiotic treatments and possible alternative for application of bacteriocins from lactic acid bacteria in the treatment and prevention of this disease. PMID:24031528

Toward a Biology-Driven Treatment Strategy for Peripheral T-cell Lymphoma

PubMed Central

Hildyard, CAT; Shiekh, S; Browning, JAB; Collins, GP

2017-01-01

T-cell and natural killer–cell lymphomas are a relatively rare and heterogeneous group of diseases that are difficult to treat and usually have poor outcomes. To date, therapeutic interventions are of limited efficacy and there is a pressing need to find better treatments. In recent years, advances in molecular biology have helped to elucidate the underlying genetic complexity of this group of diseases and to identify mutations and signaling pathways involved in lymphomagenesis. In this review, we highlight the unique biological characteristics of some of the different subtypes and discuss how these may be targeted to provide more individualized and effective treatment approaches. PMID:28579857

Strategies to minimize cognitive side effects with ECT: aspects of ECT technique.

PubMed

Prudic, Joan

2008-03-01

The adverse cognitive effects of electroconvulsive therapy are important limitations in the use of this treatment that continues to be a significant therapeutic strategy after 7 decades of use. Among the approaches to mitigation of these side effects are considerations involving the prescription and manipulation of the electrical stimulus itself. The impact of the following electrical factors on the cognitive outcomes of electroconvulsive therapy are surveyed: efficiency of the stimulus as expressed in electrical waveform; targeting of the stimulus, the major concept underlying electrode placement; stimulus dosing; and frequency and number of treatments. The current state of development of knowledge in these areas is summarized, and methods to achieve the best cognitive outcomes without sacrificing clinical efficacy are discussed. Future trends in the further optimization of the electrical stimulus are briefly mentioned.

Drugs currently under investigation for the treatment of invasive candidiasis.

PubMed

McCarthy, Matthew W; Walsh, Thomas J

2017-07-01

The widespread implementation of immunosuppressants, immunomodulators, hematopoietic stem cell transplantation and solid organ transplantation in clinical practice has led to an expanding population of patients who are at risk for invasive candidiasis, which is the most common form of fungal disease among hospitalized patients in the developed world. The emergence of drug-resistant Candida spp. has added to the morbidity associated with invasive candidiasis and novel therapeutic strategies are urgently needed. Areas covered: In this paper, we explore investigational agents for the treatment of invasive candidiasis, with particular attention paid to compounds that have recently entered phase I or phase II clinical trials. Expert opinion: The antifungal drug development pipeline has been severely limited due to regulatory hurdles and a systemic lack of investment in novel compounds. However, several promising drug development strategies have recently emerged, including chemical screens involving Pathogen Box compounds, combination antifungal therapy, and repurposing of existing agents that were initially developed to treat other conditions, all of which have the potential to redefine the treatment of invasive candidiasis.

Apple orchard pest control strategies affect bird communities in southeastern France.

PubMed

Bouvier, Jean-Charles; Ricci, Benoît; Agerberg, Julia; Lavigne, Claire

2011-01-01

Birds are regarded as appropriate biological indicators of how changes in agricultural practices affect the environment. They are also involved in the biocontrol of pests. In the present study, we provide an assessment of the impact of pest control strategies on bird communities in apple orchards in southeastern France. We compared the structure (abundance, species richness, and diversity) of breeding bird communities in 15 orchards under conventional or organic pest control over a three-year period (2003-2005). Pest control strategies and their evolution over time were characterized by analyzing farmers' treatment schedules. The landscape surrounding the orchards was characterized using a Geographic Information System. We observed 30 bird species overall. Bird abundance, species richness, and diversity were all affected by pest control strategies, and were highest in organic orchards and lowest in conventional orchards during the three study years. The pest control strategy affected insectivores more than granivores. We further observed a tendency for bird communities in integrated pest management orchards to change over time and become increasingly different from communities in organic orchards, which also corresponded to changes in treatment schedules. These findings indicate that within-orchard bird communities may respond quickly to changes in pesticide use and may, in turn, influence biocontrol of pests by birds. © 2010 SETAC.

Can Australia eliminate TB? Modelling immigration strategies for reaching MDG targets in a low-transmission setting.

PubMed

Denholm, Justin T; McBryde, Emma S

2014-02-01

The 2050 Millennium Development Goals (MDG) for tuberculosis (TB) aim for elimination of TB as a public health issue. We used a mathematical modelling approach to evaluate the feasibility of this target in a low-prevalence setting with immigration-related strategies directed at latent tuberculosis. We used a stochastic individual-based model to simulate tuberculosis disease among immigrants to Victoria, Australia; a representative low-transmission setting. A variety of screening and treatment approaches aimed at preventing reactivation of latent infection were applied to evaluate overall tuberculosis incidence reduction and rates of multidrug resistant disease. Without additional intervention, tuberculosis incidence was predicted to reach 34.5 cases/million by 2050. Strategies involving the introduction of an available screening/treatment combination reduced TB incidence to between 16.9-23.8 cases/million, and required screening of 136-427 new arrivals for each case of TB prevented. Limiting screening to higher incidence regions of origin was less effective but more efficient. Public health strategies targeting latent tuberculosis infection in immigrants may substantially reduce tuberculosis incidence in a low prevalence region. However, immigration-focused strategies cannot achieve the 2050 MDG and alternative or complementary approaches are required. © 2014 The Authors. ANZJPH © 2014 Public Health Association of Australia.

Individualisation of drug treatments for patients with long-term conditions: a review of concepts

PubMed Central

Denford, S; Frost, J; Dieppe, P; Cooper, Chris; Britten, N

2014-01-01

Objectives Patients and policy makers advocate that drug treatments should be individualised. However, the term is used in a variety of ways. We set out to identify the range of related terminology and concepts in the general field of individualisation, map out the relationships between these concepts and explore how patients’ perspectives are considered. Design We consulted members of an established patient and public involvement group about their experience of medicine taking for long-term conditions and their ideas about individualisation. We then conducted a scoping review of the literature to explore how terms surrounding individualisation of drug treatment are used and defined in the literature, and to explore the extent to which patients’ perspectives are represented, with a view to informing future recommendations as to how individualisation can be operationalised. Methods We identified relevant literature using a range of search strategies. Two researchers independently extracted definitions of terms using a template. Inductive and deductive methods were used to explore the data. Results Definitions were categorised according to the following themes: medical management; pharmacogenetics, the patient's perspective; interactions between the healthcare provider and patient and management of long-term conditions. Conclusions Within the literature reviewed, the involvement of patients in the ongoing management of drug treatment was largely absent. We propose the use of a new term ‘mutually agreed tailoring’ (MAT). This describes the ongoing pharmacological management of conditions that incorporates patients’ specific needs, experiences and existing strategies for using their medications, and the professionals’ clinical judgement. This usually includes patients monitoring their symptoms and, with the support of the professional, making appropriate product, dose or timing adjustments as necessary. Our previous work suggests that many patients and doctors are successfully practising MAT, so we suggest that a formal description may facilitate wider utilisation of strategies that will improve patient outcomes. PMID:24670429

Oncological strategies for locally advanced rectal cancer with synchronous liver metastases, interval strategy versus rectum first strategy: a comparison of short-term outcomes.

PubMed

Salvador-Rosés, H; López-Ben, S; Casellas-Robert, M; Planellas, P; Gómez-Romeu, N; Farrés, R; Ramos, E; Codina-Cazador, A; Figueras, J

2017-12-22

The goal of treatment for patients with synchronous liver metastases (SLM) from rectal cancer is to achieve a complete resection of both tumor locations. For patients with symptomatic locally advanced rectal cancer with resectable SLM at diagnosis, our usual strategy has been the rectum first approach (RF). However, since 2014, we advocate for the interval approach (IS) that involves the administration of chemo-radiotherapy followed by the resection of the SLM in the interval of time between rectal cancer radiation and rectal surgery. From 2010 to 2016, 16 patients were treated according to this new strategy and 19 were treated according RF strategy. Data were collected prospectively and analyzed with an intention-to-treat perspective. Complete resection rate, duration of the treatment and morbi-mortality were the main outcomes. The complete resection rate in the IS was higher (100%, n = 16) compared to the RF (74%, n = 14, p = 0.049) and the duration of the strategy was shorter (6 vs. 9 months, respectively, p = 0.006). The incidence of severe complications after liver surgery was 14% (n = 2) in the RF and 0% in the IS (p = 1.000), and after rectal surgery was 24% (n = 4) and 12% (n = 2), respectively (p = 1.000). The IS is a feasible and safe strategy that procures higher level of complete resection rate in a shorter period of time compared to RF strategy.

Multidisciplinary Consensus on the Nonadherence to Clinical Management of Inhaled Therapy in Spanish asthma patients.

PubMed

López-Viña, Antolín; Giner, Jordi; Molina, Jesús; Palicio, Javier; Plaza, Javier; Quintano, José Antonio; Quirce, Santiago; Soria, Cristina; Uréndez, Ana María; Plaza, Vicente

2017-08-01

Rates of nonadherence to asthma treatment in Spain are between 24% and 76%, which results in poor disease control and increased health care costs. The main objective of this multidisciplinary consensus was to investigate the opinions of health professionals and patients regarding adherence to inhaled therapy in Spain. The results will help to identify the causes of nonadherence and to establish strategies to detect and correct the problem. This research was conducted by using a modified Delphi method organized into 2 rounds and involving a panel of 64 physicians, 16 nurses, and 10 community pharmacists. In addition, 70 patients with asthma completed a simplified 1-round survey, based on the Delphi questionnaire. The items proposed to reach a consensus included topics such as impact and causes of nonadherence, as well as strategies to improve adherence to treatment. Expert panelists reached a consensus on ~80% of the items proposed. They agreed that the lack of control in asthma has an important economic impact. The causes of nonadherence with more agreement were the patients' beliefs about treatment and the complexity of the inhalation devices. Panelists agreed that the most important strategies to improve adherence were modification of patients' beliefs, training of professionals in the management of adherence, and personalization of interventions. Most patients only agreed with items that referred to strategies to improve adherence. Although the problems, impact, causes, and interventions regarding nonadherence to asthma treatment are known, adequate monitoring of adherence to treatment is not performed. A multidisciplinary and personalized approach is necessary to control and improve adherence. Copyright © 2017 Elsevier HS Journals, Inc. All rights reserved.

Pressure ulcers: implementation of evidence-based nursing practice.

PubMed

Clarke, Heather F; Bradley, Chris; Whytock, Sandra; Handfield, Shannon; van der Wal, Rena; Gundry, Sharon

2005-03-01

A 2-year project was carried out to evaluate the use of multi-component, computer-assisted strategies for implementing clinical practice guidelines. This paper describes the implementation of the project and lessons learned. The evaluation and outcomes of implementing clinical practice guidelines to prevent and treat pressure ulcers will be reported in a separate paper. The prevalence and incidence rates of pressure ulcers, coupled with the cost of treatment, constitute a substantial burden for our health care system. It is estimated that treating a pressure ulcer can increase nursing time up to 50%, and that treatment costs per ulcer can range from US$10,000 to $86,000, with median costs of $27,000. Although evidence-based guidelines for prevention and optimum treatment of pressure ulcers have been developed, there is little empirical evidence about the effectiveness of implementation strategies. The study was conducted across the continuum of care (primary, secondary and tertiary) in a Canadian urban Health Region involving seven health care organizations (acute, home and extended care). Trained surveyors (Registered Nurses) determined the prevalence and incidence of pressure ulcers among patients in these organizations. The use of a computerized decision-support system assisted staff to select optimal, evidence-based care strategies, record information and analyse individual and aggregate data. Evaluation indicated an increase in knowledge relating to pressure ulcer prevention, treatment strategies, resources required, and the role of the interdisciplinary team. Lack of visible senior nurse leadership; time required to acquire computer skills and to implement new guidelines; and difficulties with the computer system were identified as barriers. There is a need for a comprehensive, supported and sustained approach to implementation of evidence-based practice for pressure ulcer prevention and treatment, greater understanding of organization-specific barriers, and mechanisms for addressing the barriers.

Addressing excess risk of overdose among recently incarcerated people in the USA: harm reduction interventions in correctional settings.

PubMed

Brinkley-Rubinstein, Lauren; Cloud, David H; Davis, Chelsea; Zaller, Nickolas; Delany-Brumsey, Ayesha; Pope, Leah; Martino, Sarah; Bouvier, Benjamin; Rich, Josiah

2017-03-13

Purpose The purpose of this paper is to discuss overdose among those with criminal justice experience and recommend harm reduction strategies to lessen overdose risk among this vulnerable population. Design/methodology/approach Strategies are needed to reduce overdose deaths among those with recent incarceration. Jails and prisons are at the epicenter of the opioid epidemic but are a largely untapped setting for implementing overdose education, risk assessment, medication assisted treatment, and naloxone distribution programs. Federal, state, and local plans commonly lack corrections as an ingredient in combating overdose. Harm reduction strategies are vital for reducing the risk of overdose in the post-release community. Findings Therefore, the authors recommend that the following be implemented in correctional settings: expansion of overdose education and naloxone programs; establishment of comprehensive medication assisted treatment programs as standard of care; development of corrections-specific overdose risk assessment tools; and increased collaboration between corrections entities and community-based organizations. Originality/value In this policy brief the authors provide recommendations for implementing harm reduction approaches in criminal justice settings. Adoption of these strategies could reduce the number of overdoses among those with recent criminal justice involvement.

Guideline attribute and implementation preferences among physicians in multiple health systems.

PubMed

Stone, Tamara T; Schweikhart, Sharon B; Mantese, Annamarie; Sonnad, Seema S

2005-01-01

Although practice guidelines are effective in assisting providers with clinical decision making, ineffective implementation strategies often prevent their use in practice. This study aimed to understand physician preferences for guideline format, placement, content, evidence, and learning strategies in different clinical environments. Semistructured telephone interviews were conducted with 500 randomly selected physicians from 4 major US health systems who were involved in the treatment of patients with acute myocardial infarction or pediatric asthma. Paired sample t tests and Tukey's method of comparisons determined the relative ranking of physicians' guideline implementation preferences. Physicians preferred guidelines located on the front of the patient chart, in palm pilots, or in progress notes and presented as flow charts/flow diagrams, algorithms, or preprinted orders that contain strategies to minimize readmits/encourage self-management and immediate treatment flows. Discussions with colleagues and continuing medical education are the most effective strategies for encouraging guideline use, and randomized controlled trials remain the most persuasive medical evidence. Health care organizations must align guideline implementation efforts with physician preferences to encourage utilization. The results of this study reveal systematic physician preferences for guideline implementation that can be applied to clinical settings to encourage guideline use by physicians.

Management and Treatment of Human Lice

PubMed Central

Sangaré, Abdoul Karim; Doumbo, Ogobara K.

2016-01-01

Of the three lice (head, body, and pubic louse) that infest humans, the body louse is the species involved in epidemics of louse-borne typhus, trench fever, and relapsing fever, but all the three cause pediculosis. Their infestations occur today in many countries despite great efforts to maintain high standards of public health. In this review, literature searches were performed through PubMed, Medline, Google Scholar, and EBSCOhost, with key search words of “Pediculus humanus”, “lice infestation”, “pediculosis”, and “treatment”; and controlled clinical trials were viewed with great interest. Removing lice by hand or with a lice comb, heating infested clothing, and shaving the scalp were some of the oldest methods of controlling human lice. Despite the introduction of other resources including cresol, naphthalene, sulfur, mercury, vinegar, petroleum, and insecticides, the numbers of lice infestation cases and resistance have increased. To date, viable alternative treatments to replace insecticides have been developed experimentally in vitro. Today, the development of new treatment strategies such as symbiotic treatment and synergistic treatment (antibiotics + ivermectin) in vitro has proved effective and is promising. Here, we present an overview on managing and treating human lice and highlight new strategies to more effectively fight pediculosis and prevent resistance. PMID:27529073

Becoming Therapeutic Agents: A Grounded Theory of Mothers' Process When Implementing Cognitive Behavioural Therapy at Home with an Anxious Child.

PubMed

Pishva, Rana

2017-05-01

The premise of parent-centred programmes for parents of anxious children is to educate and train caregivers in the sustainable implementation of cognitive behaviour therapy (CBT) in the home. The existing operationalization of parent involvement, however, does not address the systemic, parent or child factors that could influence this process. The qualitative approach of grounded theory was employed to examine patterns of action and interaction involved in the complex process of carrying out CBT with one's child in one's home. A grounded theory goes beyond the description of a process, offering an explanatory theory that brings taken-for-granted meanings and processes to the surface. The theory that emerged from the analysis suggests that CBT implementation by mothers of anxious children is characterized by the evolution of mothers' perception of their child and mothers' perception of their role as well as a shift from reacting with emotion to responding pragmatically to the child. Changes occur as mothers recognize the crisis, make links between the treatment rationale, child's symptoms and their own parenting strategies, integrate tenets of CBT for anxiety and eventually focus on sustaining therapeutic gains through natural life transitions. The theory widens our understanding of mothers' role, therapeutic engagement, process, and decision-making. The theory also generates new hypotheses regarding parent involvement in the treatment of paediatric anxiety disorders and proposes novel research avenues that aim to maximize the benefits of parental involvement in the treatment of paediatric anxiety disorders. Copyright © 2016 John Wiley & Sons, Ltd. Mothers of anxious youth who take part in parent-centred programmes experience a shift in their perception of the child and of their role. Parental strategy after CBT implementation shifts from emotional empathy to cognitive empathy. Mothers experience significant challenges and require additional support in prevention of relapse and knowledge translation. Copyright © 2016 John Wiley & Sons, Ltd.

Using Goal Achievement Training in juvenile justice settings to improve substance use services for youth on community supervision.

PubMed

Fisher, Jacqueline Horan; Becan, Jennifer E; Harris, Philip W; Nager, Alexis; Baird-Thomas, Connie; Hogue, Aaron; Bartkowski, John P; Wiley, Tisha

2018-04-30

The link between substance use and involvement in the juvenile justice system has been well established. Justice-involved youth tend to have higher rates of drug use than their non-offending peers. At the same time, continued use can contribute to an elevated risk of recidivism, which leads to further, and oftentimes more serious, involvement with the juvenile justice system. Because of these high rates of use, the juvenile justice system is well positioned to help identify youth with substance use problems and connect them to treatment. However, research has found that only about 60% of juvenile probation agencies screen all youth for substance involvement, and even fewer provide comprehensive assessment or help youth enroll in substance use treatment. This paper describes an integrated training curriculum that was developed to help juvenile justice agencies improve their continuum of care for youth probationers with substance use problems. Goal Achievement Training (GAT) provides a platform for continuous quality improvement via two sessions delivered onsite to small groups of staff from juvenile justice and behavioral health agencies. In the first session, participants are taught to identify goals and goal steps for addressing identified areas of unmet need (i.e., screening, assessment, and linkage to treatment services). In the second session, participants learn principles and strategies of data-driven decision-making for achieving these goals. This paper highlights GAT as a model for the effective implementation of cost-efficient training strategies designed to increase self-directed quality improvement activities that can be applied to any performance domain within juvenile justice settings. Efforts to monitor implementation fidelity of GAT within the specific context of the juvenile justice settings are highlighted. Challenges to setting the stage for process improvement generally, as well as specific hurdles within juvenile justice settings are discussed, as are next steps in disseminating findings regarding the fidelity to and effectiveness of GAT in this unique context. Clinical Trials Registration number - NCT02672150 .

Quest for certainty regarding early discharge in paediatric low-risk febrile neutropenia: a multicentre qualitative focus group discussion study involving patients, parents and healthcare professionals in the UK

PubMed Central

Phillips, Bob; Stewart, Lesley A; Atkin, Karl

2018-01-01

Objectives A systematic review of paediatric low-risk febrile neutropenia found that outpatient care is safe, with low rates of treatment failure. However, this review, and a subsequent meta-ethnography, suggested that early discharge of these patients may not be acceptable to key stakeholders. This study aimed to explore experiences and perceptions of patients, parents and healthcare professionals involved in paediatric febrile neutropenia care in the UK. Setting Three different centres within the UK, purposively selected from a national survey on the basis of differences in their service structure and febrile neutropenia management. Participants Thirty-two participants were included in eight focus group discussions. Primary outcomes Experiences and perceptions of paediatric febrile neutropenia care, including possible future reductions in therapy. Results Participants described a quest for certainty, in which they attempted to balance the uncertainty involved in understanding, expressing and negotiating risk with the illusion of certainty provided by strict protocols. Participants assessed risk using both formal and informal stratification tools, overlaid with emotional reactions to risk and experiences of risk within other situations. The benefits of certainty provided by protocols were counterbalanced by frustration at their strict constraints. The perceived benefits and harms of previous inpatient care informed participants’ appraisals of future treatment strategies. Conclusions This study highlighted the previously underestimated harms of admission for febrile neutropenia and the paternalistic nature of decision making, along with the frustrations and challenges for all parties involved in febrile neutropenia care. It demonstrates how the same statistics, generated by systematic reviews, can be used by key stakeholders to interpret risk differently, and how families in particular can view the harms of therapeutic options as different from the outcomes used within the literature. It justifies a reassessment of current treatment strategies for these children and further exploration of the potential to introduce shared decision making. PMID:29764879

A Molecular Approach to Epilepsy Management: from Current Therapeutic Methods to Preconditioning Efforts.

PubMed

Amini, Elham; Rezaei, Mohsen; Mohamed Ibrahim, Norlinah; Golpich, Mojtaba; Ghasemi, Rasoul; Mohamed, Zahurin; Raymond, Azman Ali; Dargahi, Leila; Ahmadiani, Abolhassan

2015-08-01

Epilepsy is the most common and chronic neurological disorder characterized by recurrent unprovoked seizures. The key aim in treating patients with epilepsy is the suppression of seizures. An understanding of focal changes that are involved in epileptogenesis may therefore provide novel approaches for optimal treatment of the seizure. Although the actual pathogenesis of epilepsy is still uncertain, recently growing lines of evidence declare that microglia and astrocyte activation, oxidative stress and reactive oxygen species (ROS) production, mitochondria dysfunction, and damage of blood-brain barrier (BBB) are involved in its pathogenesis. Impaired GABAergic function in the brain is probably the most accepted hypothesis regarding the pathogenesis of epilepsy. Clinical neuroimaging of patients and experimental modeling have demonstrated that seizures may induce neuronal apoptosis. Apoptosis signaling pathways are involved in the pathogenesis of several types of epilepsy such as temporal lobe epilepsy (TLE). The quality of life of patients is seriously affected by treatment-related problems and also by unpredictability of epileptic seizures. Moreover, the available antiepileptic drugs (AED) are not significantly effective to prevent epileptogenesis. Thus, novel therapies that are proficient to control seizure in people who are suffering from epilepsy are needed. The preconditioning method promises to serve as an alternative therapeutic approach because this strategy has demonstrated the capability to curtail epileptogenesis. For this reason, understanding of molecular mechanisms underlying brain tolerance induced by preconditioning is crucial to delineate new neuroprotective ways against seizure damage and epileptogenesis. In this review, we summarize the work to date on the pathogenesis of epilepsy and discuss recent therapeutic strategies in the treatment of epilepsy. We will highlight that novel therapy targeting such as preconditioning process holds great promise. In addition, we will also highlight the role of gene reprogramming and mitochondrial biogenesis in the preconditioning-mediated neuroprotective events.

Continuous tooth replacement: the possible involvement of epithelial stem cells.

PubMed

Huysseune, Ann; Thesleff, Irma

2004-06-01

Epithelial stem cells have been identified in integumental structures such as hairs and continuously growing teeth of various rodents, and in the gut. Here we propose the involvement of epithelial stem cells in the continuous tooth replacement that characterizes non-mammalian vertebrates, as exemplified by the zebrafish. Arguments are based on morphological observations of tooth renewal in the zebrafish and on the similarities between molecular control of hair and tooth formation. Dissection of the molecular cascades underlying the regulation of the epithelial stem cell niche might open perspectives for new regenerative treatment strategies in clinical dentistry. Copyright 2004 Wiley Periodicals, Inc.

Surgery-first orthognathic approach case series: Salient features and guidelines

PubMed Central

Gandedkar, Narayan H; Chng, Chai Kiat; Tan, Winston

2016-01-01

Conventional orthognathic surgery treatment involves a prolonged period of orthodontic treatment (pre- and post-surgery), making the total treatment period of 3–4 years too exhaustive. Surgery-first orthognathic approach (SFOA) sees orthognathic surgery being carried out first, followed by orthodontic treatment to align the teeth and occlusion. Following orthognathic surgery, a period of rapid metabolic activity within tissues ensues is known as the regional acceleratory phenomenon (RAP). By performing surgery first, RAP can be harnessed to facilitate efficient orthodontic treatment. This phenomenon is believed to be a key factor in the notable reduction in treatment duration using SFOA. This article presents two cases treated with SFOA with emphasis on “case selection, treatment strategy, merits, and limitations” of SFOA. Further, salient features comparison of “conventional orthognathic surgery” and “SFOA” with an overview of author's SFOA treatment protocol is enumerated. PMID:26998476

Visualizing topography: Effects of presentation strategy, gender, and spatial ability

NASA Astrophysics Data System (ADS)

McAuliffe, Carla

2003-10-01

This study investigated the effect of different presentation strategies (2-D static visuals, 3-D animated visuals, and 3-D interactive, animated visuals) and gender on achievement, time-spent-on visual treatment, and attitude during a computer-based science lesson about reading and interpreting topographic maps. The study also examined the relationship of spatial ability and prior knowledge to gender, achievement, and time-spent-on visual treatment. Students enrolled in high school chemistry-physics were pretested and given two spatial ability tests. They were blocked by gender and randomly assigned to one of three levels of presentation strategy or the control group. After controlling for the effects of spatial ability and prior knowledge with analysis of covariance, three significant differences were found between the versions: (a) the 2-D static treatment group scored significantly higher on the posttest than the control group; (b) the 3-D animated treatment group scored significantly higher on the posttest than the control group; and (c) the 2-D static treatment group scored significantly higher on the posttest than the 3-D interactive animated treatment group. Furthermore, the 3-D interactive animated treatment group spent significantly more time on the visual screens than the 2-D static treatment group. Analyses of student attitudes revealed that most students felt the landform visuals in the computer-based program helped them learn, but not in a way they would describe as fun. Significant differences in attitude were found by treatment and by gender. In contrast to findings from other studies, no gender differences were found on either of the two spatial tests given in this study. Cognitive load, cognitive involvement, and solution strategy are offered as three key factors that may help explain the results of this study. Implications for instructional design include suggestions about the use of 2-D static, 3-D animated and 3-D interactive animations as well as a recommendation about the inclusion of pretests in similar instructional programs. Areas for future research include investigating the effects of combinations of presentation strategies, continuing to examine the role of spatial ability in science achievement, and gaining cognitive insights about what it is that students do when learning to read and interpret topographic maps.

A worldwide comparison of the management of surgical treatment of advanced oral cancer.

PubMed

Kansy, Katinka; Mueller, Andreas Albert; Mücke, Thomas; Koersgen, Friederike; Wolff, Klaus Dietrich; Zeilhofer, Hans-Florian; Hölzle, Frank; Pradel, Winnie; Schneider, Matthias; Kolk, Andreas; Smeets, Ralf; Acero, Julio; Haers, Piet; Ghali, G E; Hoffmann, Jürgen

2018-03-01

Microvascular surgery following tumor resection has become an important field of oral and maxillofacial surgery (OMFS). Following the results from management of T1/T2 floor-of-mouth and tongue squamous cell carcinoma (SCC) in German-speaking countries, Europe, and worldwide, this paper presents specific concepts for the management of resection and reconstruction of T3/T4 SCC of the maxillary and mandibular alveolar process and tongue. The DÖSAK questionnaire was distributed in three different phases to a growing number of maxillofacial units worldwide. Within this survey, clinical patient settings were presented to participants and center-specific treatment strategies were evaluated. A total of 188 OMFS units from 36 different countries documented their treatment strategies for T3/T4 maxillary and mandibular alveolar process and tongue SCC. The extent of surgical resections and subsequent reconstructions is more consistent than with T1/T2 tumors, although the controversy surrounding continuity resections and mandible-sparing procedures remains. For continuity resection of the mandible the fibula free flap is the most frequently used bone replacement, whereas maxilla reconstruction concepts are less consistent, ranging from locoregional coverage concepts and different microvascular reconstruction options to treatment via obturator prosthesis. Results from treatment strategies for T3/T4 tumors underline the limited evidence for the appropriate amount of resection and subsequent reconstruction process, especially in cases involving the mandible. Prospective randomized trials will be necessary in the long term to establish valid treatment guidelines. Copyright © 2018 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

The art and skill of delivering culturally responsive trauma-focused cognitive behavioral therapy in Tanzania and Kenya.

PubMed

Woods-Jaeger, Briana A; Kava, Christine M; Akiba, Christopher F; Lucid, Leah; Dorsey, Shannon

2017-03-01

This study explored the facilitators, barriers, and strategies used to deliver a child mental health evidence-based treatment (EBT), trauma-focused cognitive behavioral therapy (TF-CBT), in a culturally responsive manner. In low- and middle-income countries most individuals with mental health problems do not receive treatment due to a shortage of mental health professionals. One approach to addressing this problem is task-sharing, in which lay counselors are trained to deliver mental health treatment. Combining this approach with a focus on EBT provides a strategy for bridging the mental health treatment gap. However, little is known about how western-developed EBTs are delivered in a culturally responsive manner. Semistructured qualitative interviews were conducted with 12 TF-CBT lay counselors involved in a large randomized controlled trial of TF-CBT in Kenya and Tanzania. An inductive approach was used to analyze the data. Lay counselors described the importance of being responsive to TF-CBT participants' customs, beliefs, and socioeconomic conditions and highlighted the value of TF-CBT for their community. They also discussed the importance of partnering with other organizations to address unmet socioeconomic needs. The findings from this study provide support for the acceptability and appropriateness of TF-CBT as a treatment approach for improving child mental health. Having a better understanding of the strategies used by lay counselors to ensure that treatment is relevant to the cultural and socioeconomic context of participants can help to inform the implementation of future EBTs. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Fabry nephropathy: a review - how can we optimize the management of Fabry nephropathy?

PubMed

Waldek, Stephen; Feriozzi, Sandro

2014-05-06

Fabry disease is a rare, X-linked, lysosomal storage disease caused by mutations in the gene encoding the enzyme alpha-galactosidase A. Complete or partial deficiency in this enzyme leads to intracellular accumulation of globotriaosylceramide (Gb3) and related glycosphingolipids in many cell types throughout the body, including the kidney. Progressive accumulation of Gb3 in podocytes, epithelial cells and the tubular cells of the distal tubule and loop of Henle contribute to the renal symptoms of Fabry disease, which manifest as proteinuria and reduced glomerular filtration rate leading to chronic kidney disease and progression to end-stage renal disease. Early diagnosis and timely initiation of treatment of Fabry renal disease is an important facet of disease management. Initiating treatment with enzyme replacement therapy (ERT; agalsidase alfa, Replagal®, Shire; agalsidase beta, Fabrazyme®, Genzyme) as part of a comprehensive strategy to prevent complications of the disease, may be beneficial in stabilizing renal function or slowing its decline. Early initiation of ERT may also be more effective than initiating therapy in patients with more advanced disease. Several strategies are required to complement the use of ERT and treat the myriad of associated symptoms and organ involvements. In particular, patients with renal Fabry disease are at risk of cardiovascular events, such as high blood pressure, cardiac arrhythmias and stroke. This review discusses the management of renal involvement in Fabry disease, including diagnosis, treatments, and follow-up, and explores recent advances in the use of biomarkers to assist with diagnosis, monitoring disease progression and response to treatment.

Fabry nephropathy: a review – how can we optimize the management of Fabry nephropathy?

PubMed Central

2014-01-01

Fabry disease is a rare, X-linked, lysosomal storage disease caused by mutations in the gene encoding the enzyme alpha-galactosidase A. Complete or partial deficiency in this enzyme leads to intracellular accumulation of globotriaosylceramide (Gb3) and related glycosphingolipids in many cell types throughout the body, including the kidney. Progressive accumulation of Gb3 in podocytes, epithelial cells and the tubular cells of the distal tubule and loop of Henle contribute to the renal symptoms of Fabry disease, which manifest as proteinuria and reduced glomerular filtration rate leading to chronic kidney disease and progression to end-stage renal disease. Early diagnosis and timely initiation of treatment of Fabry renal disease is an important facet of disease management. Initiating treatment with enzyme replacement therapy (ERT; agalsidase alfa, Replagal®, Shire; agalsidase beta, Fabrazyme®, Genzyme) as part of a comprehensive strategy to prevent complications of the disease, may be beneficial in stabilizing renal function or slowing its decline. Early initiation of ERT may also be more effective than initiating therapy in patients with more advanced disease. Several strategies are required to complement the use of ERT and treat the myriad of associated symptoms and organ involvements. In particular, patients with renal Fabry disease are at risk of cardiovascular events, such as high blood pressure, cardiac arrhythmias and stroke. This review discusses the management of renal involvement in Fabry disease, including diagnosis, treatments, and follow-up, and explores recent advances in the use of biomarkers to assist with diagnosis, monitoring disease progression and response to treatment. PMID:24886109

The epigenetically regulated miR-494 associates with stem-cell phenotype and induces sorafenib resistance in hepatocellular carcinoma.

PubMed

Pollutri, Daniela; Patrizi, Clarissa; Marinelli, Sara; Giovannini, Catia; Trombetta, Elena; Giannone, Ferdinando A; Baldassarre, Maurizio; Quarta, Santina; Vandewynckel, Y P; Vandierendonck, A; Van Vlierberghe, H; Porretti, Laura; Negrini, Massimo; Bolondi, Luigi; Gramantieri, Laura; Fornari, Francesca

2018-01-05

Hepatocellular carcinoma (HCC) represents the second cause of cancer-related mortality worldwide and is associated with poor prognosis, especially in patients not amenable for curative treatments. The multi-kinase inhibitor sorafenib represents the first-line treatment option for advanced HCC; nevertheless, its effectiveness is limited due to tumor heterogeneity as well as innate or acquired drug resistance, raising the need for new therapeutic strategies. MicroRNAs (miRNAs) involvement in treatment response as well as their safety and efficacy in preclinical models and clinical trials have been widely documented in the oncologic field, including HCC. Here, we identified miR-494 upregulation in a subgroup of human and rat HCCs with stem cell-like characteristics, as well as multiple epigenetic mechanisms involved in its aberrant expression in HCC cell lines and patients. Moreover, we identified p27, puma and pten among miR-494 targets, contributing to speed up cell cycle progression, enhance survival potential in stressful conditions and increase invasive and clonogenic capabilities. MiR-494 overexpression increased sorafenib resistance via mTOR pathway activation in HCC cell lines and, in line, high miR-494 levels associated with decreased sorafenib response in two HCC animal models. A sorafenib-combined anti-miR-494-based strategy revealed an enhanced anti-tumor potential with respect to sorafenib-only treatment in our HCC rat model. In conclusion, our findings suggested miR-494 as a possible therapeutic target as well as a candidate biomarker for patient stratification in advanced HCC.

Cancer care in Romania: challenges and pitfalls of children's and adolescents' multifaceted involvement.

PubMed

Badarau, Domnita O; De Clercq, Eva; Wangmo, Tenzin; Dragomir, Monica; Miron, Ingrid; Kühne, Thomas; Elger, Bernice S

2016-12-01

Communication about diagnosis and medical treatment for children suffering from life-threatening illnesses is complex. It is a primary step in involving underage patients and families in care and lays the foundation for obtaining parental permission and patient assent for treatment. In practice child participation in care is often difficult to obtain due to patients' different and sometimes fluctuating preferences, but also parents' protective strategies. Physicians may be susceptible to parental wishes to limit information and feel uncomfortable discussing issues related to uncertainty of cure with patients. A qualitative study in Romanian paediatric oncology units was conducted to explore children's involvement from the perspectives of parents and oncologists. Interviews with participants discussed 18 patient cases. Data were transcribed and thematic analysis was used to interpret and mine patients' involvement during treatment. Different facets of patient participation were identified: restricting, widening and enhancing involvement. A fourth category, unintentional involvement, occurred for all patients due to children's observations during long-term hospitalisations and access to Internet. Uncertainty overarched parental attitudes regarding the extent to which children should be included. Physicians usually complied with parental wishes to limit involvement, but together with parents involved patients at least in a practical way. Adults' protective attitude may backfire, as adolescents' online searches often expose patients to worse-case scenarios. Further research should acknowledge the hazards of restricted diagnosis disclosure and develop clinician tools to support families in communicating with patients. This should be paralleled by physician efforts to elicit patients' needs regarding participation. 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/.

MicroRNAs Change the Landscape of Cancer Resistance.

PubMed

Zhu, Jun; Zhu, Wei; Wu, Wei

2018-01-01

One of the major challenges in the cancer treatment is the development of drug resistance. It represents a major obstacle to curing cancer with constrained efficacy of both conventional chemotherapy and targeted therapies, even recent immune checkpoint blockade therapy. Deciphering the mechanisms of resistance is critical to further understanding the multifactorial pathways involved, and developing more specific targeted treatments. To date, numerous studies have reported the potential role of microRNAs (miRNAs) in the resistance to various cancer treatments. MicroRNAs are a family of small noncoding RNAs that regulate gene expression by sequence-specific targeting of mRNAs causing translational repression or mRNA degradation. More than 1200 validated human miRNAs have been identified in human genome. While one miRNA can regulate hundreds of targets, a single target can also be affected by multiple miRNAs. Evidence suggests that dysregulation of specific miRNAs may be involved in the acquisition of resistance, thereby modulating the sensitivity of cancer cells to treatment. Therefore, manipulation of miRNAs may be an attractive strategy for more effective individualized therapies through reprograming resistant network in cancer cells.

Cardiac resynchronization therapy in a patient with amyloid cardiomyopathy.

PubMed

Zizek, David; Cvijić, Marta; Zupan, Igor

2013-06-01

Cardiac involvement in systemic light chain amyloidosis carries poor prognosis. Amyloid deposition in the myocardium can alter regional left ventricular contraction and cause dyssynchrony. Cardiac resynchronization therapy (CRT) is an effective treatment strategy for patients with advanced heart failure and echocardiographic dyssynchrony. We report a clinical and echocardiographic response of a patient with amyloid cardiomyopathy, treated with a combination of chemotherapy and CRT.

Seborrheic Dermatitis and Dandruff: A Comprehensive Review

PubMed Central

Borda, Luis J.; Wikramanayake, Tongyu C.

2016-01-01

Seborrheic Dermatitis (SD) and dandruff are of a continuous spectrum of the same disease that affects the seborrheic areas of the body. Dandruff is restricted to the scalp, and involves itchy, flaking skin without visible inflammation. SD can affect the scalp as well as other seborrheic areas, and involves itchy and flaking or scaling skin, inflammation and pruritus. Various intrinsic and environmental factors, such as sebaceous secretions, skin surface fungal colonization, individual susceptibility, and interactions between these factors, all contribute to the pathogenesis of SD and dandruff. In this review, we summarize the current knowledge on SD and dandruff, including epidemiology, burden of disease, clinical presentations and diagnosis, treatment, genetic studies in humans and animal models, and predisposing factors. Genetic and biochemical studies and investigations in animal models provide further insight on the pathophysiology and strategies for better treatment. PMID:27148560

Multimodal Surgical and Medical Treatment for Extensive Rhinocerebral Mucormycosis in an Elderly Diabetic Patient: A Case Report and Literature Review

PubMed Central

Pirrello, Roberto; Guadagnino, Giuliana; Richiusa, Pierina; Lo Casto, Antonio; Sarno, Caterina; Moschella, Francesco; Cabibi, Daniela

2014-01-01

Diabetes is a well-known risk factor for invasive mucormycosis with rhinocerebral involvement. Acute necrosis of the maxilla is seldom seen and extensive facial bone involvement is rare in patients with rhino-orbital-cerebral mucormycosis. An aggressive surgical approach combined with antifungal therapy is usually necessary. In this report, we describe the successful, personalized medical and surgical management of extensive periorbital mucormycosis in an elderly diabetic, HIV-negative woman. Mono- or combination therapy with liposomal amphotericin B (L-AmB) and posaconazole (PSO) and withheld debridement is discussed. The role of aesthetic plastic surgery to preserve the patient's physical appearance is also reported. Any diabetic patient with sinonasal disease, regardless of their degree of metabolic control, is a candidate for prompt evaluation to rule out mucormycosis. Therapeutic and surgical strategies and adjunctive treatments are essential for successful disease management. These interventions may include combination therapy. Finally, a judicious multimodal treatment approach can improve appearance and optimize outcome in elderly patients. PMID:24982678

Ion channels of the mammalian urethra

PubMed Central

Kyle, Barry D

2014-01-01

The mammalian urethra is a muscular tube responsible for ensuring that urine remains in the urinary bladder until urination. In order to prevent involuntary urine leakage, the urethral musculature must be capable of constricting the urethral lumen to an extent that exceeds bladder intravesicular pressure during the urine-filling phase. The main challenge in anti-incontinence treatments involves selectively-controlling the excitability of the smooth muscles in the lower urinary tract. Almost all strategies to battle urinary incontinence involve targeting the bladder and as a result, this tissue has been the focus for the majority of research and development efforts. There is now increasing recognition of the value of targeting the urethral musculature in the treatment and management of urinary incontinence. Newly-identified and characterized ion channels and pathways in the smooth muscle of the urethra provides a range of potential therapeutic targets for the treatment of urinary incontinence. This review provides a summary of the current state of knowledge of the ion channels discovered in urethral smooth muscle cells that regulate their excitability. PMID:25483582

[Head and neck paragangliomas: An interdisciplinary challenge].

PubMed

Künzel, J; Bahr, K; Hainz, M; Rossmann, H; Matthias, C

2015-12-01

Current treatment strategies for head and neck paragangliomas are moving away from radical resection and toward surgical tumor reduction, in order to preserve function and reduce morbidity. Radiotherapy modalities are alternative primary treatment options. A PubMed search of the relevant literature on genetics and treatment of head and neck paragangliomas was conducted. The rapid progress made in genetic research was mainly triggered by two factors: firstly, the establishment of central registries for paraganglioma patients and secondly, the availability of next-generation sequencing methods. Exome sequencing and a gene-panel sequencing approach have already been successfully applied to paraganglioma syndromes. The latter method in particular is rapid and cost-effective, and may soon replace complex genotyping algorithms. The literature provides good evidence that diversified modern treatment options are available to realize individual treatment concepts for almost all paraganglioma manifestations. Generally, small and symptomatic tumors should be completely resected, particularly in younger patients. Considering the patient's age, symptoms, morbidity risk, and comorbidities, larger tumors should be surgically treated in a function-preserving manner. In these cases, primary radiotherapy is an equivalent alternative option. A "wait and scan" strategy is possible in selected cases. The potential morbidity of surgical treatment must be weighed against the expectable quality of life. Comprehensive consultation with the patient about possible treatment modalities is mandatory. Treatment decision making should involve a multidisciplinary team of experts.

Recommendations to Facilitate Expanded Access to Investigational Therapies for Seriously Ill Patients

PubMed Central

Jerome, Rebecca N.; Edwards, Terri L.; Boswell, Haley C.; Bernard, Gordon R.; Harris, Paul A.; Pulley, Jill M.

2015-01-01

When clinical trial enrollment is not an option for seriously ill patients whose illnesses have not responded to approved treatment options, those patients and their physicians may consider gaining access to investigational therapies through a pathway established by the Food and Drug Administration (FDA) called expanded access. However, recent events have highlighted the challenging dynamics involved in accessing investigational therapies through expanded access that include a complex interplay of factors involving the patient, physician, drug company, FDA, and, increasingly, social media. The authors offer several potential strategies to streamline what is otherwise an arduous process for all involved. (1) The drug company should prospectively determine whether it will establish an expanded access program for specific drugs. (2) A central clearinghouse for companies should support registration of expanded access drugs for suitable patients. (3) The determination of whether a patient fits criteria would be made by an independent review board of clinicians. (4) An independent coordinating center is needed; academic health centers are ideally suited for that role. (5) Adequate financing of the costs of therapy need to be in place to make expanded access a reality, given frequent lack of payor coverage for therapies. (6) Further enhancement of regulatory pathways, approaches, or rules would promote expanded access. (7) Patients should explicitly acknowledge the limited data available. (8) There should be a shared, secure, technical platform to facilitate expanded access. All the authors’ strategies present important prospects for improving treatment options for the most seriously ill patients. PMID:26445080

Human cytosolic glutathione-S-transferases: quantitative analysis of expression, comparative analysis of structures and inhibition strategies of isozymes involved in drug resistance.

PubMed

Mohana, Krishnamoorthy; Achary, Anant

2017-08-01

Glutathione-S-transferase (GST) inhibition is a strategy to overcome drug resistance. Several isoforms of human GSTs are present and they are expressed in almost all the organs. Specific expression levels of GSTs in various organs are collected from the human transcriptome data and analysis of the organ-specific expression of GST isoforms is carried out. The variations in the level of expressions of GST isoforms are statistically significant. The GST expression differs in diseased conditions as reported by many investigators and some of the isoforms of GSTs are disease markers or drug targets. Structure analysis of various isoforms is carried out and literature mining has been performed to identify the differences in the active sites of the GSTs. The xenobiotic binding H site is classified into H1, H2, and H3 and the differences in the amino acid composition, the hydrophobicity and other structural features of H site of GSTs are discussed. The existing inhibition strategies are compared. The advent of rational drug design, mechanism-based inhibition strategies, availability of high-throughput screening, target specific, and selective inhibition of GST isoforms involved in drug resistance could be achieved for the reversal of drug resistance and aid in the treatment of diseases.

Cartilage tissue engineering: From biomaterials and stem cells to osteoarthritis treatments.

PubMed

Vinatier, C; Guicheux, J

2016-06-01

Articular cartilage is a non-vascularized and poorly cellularized connective tissue that is frequently damaged as a result of trauma and degenerative joint diseases such as osteoarthrtis. Because of the absence of vascularization, articular cartilage has low capacity for spontaneous repair. Today, and despite a large number of preclinical data, no therapy capable of restoring the healthy structure and function of damaged articular cartilage is clinically available. Tissue-engineering strategies involving the combination of cells, scaffolding biomaterials and bioactive agents have been of interest notably for the repair of damaged articular cartilage. During the last 30 years, cartilage tissue engineering has evolved from the treatment of focal lesions of articular cartilage to the development of strategies targeting the osteoarthritis process. In this review, we focus on the different aspects of tissue engineering applied to cartilage engineering. We first discuss cells, biomaterials and biological or environmental factors instrumental to the development of cartilage tissue engineering, then review the potential development of cartilage engineering strategies targeting new emerging pathogenic mechanisms of osteoarthritis. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Developmental Biology and Regenerative Medicine: Addressing the Vexing Problem of Persistent Muscle Atrophy in the Chronically Torn Human Rotator Cuff.

PubMed

Meyer, Gretchen A; Ward, Samuel R

2016-05-01

Persistent muscle atrophy in the chronically torn rotator cuff is a significant obstacle for treatment and recovery. Large atrophic changes are predictive of poor surgical and nonsurgical outcomes and frequently fail to resolve even following functional restoration of loading and rehabilitation. New insights into the processes of muscle atrophy and recovery gained through studies in developmental biology combined with the novel tools and strategies emerging in regenerative medicine provide new avenues to combat the vexing problem of muscle atrophy in the rotator cuff. Moving these treatment strategies forward likely will involve the combination of surgery, biologic/cellular agents, and physical interventions, as increasing experimental evidence points to the beneficial interaction between biologic therapies and physiologic stresses. Thus, the physical therapy profession is poised to play a significant role in defining the success of these combinatorial therapies. This perspective article will provide an overview of the developmental biology and regenerative medicine strategies currently under investigation to combat muscle atrophy and how they may integrate into the current and future practice of physical therapy. © 2016 American Physical Therapy Association.

Ghrelin Serum Concentrations Are Associated with Treatment Response During Lithium Augmentation of Antidepressants.

PubMed

Ricken, Roland; 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

2017-09-01

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. Ghrelin serum concentrations and severity of depression were measured in 85 acute depressive patients before and after 4 weeks of lithium augmentation. 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). 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. © The Author 2017. Published by Oxford University Press on behalf of CINP.

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. PMID:28911006

Gastro-oesophageal cancer: facts, myths and surgical folk lore.

PubMed

Park, K G M

2002-12-01

The prognosis of patients with gastric and oesophageal cancers remains poor but increased knowledge of the factors involved in carcinogenesis and a better understanding of the disease process has led to strategies to improve outcomes. These are discussed under the following headings: (1) Prevention of the disease, (2) early detection of tumours, (3) treatment selection and (4) treatment. The likely impact of developments in each of these areas is considered in relation to population-based data from the Scottish Audit of Gastro-Oesophageal Cancer (SAGOC). Although there are a number of novel developments in the management of gastric and oesophageal cancer it is only by the conduct of controlled trials that the value of these will be determined. More immediate improvements in patient care may be derived from rationalisation of existing resources to ensure that all patients benefit from early diagnosis, the appropriate selection and delivery of treatment. One model of care, which may ensure this is the development of managed clinical networks, would maintain the involvement of all units in the management and treatment of upper GI cancers to a level that is possible with the facilities available. At the same time the patients requiring more specialised treatment would benefit from established referral networks

The effect of oilseed consumption on appetite and on the risk of developing type 2 diabetes mellitus.

PubMed

Neves Ribeiro, Daniela; Gonçalves Alfenas, Rita de Cássia; Bressan, Josefina; Brunoro Costa, Neuza Maria

2013-01-01

The prevalence of diabetes mellitus (DM) has rapidly increased worldwide. Excess body fat is an important risk factor for the disease. Strategies have been indicated for the prevention and treatment of DM. Recent studies have associated the consumption of oilseeds resulting in a lower risk of developing obesity and diabetes. It is believed that this effect is associated with low glycemic index and the high fiber content, the unsaturated fatty acids and the magnesium oilseeds. However, the mechanisms involved in appetite and type 2 diabetes control have not been fully elucidated among researchers yet. Thus, the objective of the present article was to critically analyze the articles published on this subject aiming at identifying strategies which may be used in the dietary treatment of diabetes. Copyright © AULA MEDICA EDICIONES 2013. Published by AULA MEDICA. All rights reserved.

Tuberculosis in children and adolescents: Strategies for social workers' interventions.

PubMed

González, Norma E; Angueira, Luciana

2017-12-01

In the care of children and adolescents with tuberculosis (TB), it is necessary to know the difficulties that many families have in accessing health care, obtaining a diagnosis, and receiving a timely treatment. Social workers, along with other members of the health care team, assist in providing access to health care resources and benefits that may favor treatment compliance and strengthen the health of this vulnerable population. Although the purpose of social workers involvement in this disease is to reduce the risk of becoming infected, sick or dying from TB, the current epidemiological situation of this disease in Argentina has faced social workers with the challenge of reconsidering new intervention strategies and revising current objectives. This study addresses their role and proposes actions that may contribute to decreasing TB morbidity and mortality in children and adolescents. Sociedad Argentina de Pediatría.

Wilson’s disease: A review of what we have learned

PubMed Central

Rodriguez-Castro, Kryssia Isabel; Hevia-Urrutia, Francisco Javier; Sturniolo, Giacomo Carlo

2015-01-01

Wilson’s disease (WD), which results from the defective ATP7B protein product, is characterized by impaired copper metabolism and its clinical consequences vary from an asymptomatic state to fulminant hepatic failure, chronic liver disease with or without cirrhosis, neurological, and psychiatric manifestations. A high grade of suspicion is warranted to not miss cases of WD, especially less florid cases with only mild elevation of transaminases, or isolated neuropsychiatric involvement. Screening in first and second relatives of index cases is mandatory, and treatment must commence upon establishment of diagnosis. Treatment strategies include chelators such as D-penicillamine and trientine, while zinc salts act as inductors of methallothioneins, which favor a negative copper balance and a reduction of free plasmatic copper. As an orphan disease, research is lacking in this field, especially regarding therapeutic strategies which are associated with better patient compliance and which could eventually also reverse established injury. PMID:26692151

Antisense oligonucleotides as innovative therapeutic strategy in the treatment of high-grade gliomas.

PubMed

Caruso, Gerardo; Caffo, Mariella; Raudino, Giuseppe; Alafaci, Concetta; Salpietro, Francesco M; Tomasello, Francesco

2010-01-01

Despite the intensive recent research in cancer therapy, the prognosis in patients affected by high-grade gliomas is still very unfavorable. The efficacy of classical anti-cancer strategies is seriously limited by lack of specific therapies against malignant cells. The extracellular matrix plays a pivotal role in processes such as differentiation, apoptosis, and migration in both the normal and the pathologic nervous system. Glial tumors seem to be able to create a favorable environment for the invasion of glioma cells in cerebral parenchyma when they combine with the extracellular matrix via cell surface receptors. Glioma cells synthesize matrix proteins, such as tenascin, laminin, fibronectin that facilitate the tumor cell's motility. New treatments have shown to hit the acting molecules in the tumor growth and to increase the efficacy and minimize the toxicity. Antisense oligonucleotides are synthetic stretches of DNA which hybridize with specific mRNA strands. The specificity of hybridization makes antisense method an interesting strategy to selectively modulate the expression of genes involved in tumorigenesis. In this review we will focus on the mechanisms of action of antisense oligonucleotides and report clinical and experimental studies on the treatment of high-grade gliomas. We will also report the patents of preclinical and/or clinical studies that adopt the antisense oligonucleotide therapy list in cerebral gliomas.

E phage gene transfection associated to chemotherapeutic agents increases apoptosis in lung and colon cancer cells.

PubMed

Rama, Ana R; Prados, Jose; Melguizo, Consolacion; Alvarez, Pablo J; Ortiz, Raúl; Madeddu, Roberto; Aranega, Antonia

2011-01-01

The limited ability of conventional therapies to achieve the long-term survival of metastatic lung and colon cancer patients suggests the need for new treatment options. In this respect, genes encoding cytotoxic proteins have been proposed as a new strategy to enhance the activity of drugs, and combined therapies involving such genes and classical antitumoral drugs have been studied intensively. The E gene from phiX174 encodes a membrane protein with a toxic domain that leads to a decrease in tumour cell growth rates. Therefore, in order to improve the anti-tumour effects of currently used chemotherapeutic drugs on cancer cells, we investigated the association of the E suicide gene with these antineoplastic drugs. The E gene has antitumoral effects in both lung and colon cancer cells. In addition, expression of this gene induces ultrastructural changes in lung cancer transfected cells (A-549), although the significance of these changes remains unknown. The effect of combined therapy (gene and cytotoxic therapy) enhances the inhibition of tumour cell proliferation in comparison to single treatments. Indeed, our in vitro results indicate that an experimental therapeutic strategy based on this combination of E gene therapy and cytotoxic drugs may result in a new treatment strategy for patients with advanced lung and colon cancer.

NEW MOLECULAR MEDICINE-BASED SCAR MANAGEMENT STRATEGIES

PubMed Central

Arno, Anna I; Gauglitz, Gerd G; Barret, Juan P; Jeschke, Marc G

2014-01-01

Keloids and hypertrophic scars are prevalent disabling conditions with still suboptimal treatments. Basic science and molecular-based medicine research has contributed to unravel new bench-to-bedside scar therapies, and to dissect the complex signaling pathways involved. Peptides such as transforming growth factor beta (TGF-β) superfamily, with SMADs, Ski, SnoN, Fussels, endoglin, DS-Sily, Cav-1p, AZX100, thymosin-β4 and other related molecules may emerge as targets to prevent and treat keloids and hypertrophic scars. The aim of this review is to describe the basic complexity of these new molecular scar management strategies, and point out new fibrosis research lines. PMID:24438742

Fathers’ contributions to the management of their child’s long‐term medical condition: a narrative review of the literature

PubMed Central

Swallow, Veronica; Macfadyen, Ann; Santacroce, Sheila J.; Lambert, Heather

2011-01-01

Abstract Context  Fathers’ contributions to the management of long‐term childhood medical conditions are under‐represented in the literature; therefore, the full extent of their involvement is poorly understood by practitioners and researchers, so strategies for promoting their involvement have not yet been fully considered. Objective  To review studies of fathers’ actual contributions in a wide range of conditions, the potential to optimize their contribution through additional interventions by health professionals and a direction for future research. Design  Narrative review of the literature. Methods  CINAHL, Medline, PsychInfo and ERIC databases were searched electronically between the years 1995–2008. The terms adherence, adjustment, child, chronic, compliance, concordance, condition, coping, disease, father, illness, information, long‐term, management/intervention, mother, role, self‐care and treatment were searched for separately and in combination. English language papers reporting primary research were selected and supplemented by hand‐searching reference lists. Thirty‐five papers (arising from 29 studies) met criteria and were selected for narrative review. Results  Five themes were identified: (i) the impact of long‐term conditions on fathers’ ability to promote their child’s well‐being, (ii) factors influencing fathers’ involvement in health care, (iii) personal growth/beneficial effects for fathers, (iv) the impact of father’s involvement on family functioning and (v) strategies that increase fathers’ participation in their child’s health care and in research investigating fathers’ participation. Conclusions  The review suggests that fathers’ involvement in children’s health care can positively impact on fathers’, mothers’ and children’s well‐being and family functioning. A range of strategies are identified to inform the promotion of fathers’ contributions and future research investigating their input. PMID:21624023

Oligo/Polynucleotide-Based Gene Modification: Strategies and Therapeutic Potential

PubMed Central

Sargent, R. Geoffrey; Kim, Soya

2011-01-01

Oligonucleotide- and polynucleotide-based gene modification strategies were developed as an alternative to transgene-based and classical gene targeting-based gene therapy approaches for treatment of genetic disorders. Unlike the transgene-based strategies, oligo/polynucleotide gene targeting approaches maintain gene integrity and the relationship between the protein coding and gene-specific regulatory sequences. Oligo/polynucleotide-based gene modification also has several advantages over classical vector-based homologous recombination approaches. These include essentially complete homology to the target sequence and the potential to rapidly engineer patient-specific oligo/polynucleotide gene modification reagents. Several oligo/polynucleotide-based approaches have been shown to successfully mediate sequence-specific modification of genomic DNA in mammalian cells. The strategies involve the use of polynucleotide small DNA fragments, triplex-forming oligonucleotides, and single-stranded oligodeoxynucleotides to mediate homologous exchange. The primary focus of this review will be on the mechanistic aspects of the small fragment homologous replacement, triplex-forming oligonucleotide-mediated, and single-stranded oligodeoxynucleotide-mediated gene modification strategies as it relates to their therapeutic potential. PMID:21417933

The Rhode Island community responds to opioid overdose deaths.

PubMed

Bowman, Sarah; Engelman, Ariel; Koziol, Jennifer; Mahoney, Linda; Maxwell, Christopher; McKenzie, Michelle

2014-10-01

The challenge of addressing the epidemic of opioid overdose in Rhode Island, and nationwide, is only possible through collaborative efforts among a wide breadth of stakeholders. This article describes the range of efforts by numerous partners that have come together to facilitate community, and treatment-related approaches to address opioid-involved overdose and substance use disorder. Strategies to address this crisis have largely focused on increasing access both to the opioid overdose antidote naloxone and to high quality and timely treatment and recovery services. [Full text available at http://rimed.org/rimedicaljournal-2014-10.asp, free with no login].

“…still waiting for chloroquine”: the challenge of communicating changes in first-line treatment policy for uncomplicated malaria in a remote Kenyan district

PubMed Central

2014-01-01

Background Widespread parasite resistance to first-line treatment for uncomplicated malaria leads to introduction of new drug interventions. Introducing such interventions is complex and sensitive because of stakeholder interests and public resistance. To enhance take up of such interventions, health policy communication strategies need to deliver accurate and accessible information to empower communities with necessary information and address problems of cultural acceptance of new interventions. Objectives To explore community understanding of policy changes in first-line treatment for uncomplicated malaria in Kenya; to evaluate the potential role of policy communication in influencing responses to changes in first-line treatment policy. Methods Data collection involved qualitative strategies in a remote district in the Kenyan Coast: in-depth interviews (n = 29), focus group discussions (n = 14), informal conversations (n = 11) and patient narratives (n = 8). Constant comparative method was used in the analysis. Being malaria-prone and remotely located, the district offered an ideal area to investigate whether or not and how policy communication about a matter as critical as change of treatment policy reaches vulnerable populations. Results Three years after initial implementation (2009), there was limited knowledge or understanding regarding change of first-line treatment from sulphadoxine-pyrimethamine (SP) to artemether-lumefantrine (AL) for treatment of uncomplicated malaria in the study district. The print and electronic media used to create awareness about the drug change appeared to have had little impact. Although respondents were aware of the existence of AL, the drug was known neither by name nor as the official first-line treatment. Depending on individuals or groups, AL was largely viewed negatively. The weaknesses in communication strategy surrounding the change to AL included poor choice of communication tools, confusing advertisements of other drugs and conflicts between patients and providers. Conclusion Effective health policy communication is important for the uptake of new drug interventions and adherence to treatment regimens. Besides, prompt access to effective treatment may not be achieved if beneficiaries are not adequately informed about treatment policy changes. Future changes in treatment policy should ensure that the communication strategy is designed to pass sustained, accurate and effective messages that account for local contexts. PMID:25005337

"…still waiting for chloroquine": the challenge of communicating changes in first-line treatment policy for uncomplicated malaria in a remote Kenyan district.

PubMed

Okungu, Vincent; Gilson, Lucy

2014-07-08

Widespread parasite resistance to first-line treatment for uncomplicated malaria leads to introduction of new drug interventions. Introducing such interventions is complex and sensitive because of stakeholder interests and public resistance. To enhance take up of such interventions, health policy communication strategies need to deliver accurate and accessible information to empower communities with necessary information and address problems of cultural acceptance of new interventions. To explore community understanding of policy changes in first-line treatment for uncomplicated malaria in Kenya; to evaluate the potential role of policy communication in influencing responses to changes in first-line treatment policy. Data collection involved qualitative strategies in a remote district in the Kenyan Coast: in-depth interviews (n = 29), focus group discussions (n = 14), informal conversations (n = 11) and patient narratives (n = 8). Constant comparative method was used in the analysis. Being malaria-prone and remotely located, the district offered an ideal area to investigate whether or not and how policy communication about a matter as critical as change of treatment policy reaches vulnerable populations. Three years after initial implementation (2009), there was limited knowledge or understanding regarding change of first-line treatment from sulphadoxine-pyrimethamine (SP) to artemether-lumefantrine (AL) for treatment of uncomplicated malaria in the study district. The print and electronic media used to create awareness about the drug change appeared to have had little impact. Although respondents were aware of the existence of AL, the drug was known neither by name nor as the official first-line treatment. Depending on individuals or groups, AL was largely viewed negatively. The weaknesses in communication strategy surrounding the change to AL included poor choice of communication tools, confusing advertisements of other drugs and conflicts between patients and providers. Effective health policy communication is important for the uptake of new drug interventions and adherence to treatment regimens. Besides, prompt access to effective treatment may not be achieved if beneficiaries are not adequately informed about treatment policy changes. Future changes in treatment policy should ensure that the communication strategy is designed to pass sustained, accurate and effective messages that account for local contexts.

Basic concepts regarding fracture healing and the current options and future directions in managing bone fractures.

PubMed

Bigham-Sadegh, Amin; Oryan, Ahmad

2015-06-01

Fracture healing is a complex physiological process, which involves a well-orchestrated series of biological events. Repair of large bone defects resulting from trauma, tumours, osteitis, delayed unions, non-unions, osteotomies, arthrodesis and multifragmentary fractures is a current challenge of surgeons and investigators. Different therapeutic modalities have been developed to enhance the healing response and fill the bone defects. Different types of growth factors, stem cells, natural grafts (autografts, allografts or xenografts) and biologic- and synthetic-based tissue-engineered scaffolds are some of the examples. Nevertheless, these organic and synthetic materials and therapeutic agents have some significant limitations, and there are still no well-approved treatment modalities to meet all the expected requirements. Bone tissue engineering is a newer option than the traditional grafts and may overcome many limitations of the bone graft. To select an appropriate treatment strategy in achieving a successful and secure healing, more information concerning injuries of bones, their healing process and knowledge of the factors involved are required. The main goals of this work are to present different treatment modalities of the fractured bones and to explain how fractures normally heal and what factors interfere with fracture healing. This study provides an overview of the processes of fracture healing and discusses the current therapeutic strategies that have been claimed to be effective in accelerating fracture healing. © 2014 The Authors. International Wound Journal © 2014 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

Pathogenesis and treatment of impaired wound healing in diabetes mellitus: new insights.

PubMed

Baltzis, Dimitrios; Eleftheriadou, Ioanna; Veves, Aristidis

2014-08-01

Diabetic foot ulcers (DFUs) are one of the most common and serious complications of diabetes mellitus, as wound healing is impaired in the diabetic foot. Wound healing is a dynamic and complex biological process that can be divided into four partly overlapping phases: hemostasis, inflammation, proliferative and remodeling. These phases involve a large number of cell types, extracellular components, growth factors and cytokines. Diabetes mellitus causes impaired wound healing by affecting one or more biological mechanisms of these processes. Most often, it is triggered by hyperglycemia, chronic inflammation, micro- and macro-circulatory dysfunction, hypoxia, autonomic and sensory neuropathy, and impaired neuropeptide signaling. Research focused on thoroughly understanding these mechanisms would allow for specifically targeted treatment of diabetic foot ulcers. The main principles for DFU treatment are wound debridement, pressure off-loading, revascularization and infection management. New treatment options such as bioengineered skin substitutes, extracellular matrix proteins, growth factors, and negative pressure wound therapy, have emerged as adjunctive therapies for ulcers. Future treatment strategies include stem cell-based therapies, delivery of gene encoding growth factors, application of angiotensin receptors analogs and neuropeptides like substance P, as well as inhibition of inflammatory cytokines. This review provides an outlook of the pathophysiology in diabetic wound healing and summarizes the established and adjunctive treatment strategies, as well as the future therapeutic options for the treatment of DFUs.

Elimination of Taenia solium Transmission in Northern Peru.

PubMed

Garcia, Hector H; Gonzalez, Armando E; Tsang, Victor C W; O'Neal, Seth E; Llanos-Zavalaga, Fernando; Gonzalvez, Guillermo; Romero, Jaime; Rodriguez, Silvia; Moyano, Luz M; Ayvar, Viterbo; Diaz, Andre; Hightower, Allen; Craig, Philip S; Lightowlers, Marshall W; Gauci, Charles G; Leontsini, Elli; Gilman, Robert H

2016-06-16

Taeniasis and cysticercosis are major causes of seizures and epilepsy. Infection by the causative parasite Taenia solium requires transmission between humans and pigs. The disease is considered to be eradicable, but data on attempts at regional elimination are lacking. We conducted a three-phase control program in Tumbes, Peru, to determine whether regional elimination would be feasible. We systematically tested and compared elimination strategies to show the feasibility of interrupting the transmission of T. solium infection in a region of highly endemic disease in Peru. In phase 1, we assessed the effectiveness and feasibility of six intervention strategies that involved screening of humans and pigs, antiparasitic treatment, prevention education, and pig replacement in 42 villages. In phase 2, we compared mass treatment with mass screening (each either with or without vaccination of pigs) in 17 villages. In phase 3, we implemented the final strategy of mass treatment of humans along with the mass treatment and vaccination of pigs in the entire rural region of Tumbes (107 villages comprising 81,170 people and 55,638 pigs). The effect of the intervention was measured after phases 2 and 3 with the use of detailed necropsy to detect pigs with live, nondegenerated cysts capable of causing new infection. The necropsy sampling was weighted in that we preferentially included more samples from seropositive pigs than from seronegative pigs. Only two of the strategies implemented in phase 1 resulted in limited control over the transmission of T. solium infection, which highlighted the need to intensify the subsequent strategies. After the strategies in phase 2 were implemented, no cyst that was capable of further transmission of T. solium infection was found among 658 sampled pigs. One year later, without further intervention, 7 of 310 sampled pigs had live, nondegenerated cysts, but no infected pig was found in 11 of 17 villages, including all the villages in which mass antiparasitic treatment plus vaccination was implemented. After the final strategy was implemented in phase 3, a total of 3 of 342 pigs had live, nondegenerated cysts, but no infected pig was found in 105 of 107 villages. We showed that the transmission of T. solium infection was interrupted on a regional scale in a highly endemic region in Peru. (Funded by the Bill and Melinda Gates Foundation and others.).

Converting science to policy through stakeholder involvement: an analysis of the European Marine Strategy Directive.

PubMed

Fletcher, Stephen

2007-12-01

The Marine Strategy Directive requires European Union Member States to develop science-based marine strategies with the involvement of stakeholders, in order that Europe's marine environment reaches 'good environmental status' by 2021. The scientific requirements of marine strategies are clearly defined within the Directive, however, the requirements related to stakeholder involvement are not. This paper presents a critical analysis of the provisions for stakeholder involvement with in the Marine Strategy Directive. In particular, the paper is focused upon the definition of stakeholder, the sequencing of involvement, and the form and purpose of involvement. The critique is set within an evaluative framework that considers policy-making to be a social process, rather than a purely scientific one. It is concluded that the Marine Strategy Directive lacks coherency with respect to stakeholder involvement which may perpetuate the traditional tension between marine science and policy. This in turn may compromise the ability of the Directive to protect Europe's marine environment.

Novel approaches to diagnosis and treatment of Juvenile Myelomonocytic Leukemia.

PubMed

Locatelli, Franco; Algeri, Mattia; Merli, Pietro; Strocchio, Luisa

2018-02-01

Juvenile myelomonocytic leukemia (JMML) is a clonal hematopoietic disorder of infancy/early childhood, resulting from oncogenic mutations in genes involved in the Ras pathway. As JMML often exhibits an aggressive course, the timing of diagnosis and treatment is critical to outcome. Areas covered: This review summarizes current approaches to diagnosis and treatment of JMML, highlighting most recent insights into genetic and epigenetic mechanisms underlying the disease, and providing an overview of novel potential therapeutic strategies. Expert commentary: At present, allogeneic HSCT remains the only potentially effective therapy, being able to cure more than 50% of patients, relapse representing the main cause of treatment failure. Prompt HSCT is recommended for all children with NF1, somatic PTPN11 and KRAS mutations, and for most children with somatic NRAS mutations. Conversely, a 'watch and wait' strategy should be adopted in children with germline CBL mutations, specific somatic NRAS mutation, and in Noonan syndrome patients, since spontaneous resolution has been reported to occur. Novel drugs targeting relevant nodes of JMML leukemogenesis have been explored in pre-HSCT window or at relapse. The use of 5-azacytidine, a DNA-hypomethylating agent reported to induce hematologic and molecular remission in some JMML children, is currently being investigated in clinical trials.

''Sandwich'' treatment for diospyrobezoar intestinal obstruction: A case report

PubMed Central

Zheng, Yi-Xiong; Prasoon, Pankaj; Chen, Yan; Hu, Liang; Chen, Li

2014-01-01

Intestinal obstruction is a common clinical entity encountered in surgical practice. The objective of this report is to corroborate an atypical scenario of intestinal obstruction in a Chinese patient and to focus on the diagnosis and treatment. A 27-year-old male presented with a history of gastric pain combined with nausea and abdominal distension that had been present for 5 d. The presence of a foreign body was detected by computed tomography and observed as an abnormal density within the stomach. A diospyrobezoar was revealed during gastroscopy, the extraction of which was prevented due to its size and firmness. An endoscopic holmium laser joined with a snare was used to fragment the obstruction, which was followed by management with a conservative “sandwich” treatment strategy involving intestinal decompression with an ileus tube and Coca-Cola lavage between endoscopic lithotripsy fragmentation procedures. This strategy resulted in the successful removal of the diospyrobezoar along with multiple small bowel obstructions. The patient was discharged after abatement of symptoms. The case presented here demonstrates the implementation of a conservative, yet successful, treatment as an alternative to conventional surgical removal of intestinal obstructions. PMID:25561823

Strategies that target leukocyte traffic in inflammatory bowel diseases: recent developments.

PubMed

Rivera-Nieves, Jesús

2015-11-01

We review the most recent developments regarding the targeting of molecules involved in the traffic of leukocytes for the treatment of inflammatory bowel diseases (IBD). We discuss the most important findings of one published phase II trial that targeted the β7 integrin (etrolizumab), two phase II trials that targeted the α4β7 integrin ligand: mucosal addressin cell adhesion molecule 1 (MAdCAM-1, PF-00547659), a phase II trial targeting the chemokine IP-10 (CXCL10) in Crohn's, and a phase II trial that targeted the sphingosine-1-phosphate receptor-1: ozanimod in patients with ulcerative colitis. Targeting molecules involved in leukocyte traffic has recently become an effective and well tolerated strategy for the treatment of IBD. Novel approaches now not only target the integrins on the lymphocyte surface, but also its endothelial ligand: MAdCAM-1. As with vedolizumab, antibodies against MAdCAM-1 appear most effective in ulcerative colitis rather than in Crohn's. Targeting chemokines or their receptors does not appear to have the same efficacy as those that target the most stable integrin: immunoglobulin superfamily interactions between the lymphocyte and endothelium. Preliminary results also suggest that the sphingosine-1-phosphate pathway might also be targeted therapeutically in IBD, no longer with parenterally administered antibodies but with orally administered small molecules.

Epoxyeicosatrienoic Acids Prevent Cisplatin-Induced Renal Apoptosis through a p38 Mitogen-Activated Protein Kinase–Regulated Mitochondrial Pathway

PubMed Central

Liu, Yingmei; Lu, Xiaodan; Nguyen, Sinh; Olson, Jean L.; Webb, Heather K.

2013-01-01

Soluble epoxide hydrolase (sEH) catalyzes the conversion of epoxyeicosatrienoic acids into less active eicosanoids, and inhibitors of sEH have anti-inflammatory and antiapoptotic properties. Based on previous observations that sEH inhibition attenuates cisplatin-induced nephrotoxicity by modulating nuclear factor-κB signaling, we hypothesized that this strategy would also attenuate cisplatin-induced renal apoptosis. Inhibition of sEH with AR9273 [1-adamantan-1-yl-3-(1-methylsulfonyl-piperidin-4-yl-urea)] reduced cisplatin-induced apoptosis through mechanisms involving mitochondrial apoptotic pathways and by reducing reactive oxygen species. Renal mitochondrial Bax induction following cisplatin treatment was significantly decreased by treatment of mice with AR9273 and these antiapoptotic effects involved p38 mitogen-activated protein kinase signaling. Similar mechanisms contributed to reduced apoptosis in Ephx2−/− mice treated with cisplatin. Moreover, in pig kidney proximal tubule cells, cisplatin-induced mitochondrial trafficking of Bax and cytochrome c, caspase-3 activation, and oxidative stress are significantly attenuated in the presence of epoxyeicosatrienoic acids (EETs). Collectively, these in vivo and in vitro studies demonstrate a role for EETs in limiting cisplatin-induced renal apoptosis. Inhibition of sEH represents a novel therapeutic strategy for protection against cisplatin-induced renal damage. PMID:24092818

Individualized cost-effective conventional ovulation induction treatment in normogonadotrophic anovulatory infertility (WHO group 2).

PubMed

Eijkemans, Marinus J C; Polinder, Suzanne; Mulders, Annemarie G M G J; Laven, Joop S E; Habbema, J Dik F; Fauser, Bart C J M

2005-10-01

Conventional treatment in normogonadotrophic anovulatory infertility (WHO 2) consists of clomiphene citrate (CC), followed by exogenous gonadotrophins (FSH) and IVF. Response to these treatments may be predicted on the basis of individual patient characteristics. We aimed to devise a patient-tailored, cost-effective treatment algorithm involving the above-mentioned treatment modalities, based on individual patient characteristics. Sixteen prognostic groups are defined, according to the presence or absence of: age >30 years, amenorrhea, elevated androgen levels and obesity. The chances of response with each of the three treatments were calculated using prediction models. Treatment costs were based on the data of 240 patients visiting a specialist academic fertility unit. Outcome was an ongoing pregnancy within 12 months after initiation of treatment. The costs per pregnancy of three different strategies were compared, with a threshold for cost-effectiveness of 10 000. The strategy CC + FSH + IVF compared with FSH + IVF generated more pregnancies against lower costs. Compared with CC + IVF, it also produced more pregnancies, but at higher costs. For <30 years of age with normal androgen levels, costs per pregnancy were less than 10 000. For women >30 years old, costs per pregnancy were 25 000 and over 200 000, when presenting with normal or elevated androgen levels, respectively. The conventional treatment protocol is efficient for women aged <30 years with normal androgen levels. For women >30 years old with elevated androgen levels, FSH may be skipped.

Surgical management of third nerve palsy

PubMed Central

Singh, Anupam; Bahuguna, Chirag; Nagpal, Ritu; Kumar, Barun

2016-01-01

Third nerve paralysis has been known to be associated with a wide spectrum of presentation and other associated factors such as the presence of ptosis, pupillary involvement, amblyopia, aberrant regeneration, poor bell's phenomenon, superior oblique (SO) overaction, and lateral rectus (LR) contracture. Correction of strabismus due to third nerve palsy can be complex as four out of the six extraocular muscles are involved and therefore should be approached differently. Third nerve palsy can be congenital or acquired. The common causes of isolated third nerve palsy in children are congenital (43%), trauma (20%), inflammation (13%), aneurysm (7%), and ophthalmoplegic migraine. Whereas, in adult population, common etiologies are vasculopathic disorders (diabetes mellitus, hypertension), aneurysm, and trauma. Treatment can be both nonsurgical and surgical. As nonsurgical modalities are not of much help, surgery remains the main-stay of treatment. Surgical strategies are different for complete and partial third nerve palsy. Surgery for complete third nerve palsy may involve supra-maximal recession - resection of the recti. This may be combined with SO transposition and augmented by surgery on the other eye. For partial third nerve, palsy surgery is determined according to nature and extent of involvement of extraocular muscles. PMID:27433033

Childhood cancer in El Salvador: A preliminary exploration of parental concerns in the abandonment of treatment.

PubMed

Rossell, Nuria; Gigengack, Roy; Blume, Stuart

2015-08-01

In El Salvador, children under 12 diagnosed with cancer have access to free treatment at a specialized national facility. Until recently, 13 percent of patients annually abandoned therapy--a serious loss of lives and scarce resources. This qualitative study explores how some parents perceived their child's cancer and treatment, and what led them to stop bringing their child for chemotherapy. In in-depth interviews, parents of six children who abandoned their child's cancer treatment discussed sickness and life circumstances during the course of treatment. Poverty, effects of treatment, mistrust, emotions and religious convictions all figured in the parents' explanation of their actions. However, each family weighed these concerns differently. It was the interaction of the concerns, and not the concern per se, that represented the explanatory frameworks the families used to explain stopping their child's treatment. This finding illustrates the parents' navigation among a collection of variable concerns, rather than exposing one fixed cause for their behavior. For example, poverty affects a parent's worldview as well as concrete living conditions, and therefore has a complex relationship with abandonment of treatment. Thus, it follows that strategies to reduce treatment abandonment (and increase a child's chance for survival) must be multidimensional. Qualitative studies of how families perceive childhood cancer and treatment can illuminate the processes and relationships involved in abandonment of treatment. This approach can also show how families' living circumstances frame their perceptions and inform strategies to improve how medical services are provided, thus reducing abandonment of treatment. Copyright © 2015 Elsevier Ltd. All rights reserved.

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.

Nanotechnology-based drug delivery systems for the treatment of Alzheimer’s disease

PubMed Central

Fonseca-Santos, Bruno; Gremião, Maria Palmira Daflon; Chorilli, Marlus

2015-01-01

Alzheimer’s disease is a neurological disorder that results in cognitive and behavioral impairment. Conventional treatment strategies, such as acetylcholinesterase inhibitor drugs, often fail due to their poor solubility, lower bioavailability, and ineffective ability to cross the blood–brain barrier. Nanotechnological treatment methods, which involve the design, characterization, production, and application of nanoscale drug delivery systems, have been employed to optimize therapeutics. These nanotechnologies include polymeric nanoparticles, solid lipid nanoparticles, nanostructured lipid carriers, microemulsion, nanoemulsion, and liquid crystals. Each of these are promising tools for the delivery of therapeutic devices to the brain via various routes of administration, particularly the intranasal route. The objective of this study is to present a systematic review of nanotechnology-based drug delivery systems for the treatment of Alzheimer’s disease. PMID:26345528

Uterine glands: development, function and experimental model systems

PubMed Central

Cooke, Paul S.; Spencer, Thomas E.; Bartol, Frank F.; Hayashi, Kanako

2013-01-01

Development of uterine glands (adenogenesis) in mammals typically begins during the early post-natal period and involves budding of nascent glands from the luminal epithelium and extensive cell proliferation in these structures as they grow into the surrounding stroma, elongate and mature. Uterine glands are essential for pregnancy, as demonstrated by the infertility that results from inhibiting the development of these glands through gene mutation or epigenetic strategies. Several genes, including forkhead box A2, beta-catenin and members of the Wnt and Hox gene families, are implicated in uterine gland development. Progestins inhibit uterine epithelial proliferation, and this has been employed as a strategy to develop a model in which progestin treatment of ewes for 8 weeks from birth produces infertile adults lacking uterine glands. More recently, mouse models have been developed in which neonatal progestin treatment was used to permanently inhibit adenogenesis and adult fertility. These studies revealed a narrow and well-defined window in which progestin treatments induced permanent infertility by impairing neonatal gland development and establishing endometrial changes that result in implantation defects. These model systems are being utilized to better understand the molecular mechanisms underlying uterine adenogenesis and endometrial function. The ability of neonatal progestin treatment in sheep and mice to produce infertility suggests that an approach of this kind may provide a contraceptive strategy with application in other species. Recent studies have defined the temporal patterns of adenogenesis in uteri of neonatal and juvenile dogs and work is underway to determine whether neonatal progestin or other steroid hormone treatments might be a viable contraceptive approach in this species. PMID:23619340

Teaching community program clinicians motivational interviewing using expert and train-the-trainer strategies.

PubMed

Martino, Steve; Ball, Samuel A; Nich, Charla; Canning-Ball, Monica; Rounsaville, Bruce J; Carroll, Kathleen M

2011-02-01

The effectiveness of expert-led (EX) and train-the-trainer (TT) strategies was compared to a self-study approach (SS) for teaching clinicians motivational interviewing (MI). Twelve community treatment programs were assigned randomly to the three conditions. EX and TT conditions used skill-building workshops and three monthly supervision sessions guided by treatment integrity ratings, performance feedback and coaching techniques. Trainers in TT were first trained and certified in MI and then prepared carefully to deliver the workshops and supervise MI at their programs. Clinicians in SS only received the training materials. Licensed out-patient and residential addiction and mental health treatment programs in the US state of Connecticut were involved in the study. Ninety-two clinicians who provided addiction treatment within these programs and had limited experience with MI participated in the study. Primary outcomes were the clinicians' MI adherence and competence and the percentage of clinicians meeting clinical trial standards of MI performance. Assessments occurred at baseline, post-workshop, post-supervision and at 12-week follow-up. The study found EX and TT, in comparison to SS, improved clinicians' adherence and competence significantly, with higher percentages of clinicians reaching clinical trial standards of MI performance and few differences between EX and TT. This study supports the combined use of workshops and supervision to teach community program clinicians MI and suggests the train-the-trainer approach may be a feasible and effective strategy for disseminating empirically supported treatments. © 2010 The Authors, Addiction © 2010 Society for the Study of Addiction.

Barriers to implementing evidence-based practices in addiction treatment programs: comparing staff reports on Motivational Interviewing, Adolescent Community Reinforcement Approach, Assertive Community Treatment, and Cognitive-behavioral Therapy.

PubMed

Amodeo, M; Lundgren, L; Cohen, A; Rose, D; Chassler, D; Beltrame, C; D'Ippolito, M

2011-11-01

This qualitative study explored barriers to implementing evidence-based practices (EBPs) in community-based addiction treatment organizations (CBOs) by comparing staff descriptions of barriers for four EBPs: Motivational Interviewing (MI), Adolescent Community Reinforcement Approach (A-CRA), Assertive Community Treatment (ACT), and Cognitive-behavioral Therapy (CBT). The CBOs received CSAT/SAMHSA funding from 2003 to 2008 to deliver services using EBPs. Phone interview responses from 172 CBO staff directly involved in EBP implementation were analyzed using content analysis, a method for making inferences and developing themes from the systematic review of participant narratives (Berelson, 1952). Staff described different types of barriers to implementing each EBP. For MI, the majority of barriers involved staff resistance or organizational setting. For A-CRA, the majority of barriers involved specific characteristics of the EBP or client resistance. For CBT, the majority of barriers were associated with client resistance, and for ACT, the majority of barriers were associated with resources. EBP designers, policy makers who support EBP dissemination and funders should include explicit strategies to address such barriers. Addiction programs proposing to use specific EBPs must consider whether their programs have the organizational capacity and community capacity to meet the demands of the EBP selected. Copyright © 2011 Elsevier Ltd. All rights reserved.

Systems Pharmacology Dissection of the Integrated Treatment for Cardiovascular and Gastrointestinal Disorders by Traditional Chinese Medicine

NASA Astrophysics Data System (ADS)

Zhang, Wenjuan; Tao, Qin; Guo, Zihu; Fu, Yingxue; Chen, Xuetong; Shar, Piar Ali; Shahen, Mohamed; Zhu, Jinglin; Xue, Jun; Bai, Yaofei; Wu, Ziyin; Wang, Zhenzhong; Xiao, Wei; Wang, Yonghua

2016-09-01

Though cardiovascular diseases (CVDs) and gastrointestinal disorders (GIDs) are different diseases associated with different organs, they are highly correlated clinically. Importantly, in Traditional Chinese Medicine (TCM), similar treatment strategies have been applied in both diseases. However, the etiological mechanisms underlying them remain unclear. Here, an integrated systems pharmacology approach is presented for illustrating the molecular correlations between CVDs and GIDs. Firstly, we identified pairs of genes that are associated with CVDs and GIDs and found that these genes are functionally related. Then, the association between 115 heart meridian (HM) herbs and 163 stomach meridian (SM) herbs and their combination application in Chinese patent medicine was investigated, implying that both CVDs and GIDs can be treated by the same strategy. Exemplified by a classical formula Sanhe Decoration (SHD) treating chronic gastritis, we applied systems-based analysis to introduce a drug-target-pathway-organ network that clarifies mechanisms of different diseases being treated by the same strategy. The results indicate that SHD regulated several pathological processes involved in both CVDs and GIDs. We experimentally confirmed the predictions implied by the effect of SHD for myocardial ischemia. The systems pharmacology suggests a novel integrated strategy for rational drug development for complex associated diseases.

Systems Pharmacology Dissection of the Integrated Treatment for Cardiovascular and Gastrointestinal Disorders by Traditional Chinese Medicine

PubMed Central

Zhang, Wenjuan; Tao, Qin; Guo, Zihu; Fu, Yingxue; Chen, Xuetong; Shar, Piar Ali; Shahen, Mohamed; Zhu, Jinglin; Xue, Jun; Bai, Yaofei; Wu, Ziyin; Wang, Zhenzhong; Xiao, Wei; Wang, Yonghua

2016-01-01

Though cardiovascular diseases (CVDs) and gastrointestinal disorders (GIDs) are different diseases associated with different organs, they are highly correlated clinically. Importantly, in Traditional Chinese Medicine (TCM), similar treatment strategies have been applied in both diseases. However, the etiological mechanisms underlying them remain unclear. Here, an integrated systems pharmacology approach is presented for illustrating the molecular correlations between CVDs and GIDs. Firstly, we identified pairs of genes that are associated with CVDs and GIDs and found that these genes are functionally related. Then, the association between 115 heart meridian (HM) herbs and 163 stomach meridian (SM) herbs and their combination application in Chinese patent medicine was investigated, implying that both CVDs and GIDs can be treated by the same strategy. Exemplified by a classical formula Sanhe Decoration (SHD) treating chronic gastritis, we applied systems-based analysis to introduce a drug-target-pathway-organ network that clarifies mechanisms of different diseases being treated by the same strategy. The results indicate that SHD regulated several pathological processes involved in both CVDs and GIDs. We experimentally confirmed the predictions implied by the effect of SHD for myocardial ischemia. The systems pharmacology suggests a novel integrated strategy for rational drug development for complex associated diseases. PMID:27597117

Leveraging the U.S. Criminal Justice System to Access Women for HIV Interventions.

PubMed

Meyer, Jaimie P; Muthulingam, Dharushana; El-Bassel, Nabila; Altice, Frederick L

2017-12-01

The criminal justice (CJ) system can be leveraged to access women for HIV prevention and treatment programs. Research is lacking on effective implementation strategies tailored to the specific needs of CJ-involved women. We conducted a scoping review of published studies in English from the United States that described HIV interventions, involved women or girls, and used the CJ system as an access point for sampling or intervention delivery. We identified 350 studies and synthesized data from 42 unique interventions, based in closed (n = 26), community (n = 7), or multiple/other CJ settings (n = 9). A minority of reviewed programs incorporated women-specific content or conducted gender-stratified analyses. CJ systems are comprised of diverse access points, each with unique strengths and challenges for implementing HIV treatment and prevention programs for women. Further study is warranted to develop women-specific and trauma-informed content and evaluate program effectiveness.

Clinical and Biochemical Manifestations of Depression: Relation to the Neurobiology of Stress

PubMed Central

Gold, Phillip W.; Machado-Vieira, Rodrigo; Pavlatou, Maria G.

2015-01-01

Major depressive disorder (MDD) is a chronic, recurrent, and severe psychiatric disorder with high mortality and medical comorbidities. Stress-related pathways have been directly involved in the pathophysiology and treatment of MDD. The present paper provides an overview on the stress system as a model to understand key pathophysiological paradigms in MDD. These mechanisms involve behavioral, cognitive, and systemic manifestations and are also associated with the mechanisms of action of effective antidepressants. Aspects such as depression subtypes, inflammation, insulin resistance, oxidative stress, and prothrombotic states in critical brain circuits and periphery are critically appraised. Finally, new strategies for approaching treatment-resistant major depression and potential adverse effects associated with this complex and intricate network are highlighted. The authors used PubMed as the database for this review. Each author extracted relevant data and assessed the methodological quality of each study. PMID:25878903

Indications and limitations of chemotherapy and targeted agents in non-small cell lung cancer brain metastases.

PubMed

Zimmermann, Stefan; Dziadziuszko, Rafal; Peters, Solange

2014-07-01

Lung cancer is characterized by the highest incidence of solid tumor-related brain metastases, which are reported with a growing incidence during the last decade. Prognostic assessment may help to identify subgroups of patients that could benefit from more aggressive therapy of metastatic disease, in particular when central nervous system is involved. The recent sub-classification of non-small cell lung cancer (NSCLC) into molecularly-defined "oncogene-addicted" tumors, the emergence of effective targeted treatments in molecularly defined patient subsets, global improvement of advanced NSCLC survival as well as the availability of refined new radiotherapy techniques are likely to impact on outcomes of patients with brain dissemination. The present review focuses on key evidence and research strategies for systemic treatment of patients with central nervous system involvement in non-small cell lung cancer. Copyright © 2014 Elsevier Ltd. All rights reserved.

Cannabinoids and Dementia: A Review of Clinical and Preclinical Data

PubMed Central

Walther, Sebastian; Halpern, Michael

2010-01-01

The endocannabinoid system has been shown to be associated with neurodegenerative diseases and dementia. We review the preclinical and clinical data on cannabinoids and four neurodegenerative diseases: Alzheimer’s disease (AD), Huntington’s disease (HD), Parkinson’s disease (PD) and vascular dementia (VD). Numerous studies have demonstrated an involvement of the cannabinoid system in neurotransmission, neuropathology and neurobiology of dementias. In addition, several candidate compounds have demonstrated efficacy in vitro. However, some of the substances produced inconclusive results in vivo. Therefore, only few trials have aimed to replicate the effects seen in animal studies in patients. Indeed, the literature on cannabinoid administration in patients is scarce. While preclinical findings suggest causal treatment strategies involving cannabinoids, clinical trials have only assessed the suitability of cannabinoid receptor agonists, antagonists and cannabidiol for the symptomatic treatment of dementia. Further research is needed, including in vivo models of dementia and human studies. PMID:27713372

Mucosal melanoma of the upper airways tract mucosal melanoma: A systematic review with meta-analyses of treatment.

PubMed

Jarrom, David; Paleri, Vinidh; Kerawala, Cyrus; Roques, Thomas; Bhide, Shreerang; Newman, Laurence; Winter, Stuart C

2017-04-01

Mucosal melanoma of the upper aerodigestive tract (MM-UADT) occurs in a complex anatomic region. It represents a small number of tumors of the head and neck and a small number of melanoma cases. Search strategies initially identified 600, 11 of which were included in this study. All studies involved surgery and radiotherapy. None were randomized, and all were assessed as having a high risk of selection and performance bias. No studies reported quality of life, treatment-related mortality, or morbidity. The results indicate that the addition of radiotherapy to surgery reduces the rate of locoregional recurrence (hazard ratio [HR], 0.60; 95% confidence interval [CI], 0.42-0.87). There was no statistically significant difference in overall survival (HR, 1.16; 95% CI, 0.98-1.37). Surgical resection with postoperative radiotherapy remains the optimal treatment strategy for locoregional control. More robust studies and the use of molecular targeted therapies need to be undertaken to improve overall survival. © 2016 Wiley Periodicals, Inc. Head Neck 39: 819-825, 2017. © 2016 Wiley Periodicals, Inc.

MAP3K8/TPL-2/COT is a potential predictive marker for MEK inhibitor treatment in high-grade serous ovarian carcinomas.

PubMed

Gruosso, Tina; Garnier, Camille; Abelanet, Sophie; Kieffer, Yann; Lemesre, Vincent; Bellanger, Dorine; Bieche, Ivan; Marangoni, Elisabetta; Sastre-Garau, Xavier; Mieulet, Virginie; Mechta-Grigoriou, Fatima

2015-10-12

Ovarian cancer is a silent disease with a poor prognosis that urgently requires new therapeutic strategies. In low-grade ovarian tumours, mutations in the MAP3K BRAF gene constitutively activate the downstream kinase MEK. Here we demonstrate that an additional MAP3K, MAP3K8 (TPL-2/COT), accumulates in high-grade serous ovarian carcinomas (HGSCs) and is a potential prognostic marker for these tumours. By combining analyses on HGSC patient cohorts, ovarian cancer cells and patient-derived xenografts, we demonstrate that MAP3K8 controls cancer cell proliferation and migration by regulating key players in G1/S transition and adhesion dynamics. In addition, we show that the MEK pathway is the main pathway involved in mediating MAP3K8 function, and that MAP3K8 exhibits a reliable predictive value for the effectiveness of MEK inhibitor treatment. Our data highlight key roles for MAP3K8 in HGSC and indicate that MEK inhibitors could be a useful treatment strategy, in combination with conventional chemotherapy, for this disease.

When sepsis persists: a review of MRSA bacteraemia salvage therapy.

PubMed

Kullar, Ravina; Sakoulas, George; Deresinski, Stan; van Hal, Sebastiaan J

2016-03-01

MRSA bacteraemia (MRSAB), including infective endocarditis, carries a high mortality rate, with up to 50% of patients failing initial therapy with vancomycin and requiring salvage therapy. Persistent MRSAB can be difficult to successfully eliminate, especially when source control is not possible due to an irremovable focus or the bacteraemia still persists despite surgical intervention. Although vancomycin and daptomycin are the only two antibiotics approved by the US FDA for the treatment of patients with MRSAB as monotherapy, the employment of novel strategies is required to effectively treat patients with persistent MRSAB and these may frequently involve combination drug therapy. Treatment strategies that are reviewed in this manuscript include vancomycin combined with a β-lactam, daptomycin-based therapy, ceftaroline-based therapy, linezolid-based therapy, quinupristin/dalfopristin, telavancin, trimethoprim/sulfamethoxazole-based therapy and fosfomycin-based therapy. We recommend that combination antibiotic therapy be considered for use in MRSAB salvage treatment. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

A novel drug-free strategy of nano-pulse stimulation sequence (NPSS) in oral cancer therapy: In vitro and in vivo study.

PubMed

Guo, Jinsong; Dong, Feihong; Ding, Lian; Wang, Kaile; Zhang, Jue; Fang, Jing

2018-04-19

Nano-pulse stimulation (NPS) is a novel technology to induce cancer apoptosis. In this study, based on the energy-dose effect of NPS, we designed a special NPS sequence (NPSS) with low field intensity. The effectiveness and mechanisms of NPSS on oral cancer therapy were evaluated by cell proliferation assays, microscopic investigation, JC-1 mitochondrial membrane potential assay, tumor inhibition assays, immunohistochemistry (IHC) assay, Ca 2+ , NOS and ROS detection assays, respectively. The results demonstrated that NPSS treatment significantly inhibited oral cancer growth in vitro and in vivo. Furthermore, we found that NPSS treatment induced an obviously apoptosis and mitochondrial membrane potential (ΔΨm) reduction in Cal-27 cells. Notably, further experiments revealed that the mechanisms of crosstalk signaling between NO, ROS and Ca 2+ involvement in NPSS treatment. In conclusion, this is a proof-of-concept study that provides a potential alternative strategy for developing and applying NPSS in oral cancer therapy. Copyright © 2018 Elsevier B.V. All rights reserved.

Acute graft-versus-host disease: a bench-to-bedside update.

PubMed

Holtan, Shernan G; Pasquini, Marcelo; Weisdorf, Daniel J

2014-07-17

Over the past 5 years, many novel approaches to early diagnosis, prevention, and treatment of acute graft-versus-host disease (aGVHD) have been translated from the bench to the bedside. In this review, we highlight recent discoveries in the context of current aGVHD care. The most significant innovations that have already reached the clinic are prophylaxis strategies based upon a refinement of our understanding of key sensors, effectors, suppressors of the immune alloreactive response, and the resultant tissue damage from the aGVHD inflammatory cascade. In the near future, aGVHD prevention and treatment will likely involve multiple modalities, including small molecules regulating immunologic checkpoints, enhancement of suppressor cytokines and cellular subsets, modulation of the microbiota, graft manipulation, and other donor-based prophylaxis strategies. Despite long-term efforts, major challenges in treatment of established aGVHD still remain. Resolution of inflammation and facilitation of rapid immune reconstitution in those with only a limited response to corticosteroids is a research arena that remains rife with opportunity and urgent clinical need. © 2014 by The American Society of Hematology.

Predictive modelling of a novel anti-adhesion therapy to combat bacterial colonisation of burn wounds

PubMed Central

Huebinger, Ryan M.; Keen, Emma

2018-01-01

As the development of new classes of antibiotics slows, bacterial resistance to existing antibiotics is becoming an increasing problem. A potential solution is to develop treatment strategies with an alternative mode of action. We consider one such strategy: anti-adhesion therapy. Whereas antibiotics act directly upon bacteria, either killing them or inhibiting their growth, anti-adhesion therapy impedes the binding of bacteria to host cells. This prevents bacteria from deploying their arsenal of virulence mechanisms, while simultaneously rendering them more susceptible to natural and artificial clearance. In this paper, we consider a particular form of anti-adhesion therapy, involving biomimetic multivalent adhesion molecule 7 coupled polystyrene microbeads, which competitively inhibit the binding of bacteria to host cells. We develop a mathematical model, formulated as a system of ordinary differential equations, to describe inhibitor treatment of a Pseudomonas aeruginosa burn wound infection in the rat. Benchmarking our model against in vivo data from an ongoing experimental programme, we use the model to explain bacteria population dynamics and to predict the efficacy of a range of treatment strategies, with the aim of improving treatment outcome. The model consists of two physical compartments: the host cells and the exudate. It is found that, when effective in reducing the bacterial burden, inhibitor treatment operates both by preventing bacteria from binding to the host cells and by reducing the flux of daughter cells from the host cells into the exudate. Our model predicts that inhibitor treatment cannot eliminate the bacterial burden when used in isolation; however, when combined with regular or continuous debridement of the exudate, elimination is theoretically possible. Lastly, we present ways to improve therapeutic efficacy, as predicted by our mathematical model. PMID:29723210

[Cervix cancer].

PubMed

Pointreau, Y; Ruffier Loubière, A; Denis, F; Barillot, I

2010-11-01

Cervix cancers declined in most developed countries in recent years, but remain, the third worldwide leading cause of cancer death in women. A precise staging, based on clinical exam, an abdominal and pelvic MRI, a possible PET-CT and a possible lymph node sampling is necessary to adapt the best therapeutic strategy. In France, the treatments of tumors of less than 4 cm without nodal involvement are often based on radiotherapy followed by surgery and, whereas tumors larger than 4 cm and involved nodes are treated with concurrent chemoradiotherapy. Based on an illustrated clinical case, indications, delineation, dosimetry and complications expected with radiotherapy are demonstrated. Copyright © 2010 Elsevier Masson SAS. All rights reserved.

Plastic Biliary Stent Occlusion: Factors Involved and Possible Preventive Approaches

PubMed Central

Donelli, Gianfranco; Guaglianone, Emilio; Di Rosa, Roberta; Fiocca, Fausto; Basoli, Antonio

2007-01-01

Endoscopic biliary stenting is today the most common palliative treatment for patients suffering from obstructive jaundice associated with malignant hepatobiliary tumors or benign strictures. However, recurrent jaundice, with or without cholangitis, is a major complication of a biliary endoprosthesis insertion. Thus, stent removal and replacement with a new one frequently occurs as a consequence of device blockage caused by microbial biofilm growth and biliary sludge accumulation in the lumen. Factors and mechanisms involved in plastic stent clogging arising from epidemiological, clinical and experimental data, as well as the possible strategies to prevent biliary stent failure, will be reviewed and discussed. PMID:17456835

Control of Taenia solium taeniasis/cysticercosis: The best way forward for sub-Saharan Africa?

PubMed

Gabriël, S; Dorny, P; Mwape, K E; Trevisan, C; Braae, U C; Magnussen, P; Thys, S; Bulaya, C; Phiri, I K; Sikasunge, C S; Makungu, C; Afonso, S; Nicolau, Q; Johansen, M V

2017-01-01

Taenia solium taeniasis/cysticercosis is a neglected parasitic zoonosis with significant economic and public health impacts. Control measures can be broadly grouped into community health education, improvements in hygiene and sanitary conditions, proper meat handling at household and community level, improved standards of meat inspection, pig management, treatment of individual patients and possibly human populations, and treatment and/or vaccination of porcine populations. This manuscript looks critically into currently existing control options and provides suggestions on which (combination of) tools would be most effective in the control of T. solium taeniasis/cysticercosis in sub-Saharan Africa. Field data and disease transmission simulations suggest that implementation of a single intervention control strategy will not lead to a satisfactory reduction of disease morbidity or transmission. A feasible strategy to combat T. solium taeniasis/cysticercosis would include a combination of approaches focussing on both human (health education and treatment) and animal host (management, treatment and vaccination), which can vary for different communities and different geographical locations. Selection of the specific strategy depends on cost-effectiveness analyses based on solid field data, currently unavailable, though urgently needed; as well as on health priorities and resources of the country. A One Health approach involving medical, veterinary, environmental and social sectors is essential for T. solium to be controlled and eventually eliminated. Finally the success of any intervention is largely dependent on the level of societal and political acceptance, commitment and engagement. Copyright © 2016 Elsevier B.V. All rights reserved.

Survival Benefits of Invasive Versus Conservative Strategies in Heart Failure in Patients With Reduced Ejection Fraction and Coronary Artery Disease: A Meta-Analysis.

PubMed

Wolff, Georg; Dimitroulis, Dimitrios; Andreotti, Felicita; Kołodziejczak, Michalina; Jung, Christian; Scicchitano, Pietro; Devito, Fiorella; Zito, Annapaola; Occhipinti, Michele; Castiglioni, Battistina; Calveri, Giuseppe; Maisano, Francesco; Ciccone, Marco M; De Servi, Stefano; Navarese, Eliano P

2017-01-01

Heart failure with reduced ejection fraction caused by ischemic heart disease is associated with increased morbidity and mortality. It remains unclear whether revascularization by either coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI) carries benefits or risks in this group of stable patients compared with medical treatment. We performed a meta-analysis of available studies comparing different methods of revascularization (PCI or CABG) against each other or medical treatment in patients with coronary artery disease and left ventricular ejection fraction ≤40%. The primary outcome was all-cause mortality; myocardial infarction, revascularization, and stroke were also analyzed. Twenty-one studies involving a total of 16 191 patients were included. Compared with medical treatment, there was a significant mortality reduction with CABG (hazard ratio, 0.66; 95% confidence interval, 0.61-0.72; P<0.001) and PCI (hazard ratio, 0.73; 95% confidence interval, 0.62-0.85; P<0.001). When compared with PCI, CABG still showed a survival benefit (hazard ratio, 0.82; 95% confidence interval, 0.75-0.90; P<0.001). The present meta-analysis indicates that revascularization strategies are superior to medical treatment in improving survival in patients with ischemic heart disease and reduced ejection fraction. Between the 2 revascularization strategies, CABG seems more favorable compared with PCI in this particular clinical setting. © 2017 American Heart Association, Inc.

Multiple stakeholders in multi-criteria decision-making in the context of Municipal Solid Waste Management: A review.

PubMed

Soltani, Atousa; Hewage, Kasun; Reza, Bahareh; Sadiq, Rehan

2015-01-01

Municipal Solid Waste Management (MSWM) is a complicated process that involves multiple environmental and socio-economic criteria. Decision-makers look for decision support frameworks that can guide in defining alternatives, relevant criteria and their weights, and finding a suitable solution. In addition, decision-making in MSWM problems such as finding proper waste treatment locations or strategies often requires multiple stakeholders such as government, municipalities, industries, experts, and/or general public to get involved. Multi-criteria Decision Analysis (MCDA) is the most popular framework employed in previous studies on MSWM; MCDA methods help multiple stakeholders evaluate the often conflicting criteria, communicate their different preferences, and rank or prioritize MSWM strategies to finally agree on some elements of these strategies and make an applicable decision. This paper reviews and brings together research on the application of MCDA for solving MSWM problems with more focus on the studies that have considered multiple stakeholders and offers solutions for such problems. Results of this study show that AHP is the most common approach in consideration of multiple stakeholders and experts and governments/municipalities are the most common participants in these studies. Copyright © 2014 Elsevier Ltd. All rights reserved.

CORTICOSTEROIDS AND MUSCLE WASTING ROLE OF TRANSCRIPTION FACTORS, NUCLEAR COFACTORS, AND HYPERACETYLATION

PubMed Central

Hasselgren, Per-Olof; Alamdari, Nima; Aversa, Zaira; Gonnella, Patricia; Smith, Ira J; Tizio, Steven

2010-01-01

Purpose of review The purpose of this review is to discuss novel insight into mechanisms of glucocorticoid-regulated muscle wasting, in particular the role of transcription factors and nuclear cofactors. In addition, novel strategies that may become useful in the treatment or prevention of glucocorticoid-induced muscle wasting are reviewed. Recent findings Studies suggest that glucocorticoid-induced upregulation of the transcription factors FOXO1 and C/EBPβ and downregulation of MyoD and myogenin are involved in glucocorticoid-induced muscle wasting. In addition, glucocorticoid-induced hyperacetylation caused by increased expression of the nuclear cofactor p300 and its histone acetyl transferase activity and decreased expression and activity of histone deacetylases (HDACs) plays an important role in glucocorticoid-induced muscle proteolysis and wasting. Other mechanisms may also be involved in glucocorticoid-induced muscle wasting, including insulin resistance and store-operated calcium entry. Novel potential strategies to prevent or treat glucocorticoid-induced muscle wasting include the use of small molecule HDAC activators, dissociated glucocorticoid receptor agonists, and 11β-hydroxysteroid dehydrogenase type 1 inhibitors. Summary An increased understanding of molecular mechanisms regulating glucocorticoid-induced muscle wasting will help develop new strategies to prevent and treat this debilitating condition. PMID:20473154

Role of Genetics in the Etiology of Autistic Spectrum Disorder: Towards a Hierarchical Diagnostic Strategy

PubMed Central

Robert, Cyrille; Pasquier, Laurent; Cohen, David; Fradin, Mélanie; Canitano, Roberto; Damaj, Léna; Odent, Sylvie; Tordjman, Sylvie

2017-01-01

Progress in epidemiological, molecular and clinical genetics with the development of new techniques has improved knowledge on genetic syndromes associated with autism spectrum disorder (ASD). The objective of this article is to show the diversity of genetic disorders associated with ASD (based on an extensive review of single-gene disorders, copy number variants, and other chromosomal disorders), and consequently to propose a hierarchical diagnostic strategy with a stepwise evaluation, helping general practitioners/pediatricians and child psychiatrists to collaborate with geneticists and neuropediatricians, in order to search for genetic disorders associated with ASD. The first step is a clinical investigation involving: (i) a child psychiatric and psychological evaluation confirming autism diagnosis from different observational sources and assessing autism severity; (ii) a neuropediatric evaluation examining neurological symptoms and developmental milestones; and (iii) a genetic evaluation searching for dysmorphic features and malformations. The second step involves laboratory and if necessary neuroimaging and EEG studies oriented by clinical results based on clinical genetic and neuropediatric examinations. The identification of genetic disorders associated with ASD has practical implications for diagnostic strategies, early detection or prevention of co-morbidity, specific treatment and follow up, and genetic counseling. PMID:28287497

Role of Genetics in the Etiology of Autistic Spectrum Disorder: Towards a Hierarchical Diagnostic Strategy.

PubMed

Robert, Cyrille; Pasquier, Laurent; Cohen, David; Fradin, Mélanie; Canitano, Roberto; Damaj, Léna; Odent, Sylvie; Tordjman, Sylvie

2017-03-12

Progress in epidemiological, molecular and clinical genetics with the development of new techniques has improved knowledge on genetic syndromes associated with autism spectrum disorder (ASD). The objective of this article is to show the diversity of genetic disorders associated with ASD (based on an extensive review of single-gene disorders, copy number variants, and other chromosomal disorders), and consequently to propose a hierarchical diagnostic strategy with a stepwise evaluation, helping general practitioners/pediatricians and child psychiatrists to collaborate with geneticists and neuropediatricians, in order to search for genetic disorders associated with ASD. The first step is a clinical investigation involving: (i) a child psychiatric and psychological evaluation confirming autism diagnosis from different observational sources and assessing autism severity; (ii) a neuropediatric evaluation examining neurological symptoms and developmental milestones; and (iii) a genetic evaluation searching for dysmorphic features and malformations. The second step involves laboratory and if necessary neuroimaging and EEG studies oriented by clinical results based on clinical genetic and neuropediatric examinations. The identification of genetic disorders associated with ASD has practical implications for diagnostic strategies, early detection or prevention of co-morbidity, specific treatment and follow up, and genetic counseling.

Cost-Utility Analysis of Screening Strategies for Diabetic Retinopathy in Korea.

PubMed

Kim, Sang-Won; Kang, Gil-Won

2015-12-01

This study involved a cost-utility analysis of early diagnosis and treatment of diabetic retinopathy depending on the screening strategy used. The four screening strategies evaluated were no screening, opportunistic examination, systematic fundus photography, and systematic examination by an ophthalmologists. Each strategy was evaluated in 10,000 adults aged 40 yr with newly diagnosed diabetes mellitus (hypothetical cohort). The cost of each strategy was estimated in the perspective of both payer and health care system. The utility was estimated using quality-adjusted life years (QALY). Incremental Cost Effectiveness Ratio (ICER) for the different screening strategies was analyzed. After exclusion of the weakly dominating opportunistic strategy, the ICER of systematic photography was 57,716,867 and that of systematic examination by ophthalmologists was 419,989,046 from the perspective of the healthcare system. According to the results, the systematic strategy is preferable to the opportunistic strategy from the perspective of both a payer and a healthcare system. Although systematic examination by ophthalmologists may have higher utility than systematic photography, it is associated with higher cost. The systematic photography is the best strategy in terms of cost-utility. However systematic examination by ophthalmologists can also be a suitable policy alternative, if the incremental cost is socially acceptable.

Effects of the GluN2B-NMDA receptor antagonist Ro 25-6981 on two types of behavioral flexibility in rats.

PubMed

Clark, Emma; Antoniak, Kristen; Feniquito, Alyssandra; Dringenberg, Hans C

2017-02-15

Recent evidence has implicated N-methyl-d-aspartate receptors (NMDARs) in several aspects of learning and behavioral flexibility in rodents. Here, we examined the effects of treatment with Ro 25-6981, a selective antagonist of NMDARs containing GluN2B subunits, on two types of behavioral flexibility in rats, spatial reversal learning and set-shifting (spatial vs. motor strategy). To examine spatial reversal learning, rats were trained to swim to a hidden platform in a water maze over four days. On the following day, the platform was moved to a new location in the maze. Administration of Ro 25-6981 (10mg/kg) selectively impaired the early phase of reversal learning, but all rats learned to navigate to the new platform location over 12 trials. To examine set-shifting, independent groups of rats were trained to either swim to a fixed location (spatial strategy) or use a motor response (e.g., "turn left"; motor strategy) to find a hidden escape platform in a cross-shaped water maze apparatus; after task acquisition, rats were trained on the second, novel strategy (set-shift) following treatment with either Ro 25-6981 (10mg/kg) or saline. Administration of Ro 25-6981 had no effect on the ability of rats to perform the set-shift and use the new strategy to locate the escape platform. These results suggest that, in rats, spatial reversal learning, but not set-shifting, is sensitive to Ro-25-6981 treatment. Thus, NMDARs-GluN2B signaling may play a selective role in some forms of behavioral plasticity, particularly for situations involving the updating of information in the spatial domain. Copyright © 2016 Elsevier B.V. All rights reserved.

Anthelmintic resistance in equine nematodes

PubMed Central

Matthews, Jacqueline B.

2014-01-01

Anthelmintics have been applied indiscriminately to control horse nematodes for over 40 years. Three broad-spectrum anthelmintic classes are currently registered for nematode control in horses: benzimidazoles (fenbendazole, oxibendazole), tetrahydropyrimidines (pyrantel) and macrocyclic lactones (ivermectin, moxidectin). Generally, control strategies have focused on nematode egg suppression regimens that involve the frequent application of anthelmintics to all horses at intervals based on strongyle egg reappearance periods after treatment. The widespread use of such programmes has substantially reduced clinical disease, especially that associated with large strongyle species; however, high treatment frequency has led to considerable selection pressure for anthelmintic resistance, particularly in cyathostomin species. Field studies published over the last decade indicate that benzimidazole resistance is widespread globally in cyathostomins and there are also many reports of resistance to pyrantel in these worms. Cyathostomin resistance to macrocyclic lactone compounds is emerging, principally measured as a reduction in strongyle egg reappearance time observed after treatment. Ivermectin resistance is a further concern in the small intestinal nematode, Parascaris equorum, an important pathogen of foals. These issues indicate that horse nematodes must now be controlled using methods less dependent on anthelmintic use and more reliant on management practices designed to reduce the force of infection in the environment. Such strategies include improved grazing management integrated with targeted anthelmintic administration involving faecal egg count (FEC)-directed treatments. The latter require that the supporting diagnostic tests available are robust and practically applicable. Recent research has focused on maximising the value of FEC analysis in horses and on optimizing protocols for anthelmintic efficacy testing. Other studies have sought to develop diagnostics that will help define levels of pre-patent infection. This review describes recent advances in each of these areas of research. PMID:25516842

Optimizing Tactics for Use of the U.S. Antiviral Strategic National Stockpile for Pandemic Influenza

PubMed Central

Dimitrov, Nedialko B.; Goll, Sebastian; Hupert, Nathaniel; Pourbohloul, Babak; Meyers, Lauren Ancel

2011-01-01

In 2009, public health agencies across the globe worked to mitigate the impact of the swine-origin influenza A (pH1N1) virus. These efforts included intensified surveillance, social distancing, hygiene measures, and the targeted use of antiviral medications to prevent infection (prophylaxis). In addition, aggressive antiviral treatment was recommended for certain patient subgroups to reduce the severity and duration of symptoms. To assist States and other localities meet these needs, the U.S. Government distributed a quarter of the antiviral medications in the Strategic National Stockpile within weeks of the pandemic's start. However, there are no quantitative models guiding the geo-temporal distribution of the remainder of the Stockpile in relation to pandemic spread or severity. We present a tactical optimization model for distributing this stockpile for treatment of infected cases during the early stages of a pandemic like 2009 pH1N1, prior to the wide availability of a strain-specific vaccine. Our optimization method efficiently searches large sets of intervention strategies applied to a stochastic network model of pandemic influenza transmission within and among U.S. cities. The resulting optimized strategies depend on the transmissability of the virus and postulated rates of antiviral uptake and wastage (through misallocation or loss). Our results suggest that an aggressive community-based antiviral treatment strategy involving early, widespread, pro-rata distribution of antivirals to States can contribute to slowing the transmission of mildly transmissible strains, like pH1N1. For more highly transmissible strains, outcomes of antiviral use are more heavily impacted by choice of distribution intervals, quantities per shipment, and timing of shipments in relation to pandemic spread. This study supports previous modeling results suggesting that appropriate antiviral treatment may be an effective mitigation strategy during the early stages of future influenza pandemics, increasing the need for systematic efforts to optimize distribution strategies and provide tactical guidance for public health policy-makers. PMID:21283514

Ultraviolet Phototherapy Management of Moderate-to-Severe Plaque Psoriasis: An Evidence-Based Analysis.

PubMed

2009-01-01

The purpose of this evidence based analysis was to determine the effectiveness and safety of ultraviolet phototherapy for moderate-to-severe plaque psoriasis. The specific research questions for the evidence review were as follows: What is the safety of ultraviolet phototherapy for moderate-to-severe plaque psoriasis?What is the effectiveness of ultraviolet phototherapy for moderate-to-severe plaque psoriasis? TARGET POPULATION AND CONDITION Psoriasis is a common chronic, systemic inflammatory disease affecting the skin, nails and occasionally the joints and has a lifelong waning and waxing course. It has a worldwide occurrence with a prevalence of at least 2% of the general population, making it one of the most common systemic inflammatory diseases. The immune-mediated disease has several clinical presentations with the most common (85% - 90%) being plaque psoriasis. Characteristic features of psoriasis include scaling, redness, and elevation of the skin. Patients with psoriasis may also present with a range of disabling symptoms such as pruritus (itching), pain, bleeding, or burning associated with plaque lesions and up to 30% are classified as having moderate-to-severe disease. Further, some psoriasis patients can be complex medical cases in which diabetes, inflammatory bowel disease, and hypertension are more likely to be present than in control populations and 10% also suffer from arthritis (psoriatic arthritis). The etiology of psoriasis is unknown but is thought to result from complex interactions between the environment and predisposing genes. Management of psoriasis is related to the extent of the skin involvement, although its presence on the hands, feet, face or genitalia can present challenges. Moderate-to-severe psoriasis is managed by phototherapy and a range of systemic agents including traditional immunosuppressants such as methotrexate and cyclospsorin. Treatment with modern immunosuppressant agents known as biologicals, which more specifically target the immune defects of the disease, is usually reserved for patients with contraindications and those failing or unresponsive to treatments with traditional immunosuppressants or phototherapy. Treatment plans are based on a long-term approach to managing the disease, patient's expectations, individual responses and risk of complications. The treatment goals are several fold but primarily to: 1) improve physical signs and secondary psychological effects,2) reduce inflammation and control skin shedding,3) control physical signs as long as possible, and to4) avoid factors that can aggravate the condition.Approaches are generally individualized because of the variable presentation, quality of life implications, co-existent medical conditions, and triggering factors (e.g. stress, infections and medications). Individual responses and commitments to therapy also present possible limitations. PHOTOTHERAPY: Ultraviolet phototherapy units have been licensed since February 1993 as a class 2 device in Canada. Units are available as hand held devices, hand and foot devices, full-body panel, and booth styles for institutional and home use. Units are also available with a range of ultraviolet A, broad and narrow band ultraviolet B (BB-UVB and NB-UVB) lamps. After establishing appropriate ultraviolet doses, three-times weekly treatment schedules for 20 to 25 treatments are generally needed to control symptoms. The literature search strategy employed keywords and subject headings to capture the concepts of 1) phototherapy and 2) psoriasis. The search involved runs in the following databases: Ovid MEDLINE (1996 to March Week 3 2009), OVID MEDLINE In-Process and Other Non-Indexed Citations, EMBASE (1980 to 2009 Week 13), the Wiley Cochrane Library, and the Centre for Reviews and Dissemination/International Agency for Health Technology Assessment. Parallel search strategies were developed for the remaining databases. Search results were limited to human and English-language published between January 1999 and March 31, 2009. Search alerts were generated and reviewed for relevant literature up until May 31, 2009. Inclusion CriteriaExclusion CriteriaEnglish language reports and human studiesUltraviolet phototherapy interventions for plaque-type psoriasisReports involving efficacy and/or safety outcome studiesOriginal reports with defined study methodologyStandardized measurements on outcome events such as technical success, safety, effectiveness, durability, quality of life or patient satisfactionNon-systematic reviews, letters, comments and editorialsRandomized trials involving side-to-side or half body comparisonsRandomized trials not involving ultraviolet phototherapy intervention for plaque-type psoriasisTrials involving dosing studies, pilot feasibility studies or lacking control groups A 2000 health technology evidence report on the overall management of psoriasis by The National Institute Health Research (NIHR) Health Technology Assessment Program of the UK was identified in the MAS evidence-based review. The report included 109 RCT studies published between 1966 and June 1999 involving four major treatment approaches - 51 on phototherapy, 32 on oral retinoids, 18 on cyclosporin and five on fumarates.. The absence of RCTs on methotrexate was noted as original studies with this agent had been performed prior to 1966. Of the 51 RCT studies involving phototherapy, 22 involved UVA, 21 involved UVB, five involved both UVA and UVB and three involved natural light as a source of UV. The RCT studies included comparisons of treatment schedules, ultraviolet source, addition of adjuvant therapies, and comparisons between phototherapy and topical treatment schedules. Because of heterogeneity, no synthesis or meta-analysis could be performed. Overall, the reviewers concluded that the efficacy of only five therapies could be supported from the RCT-based evidence review: photochemotherapy or phototherapy, cyclosporin, systemic retinoids, combination topical vitamin D(3) analogues (calcipotriol) and corticosteroids in combination with phototherapy and fumarates. Although there was no RCT evidence supporting methotrexate, it's efficacy for psoriasis is well known and it continues to be a treatment mainstay. The conclusion of the NIHR evidence review was that both photochemotherapy and phototherapy were effective treatments for clearing psoriasis, although their comparative effectiveness was unknown. Despite the conclusions on efficacy, a number of issues were identified in the evidence review and several areas for future research were discussed to address these limitations. Trials focusing on comparative effectiveness, either between ultraviolet sources or between classes of treatment such as methotrexate versus phototherapy, were recommended to refine treatment algorithms. The need for better assessment of cost-effectiveness of therapies to consider systemic drug costs and costs of surveillance, as well as drug efficacy, were also noted. Overall, the authors concluded that phototherapy and photochemotherapy had important roles in psoriasis management and were standard therapeutic options for psoriasis offered in dermatology practices. The MAS evidence-based review focusing on the RCT trial evidence for ultraviolet phototherapy management of moderate-to-severe plaque psoriasis was performed as an update to the NIHR 2000 systemic review on treatments for severe psoriasis. In this review, an additional 26 RCT reports examining phototherapy or photochemotherapy for psoriasis were identified. Among the studies were two RCTs comparing ultraviolet wavelength sources, five RCTs comparing different forms of phototherapy, four RCTs combining phototherapy with prior spa saline bathing, nine RCTs combining phototherapy with topical agents, two RCTs combining phototherapy with the systemic immunosuppressive agents methotrexate or alefacept, one RCT comparing phototherapy with an additional light source (the excimer laser), and one comparing a combination therapy with phototherapy and psychological intervention involving simultaneous audiotape sessions on mindfulness and stress reduction. Two trials also examined the effect of treatment setting on effectiveness of phototherapy, one on inpatient versus outpatient therapy and one on outpatient clinic versus home-based phototherapy. The conclusions of the MAS evidence-based review are outlined in Table ES1. In summary, phototherapy provides good control of clinical symptoms in the short term for patients with moderate-to-severe plaque-type psoriasis that have failed or are unresponsive to management with topical agents. However, many of the evidence gaps identified in the NIHR 2000 evidence review on psoriasis management persisted. In particular, the lack of evidence on the comparative effectiveness and/or cost-effectiveness between the major treatment options for moderate-to-severe psoriasis remained. The evidence on effectiveness and safety of longer term strategies for disease management has also not been addressed. Evidence for the safety, effectiveness, or cost-effectiveness of phototherapy delivered in various settings is emerging but is limited. In addition, because all available treatments for psoriasis - a disease with a high prevalence, chronicity, and cost - are palliative rather than curative, strategies for disease control and improvements in self-efficacy employed in other chronic disease management strategies should be investigated. (ABSTRACT TRUNCATED)

Neuroendocrine Disorders in Pediatric Craniopharyngioma Patients

PubMed Central

Daubenbüchel, Anna M. M.; Müller, Hermann L.

2015-01-01

Childhood-onset craniopharyngiomas are partly cystic embryonic malformations of the sellar/parasellar region. The therapy of choice in patients with favorable tumor localization is complete resection with a specific focus on maintaining optical and hypothalamic neuroendocrine functions. In patients with unfavorable tumor localization (i.e., hypothalamic involvement), a limited hypothalamus-sparing surgical strategy followed by local irradiation is recommended. Involvement and/or surgical lesions of posterior hypothalamic areas cause major neuroendocrine sequelae. The overall survival rates are high (92%) but neuroendocrine disorders such as obesity and metabolic syndrome due to involvement and/or treatment-related hypothalamic lesions have major negative impact on survival and quality of life. Recurrences and progressions are frequent post-surgical events. Because irradiation is efficient in preventing tumor progression, appropriate timing of post-surgical irradiation is currently under investigation in a randomized multinational trial (KRANIOPHARYNGEOM 2007). Childhood-onset craniopharyngioma should be recognized as a chronic disease requiring treatment and constant monitoring of the clinical and quality of life consequences, frequently impaired due to neuroendocrine disorders, by experienced multidisciplinary teams in order to provide optimal care of surviving patients. PMID:26239246

Task-specific Dystonias

PubMed Central

Torres-Russotto, Diego; Perlmutter, Joel S.

2009-01-01

Task-specific dystonias are primary focal dystonias characterized by excessive muscle contractions producing abnormal postures during selective motor activities that often involve highly skilled, repetitive movements. Historically these peculiar postures were considered psychogenic but have now been classified as forms of dystonia. Writer’s cramp is the most commonly identified task-specific dystonia and has features typical of this group of disorders. Symptoms may begin with lack of dexterity during performance of a specific motor task with increasingly abnormal posturing of the involved body part as motor activity continues. Initially, the dystonia may manifest only during the performance of the inciting task, but as the condition progresses it may also occur during other activities or even at rest. Neurological exam is usually unremarkable except for the dystonia-related abnormalities. Although the precise pathophysiology remains unclear, increasing evidence suggests reduced inhibition at different levels of the sensorimotor system. Symptomatic treatment options include oral medications, botulinum toxin injections, neurosurgical procedures, and adaptive strategies. Prognosis may vary depending upon body part involved and specific type of task affected. Further research may reveal new insights into the etiology, pathophysiology, natural history, and improved treatment of these conditions. PMID:18990127

Treatment of bacterial meningitis: an update.

PubMed

Shin, Seon Hee; Kim, Kwang Sik

2012-10-01

The introduction of protein conjugate vaccines for Haemophilus influenzae type b (Hib), Streptococcus pneumoniae (S. pneumoniae) and Neisseria meningitidis (N. menigitidis) has changed the epidemiology of bacterial meningitis. Bacterial meningitis continues to be an important cause of mortality and morbidity, and our incomplete knowledge of its pathogenesis and emergence of antimicrobial resistant bacteria contribute to such mortality and morbidity. An early empiric antibiotic treatment is critical for the management of patients with bacterial meningitis. This article gives an overview on optimal treatment strategies of bacterial meningitis, along with considerations of new insights on epidemiology, clinical and laboratory findings supportive of bacterial meningitis, chemoprophylaxis, selection of initial antimicrobial agents for suspected bacterial meningitis, antimicrobial resistance and utility of new antibiotics, status on anti-inflammatory agents and adjunctive therapy, and pathogenesis of bacterial meningitis. Prompt treatment of bacterial meningitis with an appropriate antibiotic is essential. Optimal antimicrobial treatment of bacterial meningitis requires bactericidal agents able to penetrate the blood-brain barrier (BBB), with efficacy in cerebrospinal fluid (CSF). Several new antibiotics have been introduced for the treatment of meningitis caused by resistant bacteria, but their use in human studies has been limited. More complete understanding of the microbial and host interactions that are involved in the pathogenesis of bacterial meningitis and associated neurologic sequelae is likely to help in developing new strategies for the prevention and therapy of bacterial meningitis.

Modification of the association between antipsychotic treatment response and childhood adversity by MMP9 gene variants in a first-episode schizophrenia cohort.

PubMed

McGregor, Nathaniel; Thompson, Nicole; O'Connell, Kevin Sean; Emsley, Robin; van der Merwe, Lize; Warnich, Louise

2018-04-01

Antipsychotics remain the most effective, and wide used option for ameliorating the symptoms of schizophrenia. However, inter-individual differences in treatment outcome are vast and suggest a role for genetic and environmental factors in affording favourable outcomes. A notable epigenetic relationship which has gained considerable traction in recent literature is the way in which the severity of childhood trauma can modify associations seen between genetic variation and antipsychotic treatment response. A potential mechanism of action which may facilitate this relationship is synaptic plasticity. This study investigated the role of variants in matrix metallopeptidase 9 (MMP9), a gene involved in synaptic plasticity, with treatment outcome considering the severity of childhood trauma as an interacting variable. The cohort comprised South African first episode schizophrenia patients treated with a single injectable antipsychotic, flupenthixol decanoate, monitored over 12 months. Relationships between novel and previously described variants, and haplotypes, with antipsychotic treatment response were found to be modified when considering childhood trauma as an interacting variable. This study provides the first evidence for the involvement of polymorphisms within MMP9 and the severity of childhood trauma in antipsychotic treatment response, and warrants further investigation into the role gene-environment interactions may play in the betterment of antipsychotic treatment strategies. Copyright © 2018 Elsevier B.V. All rights reserved.

Beyond Munchausen by proxy: a proposed conceptualization for cases of recurring, unsubstantiated sexual abuse allegations.

PubMed

Lindahl, Mary W

2009-01-01

In the emerging literature, cases involving recurring, unsubstantiated allegations of child sexual abuse have generally been categorized as Munchausen by proxy. Recent scholars have recommended restricting the label to the original conceptualization, involving purposeful deception motivated by psychological needs for medical attention. This leaves many cases unclassified that do not fit the Munchausen by proxy criteria, involve significant risks to the child, and ultimately fall outside of existing structures for Child Protective Services/legal intervention. This paper presents a reconceptualization of such cases, proposing to label them "recurring sexual abuse allegation" cases. Defining the set of cases more clearly can aid child protection workers in their management and encourage research on prevalence, consequences to children, treatment strategies, and needed legal reforms.

Chronic Osteomyelitis of the Distal Femur Treated with Resection and Delayed Endoprosthetic Reconstruction: A Report of Three Cases.

PubMed

Ryan, Sean; Eward, William; Brigman, Brian; Zura, Robert

2017-01-01

Chronic osteomyelitis involving the distal femur often results in amputation or arthrodesis. This article presents three cases of chronic osteomyelitis treated with a staged approach culminating in endoprosthetic reconstruction. Stage one involved resection of infected bone and placement of an intramedullary nail spanning the bony defect between proximal femur and tibia, with antibiotic cement packed around the nail. Patients were then placed on long-term IV +/- oral antibiotics to clear the infection. A "cooldown" period was then used between stages where patients were off antibiotics and inflammatory markers were monitored for signs of remaining infection. Stage two then involved reconstruction of the distal femur and knee with an endoprosthesis. In the appropriate patient, this treatment strategy offers another option in this challenging population.

Homicide-Followed-by-Suicide Incidents Involving Child Victims

PubMed Central

Logan, Joseph E.; Walsh, Sabrina; Patel, Nimeshkumar; Hall, Jeffrey E.

2015-01-01

Objectives To describe homicide-followed-by-suicide incidents involving child victims Methods Using 2003–2009 National Violent Death Reporting System data, we characterized 129 incidents based on victim and perpetrator demographic information, their relationships, the weapons/mechanisms involved, and the perpetrators’ health and stress-related circumstances. Results These incidents accounted for 188 child deaths; 69% were under 11 years old, and 58% were killed with a firearm. Approximately 76% of perpetrators were males, and 75% were parents/caregivers. Eighty-one percent of incidents with paternal perpetrators and 59% with maternal perpetrators were preceded by parental discord. Fifty-two percent of incidents with maternal perpetrators were associated with maternal psychiatric problems. Conclusions Strategies that resolve parental conflicts rationally and facilitate detection and treatment of parental mental conditions might help prevention efforts. PMID:23985234

Beyond CTLA-4 and PD-1, the Generation Z of Negative Checkpoint Regulators.

PubMed

Le Mercier, Isabelle; Lines, J Louise; Noelle, Randolph J

2015-01-01

In the last two years, clinical trials with blocking antibodies to the negative checkpoint regulators CTLA-4 and PD-1 have rekindled the hope for cancer immunotherapy. Multiple negative checkpoint regulators protect the host against autoimmune reactions but also restrict the ability of T cells to effectively attack tumors. Releasing these brakes has emerged as an exciting strategy for cancer treatment. Conversely, these pathways can be manipulated to achieve durable tolerance for treatment of autoimmune diseases and transplantation. In the future, treatment may involve combination therapy to target multiple cell types and stages of the adaptive immune responses. In this review, we describe the current knowledge on the recently discovered negative checkpoint regulators, future targets for immunotherapy.

Beyond CTLA-4 and PD-1, the Generation Z of Negative Checkpoint Regulators

PubMed Central

Le Mercier, Isabelle; Lines, J. Louise; Noelle, Randolph J.

2015-01-01

In the last two years, clinical trials with blocking antibodies to the negative checkpoint regulators CTLA-4 and PD-1 have rekindled the hope for cancer immunotherapy. Multiple negative checkpoint regulators protect the host against autoimmune reactions but also restrict the ability of T cells to effectively attack tumors. Releasing these brakes has emerged as an exciting strategy for cancer treatment. Conversely, these pathways can be manipulated to achieve durable tolerance for treatment of autoimmune diseases and transplantation. In the future, treatment may involve combination therapy to target multiple cell types and stages of the adaptive immune responses. In this review, we describe the current knowledge on the recently discovered negative checkpoint regulators, future targets for immunotherapy. PMID:26347741

Emerging immunotherapy and strategies directly targeting B cells for the treatment of diffuse large B-cell lymphoma.

PubMed

Witkowska, Magdalena; Smolewski, Piotr

2015-01-01

During the last decade, significant prolonged survival in diffusive large B-cell lymphoma (DLBCL) has been observed. The efficacy of initial treatment improved mostly due to addition of a chimeric anti-CD20 monoclonal antibody (rituximab) to standard chemotherapeutic regimens. Moreover, accurate understanding of DLBCL pathogenesis and remarkable progress in gene expression profiling have led to the development of a variety of tumor-specific regimens. Novel agents target directly the pathways involved in signal transduction, lead to apoptosis and cancer cells differentiation. In this article, we mainly focus on new treatment options, such as monoclonal antibodies, tyrosine kinase inhibitors and immunomodulatory drugs, currently investigated in aggressive B-cell lymphoma with particular attention to DLBCL type.

Current Treatment and Recent Clinical Research in Alzheimer's Disease

PubMed Central

Neugroschl, Judith; Sano, Mary

2010-01-01

The transition from either epidemiological observation or the bench to rigorously tested clinical trials in patients with Alzheimer's disease is crucial in understanding which treatments are beneficial to patients. The amyloid hypothesis has undergone scrutiny recently, as many trials aimed at reducing amyloid and plaque have been completed or are in the testing phase. Examples include modulation of the secretases involved in beta amyloid formation, anti-aggregation agents, and immunotherapeutic trials. Other therapies targeting hyperphosphorylated tau and novel targets such as enhancement of mitochondrial function, serotonin receptors, receptor for advanced glycation end products, and nerve growth factor, as well as other strategies, are discussed. A brief review of the current Food and Drug Administration–approved treatments is included. PMID:20101716

Implementing family-focused HIV care and treatment: the first 2 years' experience of the mother-to-child transmission-plus program in Abidjan, Côte d'Ivoire

PubMed Central

Tonwe-Gold, Besigin; Ekouevi, Didier Koumavi; Amani-Bosse, Clarisse; Toure, Siaka; Koné, Mamadou; Becquet, Renaud; Leroy, Valériane; Toro, Patricia; Dabis, François; El Sadr, Wafaa M.; Abrams, Elaine J.

2009-01-01

Summary Objectives To describe a family-focused approach to HIV care and treatment and report on the first two years’ experience of implementing the MTCT-Plus program in Abidjan, Côte d’Ivoire. Program implementation New effective models of care are being sought to provide successful strategies to deliver safe, efficient and appropriate HIV care and treatment in resource limited settings. The MTCT-Plus Initiative aims to engage pregnant and postpartum women identified as HIV-infected to initiate comprehensive HIV care and treatment for the woman and her family. Main outcomes Between August 2003 and August 2005, 605 HIV-infected pregnant or post-partum women and 582 HIV-exposed infants were enrolled. Amongst 568 male partners reported alive by enrolled women, 300 (52%) were aware of their wife’s HIV status and 169 (30%) have been tested for HIV. Amongst these partners, 88 (53%) were found to be HIV-infected and 69 (78%) were enrolled into the program. Overall only 10% of the women were enrolled together with their infected partner. On the other hand, a success of the program was also to involve a significant number of seronegative men (half of those who came for VCT) in the care of their families. Amongst 1,624 children <15 years reported alive by their mothers (excluding the last newborn infants of the most recent pregnancy systematically screened for HIV), only 146 (10.8%) were brought in for HIV testing, of whom 18 (12.3%) were found to be HIV-infected. Lessons learned and challenges The family-focused model of HIV care pays attention to the needs of families and household members. The program was successful in enrolling HIV women, their partners and infants in continuous follow-up. However engaging partners and family members of newly enrolled women into care involves numerous challenges outlined in the cascade of necessary events that must take place to achieve this goal. This involves the difficult issue of disclosure of HIV status by women to their partners and family members. Further efforts are required to understand barriers for families accessing HIV services as strategies to improve partner involvement and provide access to care for other children in the households are needed in this West African urban setting. PMID:19236666

Improving Written Language Performance of Adolescents with Asperger Syndrome

PubMed Central

Delano, Monica E

2007-01-01

The effects of a multicomponent intervention involving self-regulated strategy development delivered via video self-modeling on the written language performance of 3 students with Asperger syndrome were examined. During intervention sessions, each student watched a video of himself performing strategies for increasing the number of words written and the number of functional essay elements. He then wrote a persuasive essay. The number of words written and number of functional essay elements included in each essay were measured. Each student demonstrated gains in the number of words written and number of functional essay elements. Maintenance of treatment effects at follow-up varied across targets and participants. Implications for future research are suggested. PMID:17624076

New medications for substance use disorders: challenges and opportunities.

PubMed

Volkow, Nora D; Skolnick, Phil

2012-01-01

An increased understanding of the biological mechanisms underlying the process of addiction has led to unique molecular targets and strategies for pharmacotherapies against addiction. However, the successful translation of these discoveries will require: 1) a more active engagement of the pharmaceutical sector, 2) partnership with regulatory agencies to arrive at meaningful outcomes for medication approval and 3) a greater involvement of the healthcare system in the screening and treatment of substance use disorders.

An ICT and mobile health integrated approach to optimize patients' education on hypertension and its management by physicians: The Patients Optimal Strategy of Treatment(POST) pilot study.

PubMed

Albini, Fabio; Xiaoqiu Liu; Torlasco, Camilla; Soranna, Davide; Faini, Andrea; Ciminaghi, Renata; Celsi, Ada; Benedetti, Matteo; Zambon, Antonella; di Rienzo, Marco; Parati, Gianfranco

2016-08-01

Uncontrolled hypertension is largely attributed to unsatisfactory doctor's engagement in its optimal management and to poor patients' compliance to therapeutic interventions. ICT and mobile Health solutions might improve these conditions, being widely available and providing highly effective communication strategies. To evaluate whether ICT and mobile Health tools are able to improve hypertension control by improving doctors' engagement and by increasing patients' education and involvement, and their compliance to lifestyle modification and prescribed drug therapy. In a pilot study, we have included 690 treated hypertensive patients with uncontrolled office blood pressure (BP), consecutively recruited by 9 general practitioners over 3 months. Patients were alternatively assigned to routine management based on repeated office visits or to an integrated ICT-based Patients Optimal Strategy for Treatment (POST) system including Home BP monitoring teletransmission, a dedicated web-based platform for patients' management by physicians (Misuriamo platform), and a smartphone mobile application (Eurohypertension APP, E-APP), over a follow-up of 6 months. BP values, demographic and clinical data were collected at baseline and at all follow-up visits (at least two). BP control and cardiovascular risk level have been evaluated at the beginning and at the end of the study. 89 patients did not complete the follow-up, thus data analysis was carried out in 601 of them (303 patients in the POST group and 298 in the control group). Office BP control (<;149/90 mmHg) was 40.0% in control group, and 72.3% in POST group at 6 month follow-up. At the same time Home BP control (<;135/85 mmHg average of 6 days) in POST group was 87.5%. this pilot study suggests that ICT based tools might be effective in improving hypertension management, implementing positive patients' involvement with better adherence to treatment prescriptions and providing the physicians with dynamic control of patients' home BP measurements, resulting in lesser clinical inertia.

Conducting indirect-treatment-comparison and network-meta-analysis studies: report of the ISPOR Task Force on Indirect Treatment Comparisons Good Research Practices: part 2.

PubMed

Hoaglin, David C; Hawkins, Neil; Jansen, Jeroen P; Scott, David A; Itzler, Robbin; Cappelleri, Joseph C; Boersma, Cornelis; Thompson, David; Larholt, Kay M; Diaz, Mireya; Barrett, Annabel

2011-06-01

Evidence-based health care decision making requires comparison of all relevant competing interventions. In the absence of randomized controlled trials involving a direct comparison of all treatments of interest, indirect treatment comparisons and network meta-analysis provide useful evidence for judiciously selecting the best treatment(s). Mixed treatment comparisons, a special case of network meta-analysis, combine direct evidence and indirect evidence for particular pairwise comparisons, thereby synthesizing a greater share of the available evidence than traditional meta-analysis. This report from the International Society for Pharmacoeconomics and Outcomes Research Indirect Treatment Comparisons Good Research Practices Task Force provides guidance on technical aspects of conducting network meta-analyses (our use of this term includes most methods that involve meta-analysis in the context of a network of evidence). We start with a discussion of strategies for developing networks of evidence. Next we briefly review assumptions of network meta-analysis. Then we focus on the statistical analysis of the data: objectives, models (fixed-effects and random-effects), frequentist versus Bayesian approaches, and model validation. A checklist highlights key components of network meta-analysis, and substantial examples illustrate indirect treatment comparisons (both frequentist and Bayesian approaches) and network meta-analysis. A further section discusses eight key areas for future research. Copyright © 2011 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

The neurocircuitry of illicit psychostimulant addiction: acute and chronic effects in humans

PubMed Central

Taylor, Sara B; Lewis, Candace R; Olive, M Foster

2013-01-01

Illicit psychostimulant addiction remains a significant problem worldwide, despite decades of research into the neural underpinnings and various treatment approaches. The purpose of this review is to provide a succinct overview of the neurocircuitry involved in drug addiction, as well as the acute and chronic effects of cocaine and amphetamines within this circuitry in humans. Investigational pharmacological treatments for illicit psychostimulant addiction are also reviewed. Our current knowledge base clearly demonstrates that illicit psychostimulants produce lasting adaptive neural and behavioral changes that contribute to the progression and maintenance of addiction. However, attempts at generating pharmacological treatments for psychostimulant addiction have historically focused on intervening at the level of the acute effects of these drugs. The lack of approved pharmacological treatments for psychostimulant addiction highlights the need for new treatment strategies, especially those that prevent or ameliorate the adaptive neural, cognitive, and behavioral changes caused by chronic use of this class of illicit drugs. PMID:24648786

[Indications for Retinal Laser Therapy Revisited].

PubMed

Enders, P; Schaub, F; Fauser, S

2017-02-10

Background Laser therapy is an important treatment option in retinal diseases, especially in cases of vascular involvement. Most approaches are based on coagulation of retinal structures. As there is increasing use of agents targetting vascular endothelial growth factor in the treatment of macular diseases, indications for the use of laser treatment need to be reviewed carefully, especially with respect to their significance in first line therapy. This article explains recent strategies and treatment protocols. Materials and Methods Review of current literature in PubMed as well as synopsis of relevant guidelines. Results and Conclusion Retinal laser therapy is still widely used within retinal opthalmology and covers a large spectrum of indications. Despite the success of medical approaches, retinal laser therapy remains an indispensable treatment option for proliferative diabetic retinopathy, central or peripheral vein occlusion and less frequent pathologies, such as retinopathy of prematurity or Coats's disease. Georg Thieme Verlag KG Stuttgart · New York.

Building Evidence-Based Tobacco Treatment in the Eastern Mediterranean Region: Lessons Learned by the Syrian Center for Tobacco Studies

PubMed Central

Asfar, Taghrid; Ward, Kenneth D.; Al-Ali, Radwan; Maziak, Wasim

2016-01-01

The tobacco epidemic in Syria is characterized by high rates of cigarettes smoking in men and dramatic reemergence of waterpipe smoking, especially among youths and women. The Syrian Center for Tobacco Studies (SCTS), an NIH-funded pioneer research and capacity building institution, has developed a research infrastructure and conducted three randomized clinical trials to develop and rigorously test culturally-appropriate tobacco treatment programs integrated into primary healthcare (PHC) centers. This review aimed to discuss challenges and lessons learned from the Syrian experience. Addressing these challenges may inform future cessation research activities in Syria and other developing countries. To develop a research infrastructure, the SCTS has established Syria’s first IRB and trained physicians/medical students in both tobacco treatment and research methods. Main challenges to conduct the cessation trials were difficulties of coordination between the local and international collaborators; high Smoking Rates among PHC providers; lack of pharmacological agents used in tobacco treatment; and difficulties of conducting research in a politically volatile region. Strategies to overcome these challenges were ensuring an active and regular involvement of all investigator; and advocating for a national smoking-cessation plan that involves training health care providers in smoking cessation treatment and make pharmacological agents used in smoking cessation available. PMID:27563356

Relationships Among Adaptive and Maladaptive Emotion Regulation Strategies and Psychopathology During the Treatment of Comorbid Anxiety and Alcohol Use Disorders

PubMed Central

Conklin, Laren R.; Cassiello-Robbins, Clair; Brake, C. Alex; Sauer-Zavala, Shannon; Farchione, Todd J.; Ciraulo, Domenic A.; Barlow, David H.

2015-01-01

Both maladaptive and adaptive emotion regulation strategies have been linked with psychopathology. However, previous studies have largely examined them separately, and little research has examined the interplay of these strategies cross-sectionally or longitudinally in patients undergoing psychological treatment. This study examined the use and interplay of adaptive and maladaptive emotion regulation strategies in 81 patients receiving cognitive-behavioral interventions for comorbid alcohol use and anxiety disorders. Patients completed measures of emotion regulation strategy use and symptoms of psychopathology pre- and post-treatment. Cross-sectionally, higher use of maladaptive strategies (e.g., denial) was significantly related to higher psychopathology pre- and post-treatment, whereas higher use of adaptive strategies (e.g., acceptance) only significantly related to lower psychopathology post-treatment. Prospectively, changes in maladaptive strategies, but not changes in adaptive strategies, were significantly associated with post-treatment psychopathology. However, for patients with higher pre-treatment maladaptive strategy use, gains in adaptive strategies were significantly associated with lower post-treatment psychopathology. These findings suggest that psychological treatments may maximize efficacy by considering patient skill use at treatment outset. By better understanding a patient's initial emotion regulation skills, clinicians may be better able to optimize treatment outcomes by emphasizing maladaptive strategy use reduction predominately, or in conjunction with increasing adaptive skill use. PMID:26310363

Root Resorption: Simplifying Diagnosis and Improving Outcomes.

PubMed

Darcey, James; Qualtrough, Alison

2016-05-01

Root resorption is a condition resulting in the progressive loss of dental hard tissue. It may occur both within the root and upon the external aspect of the root. Diagnosis can be difficult and management challenging. Understanding the pathology is critical to understanding why and when this disease occurs and what the best management techniques involve. With such knowledge practitioners can confidently diagnose resorption, discuss prognoses and management strategies with the patient and either refer or begin treatment. Early intervention is paramount in improving outcomes. As such, if practitioners choose to refer patients they must be aware of what can be done immediately to mitigate risks until consultation and specialist treatment begins.

Post-glossectomy in lingual carcinomas: a scope for sign language in rehabilitation

PubMed Central

Cumberbatch, Keren; Jones, Thaon

2017-01-01

The treatment option for cancers of the tongue is glossectomy, which may be partial, sub-total, or total, depending on the size of the tumour. Glossectomies result in speech deficits for these patients, and rehabilitative therapy involving communication modalities is highly recommended. Sign language is a possible therapeutic solution for post-glossectomy oral cancer patients. Patients with tongue cancers who have undergone total glossectomy as a surgical treatment can utilise sign language to replace their loss of speech production and maintain their engagement in life. This manuscript emphasises the importance of sign language in rehabilitation strategies in post-glossectomy patients. PMID:28947881

Post-glossectomy in lingual carcinomas: a scope for sign language in rehabilitation.

PubMed

Rajendra Santosh, Arvind Babu; Cumberbatch, Keren; Jones, Thaon

2017-01-01

The treatment option for cancers of the tongue is glossectomy, which may be partial, sub-total, or total, depending on the size of the tumour. Glossectomies result in speech deficits for these patients, and rehabilitative therapy involving communication modalities is highly recommended. Sign language is a possible therapeutic solution for post-glossectomy oral cancer patients. Patients with tongue cancers who have undergone total glossectomy as a surgical treatment can utilise sign language to replace their loss of speech production and maintain their engagement in life. This manuscript emphasises the importance of sign language in rehabilitation strategies in post-glossectomy patients.

Recovery from Bell Palsy after Transplantation of Peripheral Blood Mononuclear Cells and Platelet-Rich Plasma.

PubMed

Seffer, Istvan; Nemeth, Zoltan

2017-06-01

Peripheral blood mononuclear cells (PBMCs) are multipotent, and plasma contains growth factors involving tissue regeneration. We hypothesized that transplantation of PBMC-plasma will promote the recovery of paralyzed facial muscles in Bell palsy. This case report describes the effects of PBMC-plasma transplantations in a 27-year-old female patient with right side Bell palsy. On the affected side of the face, the treatment resulted in both morphological and functional recovery including voluntary facial movements. These findings suggest that PBMC-plasma has the capacity of facial muscle regeneration and provides a promising treatment strategy for patients suffering from Bell palsy or other neuromuscular disorders.

The Experience of Couples in the Process of Treatment of Pathological Gambling: Couple vs. Individual Therapy.

PubMed

Tremblay, Joël; Dufour, Magali; Bertrand, Karine; Blanchette-Martin, Nadine; Ferland, Francine; Savard, Annie-Claude; Saint-Jacques, Marianne; Côté, Mélissa

2017-01-01

Context: Couple treatment for pathological gambling is an innovative strategy. There are some results supporting its potential effectiveness, but little is known about the subjective experiences of the participants. Objective: The aim of this article is to document the experiences of gamblers and their partners participating in one of two treatments, namely individual or couple. Method: In a study aiming to evaluate the efficacy of the Integrative Couple Treatment for Pathological Gambling (ICT-PG), couples who were entering specialized treatment for the addiction of one member who was a pathological gambler were randomly assigned to individual or ICT-PG. Nine months after their admission to treatment, gamblers and partners ( n = 21 couples; n = 13 ICT-PG; n = 8 individual treatment) were interviewed in semi-structured interviews. A sequenced thematization method was used to extract the major themes. Results: This study highlighted five major themes in the therapeutic process noted by the gamblers and their partners mainly after the couple treatment but also partly through the individual therapy. These were: (1) the gamblers' anxiety about having to reveal their gambling problems in couple therapy; (2) the wish to develop a mutually beneficial understanding of gambling and its effects on the partners in the two types of treatments; (3) the transformation of negative attributions through a more effective intra-couple communication fostered by the couple therapy; (4) the partners' contribution to changes in gambling behavior and prevention of relapses, which were both better supported in couple therapy; and (5) the interpersonal nature of gambling and its connections with the couples' relationship. However, gamblers who were in individual treatment were more likely to mention that their partners' involvement was not necessary. Participants likewise made a few recommendations about the conditions underlying the choice of one treatment method or the other. Discussion: Participants reported satisfaction with both treatment models, but their experience was more positive in couple treatment. Complementary benefits emerged from each form of treatment, which points to future treatments involving both types. Future research should explore both the couple processes associated with attempts to stop pathological gambling and the various ways of involving partners in the gamblers' treatment.

The Experience of Couples in the Process of Treatment of Pathological Gambling: Couple vs. Individual Therapy

PubMed Central

Tremblay, Joël; Dufour, Magali; Bertrand, Karine; Blanchette-Martin, Nadine; Ferland, Francine; Savard, Annie-Claude; Saint-Jacques, Marianne; Côté, Mélissa

2018-01-01

Context: Couple treatment for pathological gambling is an innovative strategy. There are some results supporting its potential effectiveness, but little is known about the subjective experiences of the participants. Objective: The aim of this article is to document the experiences of gamblers and their partners participating in one of two treatments, namely individual or couple. Method: In a study aiming to evaluate the efficacy of the Integrative Couple Treatment for Pathological Gambling (ICT-PG), couples who were entering specialized treatment for the addiction of one member who was a pathological gambler were randomly assigned to individual or ICT-PG. Nine months after their admission to treatment, gamblers and partners (n = 21 couples; n = 13 ICT-PG; n = 8 individual treatment) were interviewed in semi-structured interviews. A sequenced thematization method was used to extract the major themes. Results: This study highlighted five major themes in the therapeutic process noted by the gamblers and their partners mainly after the couple treatment but also partly through the individual therapy. These were: (1) the gamblers' anxiety about having to reveal their gambling problems in couple therapy; (2) the wish to develop a mutually beneficial understanding of gambling and its effects on the partners in the two types of treatments; (3) the transformation of negative attributions through a more effective intra-couple communication fostered by the couple therapy; (4) the partners' contribution to changes in gambling behavior and prevention of relapses, which were both better supported in couple therapy; and (5) the interpersonal nature of gambling and its connections with the couples' relationship. However, gamblers who were in individual treatment were more likely to mention that their partners' involvement was not necessary. Participants likewise made a few recommendations about the conditions underlying the choice of one treatment method or the other. Discussion: Participants reported satisfaction with both treatment models, but their experience was more positive in couple treatment. Complementary benefits emerged from each form of treatment, which points to future treatments involving both types. Future research should explore both the couple processes associated with attempts to stop pathological gambling and the various ways of involving partners in the gamblers' treatment. PMID:29416520

Intervention for the control of Soil -transmitted helminthiasis in the community

PubMed Central

Albonico, Marco; Montresor, Antonio; Crompton, DWT; Savioli, Lorenzo

2017-01-01

The global strategy for the control of soil-transmitted helminthiasis, based on regular anthelminthic treatment, health education, and improved sanitation standards, is reviewed. The reasons for the development of a control strategy based on population intervention rather than on individual treatment are explained. The evidence and experience from control programmes that created the basis for i) the definition of the intervention package, ii) the identification of the groups at risk, iii) the standardization of the community diagnosis, and iv) the selection of the appropriate intervention for each category in the community are discussed. How to best deliver the appropriate intervention, the impact of the control measures on morbidity and on indicators such as school attendance, cognitive development and productivity are presented. The factors influencing the cost-benefits of helminth control are also considered. The recent progress on the control of soil-transmitted helminth infections is illustrated. Research needs are analysed in relation to the most recent perceptions from private-public partnerships involved in helminth control. The way forward for the control of soil-transmitted helminth infections is described as a multi-disease approach that goes beyond deworming and fosters a pro-poor strategy that supports the aims of the Millennium Development Goals. PMID:16735168

Strategies for More Rapid Translation of Cellular Therapies for Children: A US Perspective

PubMed Central

Silberstein, Leslie E.; Lindblad, Robert W.; Welniak, Lisbeth A.; Mondoro, Traci Heath; Wagner, John E.

2013-01-01

Clinical trials for pediatric diseases face many challenges, including trial design, accrual, ethical considerations for children as research subjects, and the cost of long-term follow-up studies. In September 2011, the Production Assistance for Cellular Therapies Program, funded by the National Heart, Lung, and Blood Institute of the National Institutes of Health, sponsored a workshop, “Cell Therapy for Pediatric Diseases: A Growing Frontier,” with the overarching goal of optimizing the path of discovery in research involving novel cellular therapeutic interventions for debilitating pediatric conditions with few or no available treatment options. Academic and industry investigators in the fields of cellular therapy and regenerative medicine described the obstacles encountered in conducting a clinical trial from concept to conclusion. Patient and parent advocates, bioethicists, biostatisticians, regulatory representatives from the US Food and Drug Administration, and translational scientists actively participated in this workshop, seeking to identify the unmet needs specific to cellular therapies and treatment of pediatric diseases and propose strategies to facilitate the development of novel therapies. In this article we summarize the obstacles and potential corrective strategies identified by workshop participants to maximize the speed of cell therapy translational research for childhood diseases. PMID:23837178

Management strategies in pancreatic cancer.

PubMed

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

2011-04-01

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

Marine Invertebrate Metabolites with Anticancer Activities: Solutions to the “Supply Problem”

PubMed Central

Gomes, Nelson G. M.; Dasari, Ramesh; Chandra, Sunena; Kiss, Robert; Kornienko, Alexander

2016-01-01

Marine invertebrates provide a rich source of metabolites with anticancer activities and several marine-derived agents have been approved for the treatment of cancer. However, the limited supply of promising anticancer metabolites from their natural sources is a major hurdle to their preclinical and clinical development. Thus, the lack of a sustainable large-scale supply has been an important challenge facing chemists and biologists involved in marine-based drug discovery. In the current review we describe the main strategies aimed to overcome the supply problem. These include: marine invertebrate aquaculture, invertebrate and symbiont cell culture, culture-independent strategies, total chemical synthesis, semi-synthesis, and a number of hybrid strategies. We provide examples illustrating the application of these strategies for the supply of marine invertebrate-derived anticancer agents. Finally, we encourage the scientific community to develop scalable methods to obtain selected metabolites, which in the authors’ opinion should be pursued due to their most promising anticancer activities. PMID:27213412

Antimicrobial formulary management: meeting the challenge in the community hospital.

PubMed

Rush, D R

1991-01-01

We established a casework approach to develop an antibiotic formulary for a large community hospital. The program consists of a combination of comprehensive clinical and administrative strategies designed to reduce antimicrobial expenditures and improve the quality of antibiotic prescribing. Strategies included a background document summarizing each pharmacologic group of antimicrobial drugs and formulary preferences, presentations to medical and surgical departments, development of drug use evaluation strategies that complement the development of the formulary, and a monitoring program for nonformulary antibiotic use. The development of a customized microbiologic/antibiotic susceptibility report card specific to the institution's inpatient and outpatient microflora was an integral part of the program. This tool also allowed for the continuous compilation of comparison data and development of prescribing tips. Predetermined criteria were established providing physicians with microorganism susceptibility reports and preferred treatment alternatives linked to pharmacoeconomic concerns. These strategies can be implemented with or without direct clinical pharmacotherapy specialist involvement at the individual patient care level.

The costs of HIV prevention strategies in developing countries.

PubMed Central

Söderlund, N.; Lavis, J.; Broomberg, J.; Mills, A.

1993-01-01

Since many evaluations of HIV (human immunodeficiency virus) prevention programmes do not include data on costs, a preliminary analysis of the costs and outputs of a sample of HIV prevention projects was attempted. Case studies, representing six broad HIV prevention strategies in developing countries with differing levels of per capita gross domestic product, were sought on the basis of availability of data and potential generalizability. The six prevention strategies studied were mass media campaigns, peer education programmes, sexually transmitted disease treatment, condom social marketing, safe blood provision, and needle exchange/bleach provision programmes. Financial cost data were abstracted from published studies or were obtained directly from project coordinators. Although estimates of cost-effectiveness were not made, calculations of the relative cost per common process measure of output were compared. Condom distribution costs ranged from US$ 0.02 to 0.70 per condom distributed, and costs of strategies involving personal educational input ranged from US$ 0.15 to 12.59 per contact. PMID:8261563

LEARNING TO CHOOSE AMONG SOCIAL FORAGING STRATEGIES IN ADULT HOUSE SPARROWS (Passer domesticus)

PubMed Central

Belmaker, Amos; Motro, Uzi; Feldman, Marcus W.; Lotem, Arnon

2012-01-01

Social foragers may be regarded as being engaged in a producer-scrounger game in which they can search for food independently or join others who have discovered food. Research on the producer-scrounger game has focused mainly on the different factors influencing its ESS solution, but very little is known about the actual mechanisms that shape players’ decisions. Recent work has shown that early experience can affect producer-scrounger foraging tendencies in young house sparrows, and that in nutmeg mannikins learning is involved in reaching the ESS. Here we show that direct manipulation of the success rate experienced by adult sparrows when following others can change their strategy choice on the following day. We presented to live sparrows an experimental regime, where stuffed adult house sparrows in a feeding position were positioned on a foraging grid that included two reward regimes: a positive one, in which the stuffed models were placed near food, and a negative one, in which the models were placed away from food. There was a significant increase in joining behavior after the positive treatment (exhibited by 84% of the birds), but no change after the negative treatment. Further analysis demonstrated that sparrows more frequently used the strategy with which they were more successful (usually joining), and that differences in strategy use were correlated with differences in success. These results suggest that adult birds can monitor their success and learn to choose among social foraging strategies in the producer-scrounger game. PMID:23226911

Treatment of Adolescent Substance Use Disorders and Co-Occurring Internalizing Disorders: A Critical Review and Proposed Model.

PubMed

Hulvershorn, Leslie A; Quinn, Patrick D; Scott, Eric L

2015-01-01

The past several decades have seen dramatic growth in empirically supported treatments for adolescent substance use disorders (SUDs), yet even the most well-established approaches struggle to produce large or long-lasting improvements. These difficulties may stem, in part, from the high rates of comorbidity between SUDs and other psychiatric disorders. We critically reviewed the treatment outcome literature for adolescents with co-occurring SUDs and internalizing disorders. Our review identified components of existing treatments that might be included in an integrated, evidence-based approach to the treatment of SUDs and internalizing disorders. An effective program may involve careful assessment, inclusion of parents or guardians, and tailoring of interventions via a modular strategy. The existing literature guides the development of a conceptual evidence-based, modular treatment model targeting adolescents with co-occurring internalizing and SUDs. With empirical study, such a model may better address treatment outcomes for both disorder types in adolescents.

Treatment of Adolescent Substance Use Disorders and Co-Occurring Internalizing Disorders: A Critical Review and Proposed Model

PubMed Central

Hulvershorn, Leslie A.; Quinn, Patrick D.; Scott, Eric L.

2016-01-01

Background The past several decades have seen dramatic growth in empirically supported treatments for adolescent substance use disorders (SUDs), yet even the most well-established approaches struggle to produce large or long-lasting improvements. These difficulties may stem, in part, from the high rates of comorbidity between SUDs and other psychiatric disorders. Method We critically reviewed the treatment outcome literature for adolescents with co-occurring SUDs and internalizing disorders. Results Our review identified components of existing treatments that might be included in an integrated, evidence-based approach to the treatment of SUDs and internalizing disorders. An effective program may involve careful assessment, inclusion of parents or guardians, and tailoring of interventions via a modular strategy. Conclusions The existing literature guides the development of a conceptual evidence-based, modular treatment model targeting adolescents with co-occurring internalizing and SUDs. With empirical study, such a model may better address treatment outcomes for both disorder types in adolescents. PMID:25973718

The development of an RDoC-based treatment program for adolescent depression: “Training for Awareness, Resilience, and Action” (TARA)

PubMed Central

Henje Blom, Eva; Duncan, Larissa G.; Ho, Tiffany C.; Connolly, Colm G.; LeWinn, Kaja Z.; Chesney, Margaret; Hecht, Frederick M.; Yang, Tony T.

2014-01-01

Major depressive disorder (MDD) is one of the current leading causes of disability worldwide. Adolescence is a vulnerable period for the onset of depression, with MDD affecting 8–20% of all youth. Traditional treatment methods have not been sufficiently effective to slow the increasing prevalence of adolescent depression. We therefore propose a new model for the treatment of adolescent depression – Training for Awareness, Resilience, and Action (TARA) – that is based on current understanding of developmental and depression neurobiology. The TARA model is aligned with the Research Domain Criteria (RDoC) of the National Institute of Mental Health. In this article, we first address the relevance of RDoC to adolescent depression. Second, we identify the major RDoC domains of function involved in adolescent depression and organize them in a way that gives priority to domains thought to be driving the psychopathology. Third, we select therapeutic training strategies for TARA based on current scientific evidence of efficacy for the prioritized domains of function in a manner that maximizes time, resources, and feasibility. The TARA model takes into consideration the developmental limitation in top-down cognitive control in adolescence and promotes bottom-up strategies such as vagal afference to decrease limbic hyperactivation and its secondary effects. The program has been informed by mindfulness-based therapy and yoga, as well as modern psychotherapeutic techniques. The treatment program is semi-manualized, progressive, and applied in a module-based approach designed for a group setting that is to be conducted one session per week for 12 weeks. We hope that this work may form the basis for a novel and more effective treatment strategy for adolescent depression, as well as broaden the discussion on how to address this challenge. PMID:25191250

Using the "customer service framework" to successfully implement patient- and family-centered care.

PubMed

Rangachari, Pavani; Bhat, Anita; Seol, Yoon-Ho

2011-01-01

Despite the growing momentum toward patient- and family-centered care at the federal policy level, the organizational literature remains divided on its effectiveness, especially in regard to its key dimension of involving patients and families in treatment decisions and safety practices. Although some have argued for the universal adoption of patient involvement, others have questioned both the effectiveness and feasibility of patient involvement. In this article, we apply a well-established theoretical perspective, that is, the Service Quality Model (SQM) (also known as the "customer service framework") to the health care context, to reconcile the debate related to patient involvement. The application helps support the case for universal adoption of patient involvement and also question the arguments against it. A key contribution of the SQM lies in highlighting a set of fundamental service quality determinants emanating from basic consumer service needs. It also provides a simple framework for understanding how gaps between consumer expectations and management perceptions of those expectations can affect the gap between "expected" and "perceived" service quality from a consumer's perspective. Simultaneously, the SQM also outlines "management requirements" for the successful implementation of a customer service strategy. Applying the SQM to the health care context therefore, in addition to reconciling the debate on patient involvement, helps identify specific steps health care managers could take to successfully implement patient- and family-centered care. Correspondingly, the application also provides insights into strategies for the successful implementation of policy recommendations related to patient- and family-centered care in health care organizations.

Activation of microbubbles by low-intensity pulsed ultrasound enhances the cytotoxicity of curcumin involving apoptosis induction and cell motility inhibition in human breast cancer MDA-MB-231 cells.

PubMed

Li, Yixiang; Wang, Pan; Chen, Xiyang; Hu, Jianmin; Liu, Yichen; Wang, Xiaobing; Liu, Quanhong

2016-11-01

Ultrasound and microbubbles-mediated drug delivery has become a promising strategy to promote drug delivery and its therapeutic efficacy. The aim of this research was to assess the effects of microbubbles (MBs)-combined low-intensity pulsed ultrasound (LPUS) on the delivery and cytotoxicity of curcumin (Cur) to human breast cancer MDA-MB-231 cells. Under the experimental condition, MBs raised the level of acoustic cavitation and enhanced plasma membrane permeability; and cellular uptake of Cur was notably improved by LPUS-MBs treatment, aggravating Cur-induced MDA-MB-231 cells death. The combined treatment markedly caused more obvious changes of cell morphology, F-actin cytoskeleton damage and cell migration inhibition. Our results demonstrated that combination of MBs and LPUS may be an efficient strategy for improving anti-tumor effect of Cur, suggesting a potential effective method for antineoplastic therapy. Copyright © 2016 Elsevier B.V. All rights reserved.

A Rare Presentation of Isolated CNS Posttransplantation Lymphoproliferative Disorder

PubMed Central

Smith, Casey; Streicher, Andrew; Magnuson, Allison; Newman, Susan; Bertoli, Robert

2017-01-01

Posttransplantation lymphoproliferative disorder (PTLD) is a recognized and extremely morbid complication of solid organ transplantation, but central nervous system involvement, particularly in isolation, is rare. There are no standardized treatment strategies for PTLD, though commonly used strategies include reduction of immunosuppression, chemotherapy, rituximab, radiation, and surgery. We present a case of an unusual morphologic variant of primary central nervous system PTLD with successful response to rituximab and cranial radiation. A 69-year-old Asian male, who underwent postrenal transplant nine years earlier, presented with a one-month history of new onset seizure activity. His evaluation revealed multiple brain lesions on magnetic resonance imaging (MRI), as well as serologic and cerebrospinal fluid studies which were positive for Epstein-Barr Virus (EBV) infection. Ultimately, he underwent craniotomy with tissue biopsy with the final pathology report showing posttransplant lymphoproliferative disorder, polymorphic type. The patient was managed with reduction in immunosuppression, rituximab therapy, and cranial radiation treatments. He had demonstrated marked improvement in his neurologic function and was ultimately discharged to inpatient rehabilitation facility. PMID:28116196

A Rare Presentation of Isolated CNS Posttransplantation Lymphoproliferative Disorder.

PubMed

Morris, Jaime; Smith, Casey; Streicher, Andrew; Magnuson, Allison; Newman, Susan; Bertoli, Robert

2017-01-01

Posttransplantation lymphoproliferative disorder (PTLD) is a recognized and extremely morbid complication of solid organ transplantation, but central nervous system involvement, particularly in isolation, is rare. There are no standardized treatment strategies for PTLD, though commonly used strategies include reduction of immunosuppression, chemotherapy, rituximab, radiation, and surgery. We present a case of an unusual morphologic variant of primary central nervous system PTLD with successful response to rituximab and cranial radiation. A 69-year-old Asian male, who underwent postrenal transplant nine years earlier, presented with a one-month history of new onset seizure activity. His evaluation revealed multiple brain lesions on magnetic resonance imaging (MRI), as well as serologic and cerebrospinal fluid studies which were positive for Epstein-Barr Virus (EBV) infection. Ultimately, he underwent craniotomy with tissue biopsy with the final pathology report showing posttransplant lymphoproliferative disorder, polymorphic type. The patient was managed with reduction in immunosuppression, rituximab therapy, and cranial radiation treatments. He had demonstrated marked improvement in his neurologic function and was ultimately discharged to inpatient rehabilitation facility.

"We Need to Deploy Them Very Thoughtfully and Carefully": Perceptions of Analytical Treatment Interruptions in HIV Cure Research in the United States-A Qualitative Inquiry.

PubMed

Dubé, Karine; Evans, David; Dee, Lynda; Sylla, Laurie; Taylor, Jeff; Skinner, Asheley; Weiner, Bryan J; Greene, Sandra B; Rennie, Stuart; Tucker, Joseph D

2018-01-01

Strategies to control HIV in the absence of antiretroviral therapy are needed to cure HIV. However, such strategies will require analytical treatment interruptions (ATIs) to determine their efficacy. We investigated how U.S. stakeholders involved in HIV cure research perceive ATIs. We conducted 36 in-depth interviews with three groups of stakeholders: 12 people living with HIV, 11 clinician-researchers, and 13 policy-makers/bioethicists. Qualitative data revealed several themes. First, there was little consensus on when ATIs would be ethically warranted. Second, the most frequent perceived hypothetical motivators for participating in research on ATIs were advancing science and contributing to society. Third, risks related to viral rebound were the most prevalent concerns related to ATIs. Stakeholders suggested ways to minimize the risks of ATIs in HIV cure research. Increased cooperation between scientists and local communities may be useful for minimizing risk. Further ethics research is necessary.

Bronchiolitis Obliterans Syndrome: The Achilles’ Heel of Lung Transplantation

PubMed Central

Weigt, S. Samuel; DerHovanessian, Ariss; Wallace, W. Dean; Lynch, Joseph P.; Belperio, John A.

2016-01-01

Lung transplantation is a therapeutic option for patients with end-stage pulmonary disorders. Unfortunately, chronic lung allograft dysfunction (CLAD), most commonly manifest as bronchiolitis obliterans syndrome (BOS), continues to be highly prevalent and is the major limitation to long-term survival. The pathogenesis of BOS is complex and involves alloimmune and nonalloimmune pathways. Clinically, BOS manifests as airway obstruction and dyspnea that are classically progressive and ultimately fatal; however, the course is highly variable, and distinguishable phenotypes may exist. There are few controlled studies assessing treatment efficacy, but only a minority of patients respond to current treatment modalities. Ultimately, preventive strategies may prove more effective at prolonging survival after lung transplantation, but their remains considerable debate and little data regarding the best strategies to prevent BOS. A better understanding of the risk factors and their relationship to the pathological mechanisms of chronic lung allograft rejection should lead to better pharmacological targets to prevent or treat this syndrome. PMID:23821508

[Peripheral facial paralysis: the role of physical medicine and rehabilitation].

PubMed

Matos, Catarina

2011-12-01

Peripheral facial paralysis (PFP) is a consequence of the peripheral neuronal lesion of the facial nerve (FN). It can be either primary (Bell`s Palsy) or secondary. The classical clinical presentation typically involves both stages of the hemiface. However, there may be other symptoms (ex. xerophthalmia, hyperacusis, phonation and deglutition changes) that one should recall. Clinical evaluation includes rigorous muscle tonus and sensibility search in the FN territory. Some useful instruments allow better objectivity in the patients' evaluation (House-Brackmann System, Facial Grading System, Functional Evaluation). There are clear referral criteria to Physical Medicine and Rehabilitation. Treatment of Bell`s Palsy may include pharmacotherapy, neuromuscular training (NMT), physical methods and surgery. In the NMT field the several treatment techniques are systematized. Therapeutic strategies should be problem-oriented and adjusted to the patient's symptoms and signs. Physical methods are reviewed. In about 15-20 % of patients permanent sequelae subside after 3 months of evolution. PFP is commonly a multidisciplinary condition. Therefore, it is important to review strategies that Physical Medicine and Rehabilitation may offer.

Reconstruction of Long Bone Infections Using the Induced Membrane Technique: Tips and Tricks.

PubMed

Mauffrey, Cyril; Hake, Mark E; Chadayammuri, Vivek; Masquelet, Alain-Charles

2016-06-01

The management of posttraumatic long bone osteomyelitis remains a challenging clinical problem. A systematic approach is necessary, beginning with eradication of the infected bone and soft tissue. There are a number of options for reconstruction of the remaining bone defect, including the induced membrane technique developed by Masquelet. We describe our technique for the 2-stage treatment of long bone osteomyelitis. The first stage involves a radical debridement, stabilization of the bone with either external fixation or an antibiotic-coated intramedullary nail, and placement of a polymethylmethacrylate spacer. The second stage includes excision of the spacer and placement of autologous bone graft. Various resection methods, fixation strategies, antibiotic additives, and types of bone grafts or substitutes can be used. The purpose of our technical article is to share our personal experience and describe several nuances that are critical for the success of this treatment strategy. Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

The coping strategies of front-line health workers in the context of user fee exemptions in Niger

PubMed Central

2015-01-01

When user fee exemptions were introduced for children under five years of age in Niger, front-line staff in the health system were not consulted in advance, and various obstacles seriously hindered the policy's implementation. Health workers developed two types of coping strategies. The first dealt with shortcomings of the policy implementation process related to management tools, drug stocks, co-existence of the fee exemption and cost recovery systems, and, above all, supply management for medicines (ordering from private companies, issuing makeshift prescriptions). The second involved clientelism, circumvention of regulations, and misappropriation of resources. Adverse effects have arisen due to both the failings of the health system and the practices of health workers. These include a focus on the commercial management of patients, the most 'costly' of whom sometimes find themselves being refused treatment, patients roaming in search of medicines and treatment, and a decline in quality of care. PMID:26558816

Quorum Quenching Mediated Approaches for Control of Membrane Biofouling

PubMed Central

Lade, Harshad; Paul, Diby; Kweon, Ji Hyang

2014-01-01

Membrane biofouling is widely acknowledged as the most frequent adverse event in wastewater treatment systems resulting in significant loss of treatment efficiency and economy. Different strategies including physical cleaning and use of antimicrobial chemicals or antibiotics have been tried for reducing membrane biofouling. Such traditional practices are aimed to eradicate biofilms or kill the bacteria involved, but the greater efficacy in membrane performance would be achieved by inhibiting biofouling without interfering with bacterial growth. As a result, the search for environmental friendly non-antibiotic antifouling strategies has received much greater attention among scientific community. The use of quorum quenching natural compounds and enzymes will be a potential approach for control of membrane biofouling. This approach has previously proven useful in diseases and membrane biofouling control by triggering the expression of desired phenotypes. In view of this, the present review is provided to give the updated information on quorum quenching compounds and elucidate the significance of quorum sensing inhibition in control of membrane biofouling. PMID:24910534

Design of pharmaceutical products to meet future patient needs requires modification of current development paradigms and business models.

PubMed

Stegemann, S; Baeyens, J-P; Becker, R; Maio, M; Bresciani, M; Shreeves, T; Ecker, F; Gogol, M

2014-06-01

Drugs represent the most common intervention strategy for managing acute and chronic medical conditions. In light of demographic change and the increasing age of patients, the classic model of drug research and development by the pharmaceutical industry and drug prescription by physicians is reaching its limits. Different stakeholders, e.g. industry, regulatory authorities, health insurance systems, physicians etc., have at least partially differing interests regarding the process of healthcare provision. The primary responsibility for the correct handling of medication and adherence to treatment schedules lies with the recipient of a drug-based therapy, i.e. the patient. It is thus necessary to interactively involve elderly patients, as well as the other stakeholders, in the development of medication and medication application devices, and in clinical trials. This approach will provide the basis for developing a strategy that better meets patients' needs, thus resulting in improved adherence to treatment schedules and better therapeutic outcomes.

Chitosan multiple addition enhances laccase production from Trametes versicolor.

PubMed

Adekunle, Abiodun Emmanuel; Wang, Feng; Hu, Jianhua; Ma, Anzhou; Guo, Chen; Zhuang, Guoqiang; Liu, Chun-Zhao

2015-10-01

Chitosan multiple addition strategy was developed to improve laccase production from Trametes versicolor cultures. The optimized multiple addition strategy was carried out by two-time addition of 0.1 g L(-1) chitosan to a 2-day-old culture media, with 24-h interval between the treatments. Under these conditions, laccase activity of 644.9 U l(-1) was achieved on the seventh day and laccase production was improved by 93.5 % higher than the control. Chitosan treatment increased reactive oxygen species generation and extracellular protein concentration in the treated mycelia. In contrast, the inducer inhibited the mycelia growth. The result of the quantitative reverse transcription polymerase chain reaction showed that the copy number of the laccase gene transcript increased by 16.7-fold in the treated mycelia relative to the control. This study provides insight into some of the intrinsic metabolic processes involved in the upregulation of laccase production in the presence of chitosan inducer in fungal culture.

Patient-oriented randomisation: A new trial design applied in the Neuroleptic Strategy Study.

PubMed

Schulz, Constanze; Timm, Jürgen; Cordes, Joachim; Gründer, Gerhard; Mühlbauer, Bernd; Rüther, Eckart; Heinze, Martin

2016-06-01

The 'gold standard' for clinical studies is a randomised controlled trial usually comparing specific treatments. If the scientific study expands to strategy comparison with each strategy including various treatments, the research problems are increasingly complicated. The strategy debate in the psychiatric community is the starting point for the development of our new design. It is widely accepted that second-generation antipsychotics are the therapy of choice in the treatment of schizophrenia. However, their general superiority over first-generation antipsychotics could not be demonstrated in recent randomised controlled trials. Furthermore, we are becoming increasingly aware that the experimental conditions of randomised controlled trials, as in the European First Episode Schizophrenia Trial and Clinical Antipsychotic Trials of Intervention Effectiveness Phase 1 studies, may be inappropriate for psychiatric treatments. The high heterogeneity in the patient population produces discrepancies between daily clinical perception and randomised controlled trials results. The patient-oriented approach in the Cost Utility of the Latest Antipsychotic drugs in Schizophrenia Study reflects everyday clinical practice. The results, however, are highly dependent on the physicians' preferences. The goal of the design described here is to take an intermediate path between randomised controlled trials and clinical studies such as Cost Utility of the Latest Antipsychotic Drugs in Schizophrenia Study, combining the advantages of both study types. The idea is to randomise two treatment pairs each consisting of one first-generation antipsychotic and one second-generation antipsychotic in a first step and subsequently, to involve the investigators in deciding for a pair most appropriate to the patients' needs and then to randomise the allocation to one drug (first-generation antipsychotic or second-generation antipsychotic) of that chosen pair. This idea was first implemented in the clinical trial, the Neuroleptic Strategy Study, with a randomised design comparing efficacy and safety of two different strategies: either to use first-generation antipsychotics (haloperidol and flupentixol) or second-generation antipsychotics (olanzapine, aripiprazole and quetiapine) in patients suffering from schizophrenia. In the course of the Neuroleptic Strategy Study, feasibility of this design was demonstrated. All aspects of the new design were implemented: randomisation process, documentation of responses from investigators as well as patients and drug logistic experience. In implementing the design, furthermore, we could investigate its theoretical properties. The physicians' preferences for specific drugs used for the respective patients were analysed. The idea of patient-oriented randomisation can be generalised. In light of the heterogeneity and complexity of patient-drug interaction, this design should prove particularly useful. © The Author(s) 2016.

A Randomized Longitudinal Factorial Design to Assess Malaria Vector Control and Disease Management Interventions in Rural Tanzania

PubMed Central

Kramer, Randall A.; Mboera, Leonard E. G.; Senkoro, Kesheni; Lesser, Adriane; Shayo, Elizabeth H.; Paul, Christopher J.; Miranda, Marie Lynn

2014-01-01

The optimization of malaria control strategies is complicated by constraints posed by local health systems, infrastructure, limited resources, and the complex interactions between infection, disease, and treatment. The purpose of this paper is to describe the protocol of a randomized factorial study designed to address this research gap. This project will evaluate two malaria control interventions in Mvomero District, Tanzania: (1) a disease management strategy involving early detection and treatment by community health workers using rapid diagnostic technology; and (2) vector control through community-supported larviciding. Six study villages were assigned to each of four groups (control, early detection and treatment, larviciding, and early detection and treatment plus larviciding). The primary endpoint of interest was change in malaria infection prevalence across the intervention groups measured during annual longitudinal cross-sectional surveys. Recurring entomological surveying, household surveying, and focus group discussions will provide additional valuable insights. At baseline, 962 households across all 24 villages participated in a household survey; 2,884 members from 720 of these households participated in subsequent malariometric surveying. The study design will allow us to estimate the effect sizes of different intervention mixtures. Careful documentation of our study protocol may also serve other researchers designing field-based intervention trials. PMID:24840349

A randomized longitudinal factorial design to assess malaria vector control and disease management interventions in rural Tanzania.

PubMed

Kramer, Randall A; Mboera, Leonard E G; Senkoro, Kesheni; Lesser, Adriane; Shayo, Elizabeth H; Paul, Christopher J; Miranda, Marie Lynn

2014-05-16

The optimization of malaria control strategies is complicated by constraints posed by local health systems, infrastructure, limited resources, and the complex interactions between infection, disease, and treatment. The purpose of this paper is to describe the protocol of a randomized factorial study designed to address this research gap. This project will evaluate two malaria control interventions in Mvomero District, Tanzania: (1) a disease management strategy involving early detection and treatment by community health workers using rapid diagnostic technology; and (2) vector control through community-supported larviciding. Six study villages were assigned to each of four groups (control, early detection and treatment, larviciding, and early detection and treatment plus larviciding). The primary endpoint of interest was change in malaria infection prevalence across the intervention groups measured during annual longitudinal cross-sectional surveys. Recurring entomological surveying, household surveying, and focus group discussions will provide additional valuable insights. At baseline, 962 households across all 24 villages participated in a household survey; 2,884 members from 720 of these households participated in subsequent malariometric surveying. The study design will allow us to estimate the effect sizes of different intervention mixtures. Careful documentation of our study protocol may also serve other researchers designing field-based intervention trials.

New Treatment Strategies of Depression: Based on Mechanisms Related to Neuroplasticity

PubMed Central

Lane, Hsien-Yuan

2017-01-01

Major depressive disorder is a severe and complex mental disorder. Impaired neurotransmission and disrupted signalling pathways may influence neuroplasticity, which is involved in the brain dysfunction in depression. Traditional neurobiological theories of depression, such as monoamine hypothesis, cannot fully explain the whole picture of depressive disorders. In this review, we discussed new treatment directions of depression, including modulation of glutamatergic system and noninvasive brain stimulation. Dysfunction of glutamatergic neurotransmission plays an important role in the pathophysiology of depression. Ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, has rapid and lasting antidepressive effects in previous studies. In addition to ketamine, other glutamatergic modulators, such as sarcosine, also show potential antidepressant effect in animal models or clinical trials. Noninvasive brain stimulation is another new treatment strategy beyond pharmacotherapy. Growing evidence has demonstrated that superficial brain stimulations, such as transcranial magnetic stimulation, transcranial direct current stimulation, cranial electrotherapy stimulation, and magnetic seizure therapy, can improve depressive symptoms. The antidepressive effect of these brain stimulations may be through modulating neuroplasticity. In conclusion, drugs that modulate neurotransmission via NMDA receptor and noninvasive brain stimulation may provide new directions of treatment for depression. Furthermore, exploring the underlying mechanisms will help in developing novel therapies for depression in the future. PMID:28491480

The current status and future potential of personalized diagnostics: Streamlining a customized process.

PubMed

Richmond, Terri D

2008-01-01

Recent genetic discoveries and related developments in genomic techniques have led to the commercialization of novel diagnostic platforms for studying disease or gauging therapeutic outcomes in individual patients. This newly emerging field is called "personalized medicine," and uses the patient's genetic composition to tailor strategies for patient-specific disease detection, treatment, or prevention. Personalized diagnostic tests are used to detect patient-to-patient variations in gene or protein expression levels, which act as indicators for drug treatments or disease prognosis. In turn, medical professionals can better answer questions such as: "Who should be treated with which drug?" and "How should the treatment be administered?" The regulations governing personalized medicine can be complicated because they encompass in vitro diagnostic systems and laboratory tests as well as methods of disease treatment and patient care. Industry, academia, medicine, and the Food and Drug Administration (FDA) are all involved in the cultivation of the field: substantial collaborations between drug developers and regulatory authorities are required to consider and shape emerging regulations as personalized drug strategies mature. Some of the regulatory issues identified by industry and the FDA about personalized medicine and personalized diagnostics will be addressed. In addition, relevant collaborations, advances, and current and draft regulatory guidances will be discussed with respect to the future of personalized medicine.

Music therapy CD creation for initial pediatric radiation therapy: a mixed methods analysis.

PubMed

Barry, Philippa; O'Callaghan, Clare; Wheeler, Greg; Grocke, Denise

2010-01-01

A mixed methods research design was used to investigate the effects of a music therapy CD (MTCD) creation intervention on pediatric oncology patients' distress and coping during their first radiation therapy treatment. The music therapy method involved children creating a music CD using interactive computer-based music software, which was "remixed" by the music therapist-researcher to extend the musical material. Eleven pediatric radiation therapy outpatients aged 6 to 13 years were randomly assigned to either an experimental group, in which they could create a music CD prior to their initial treatment to listen to during radiation therapy, or to a standard care group. Quantitative and qualitative analyses generated multiple perceptions from the pediatric patients, parents, radiation therapy staff, and music therapist-researcher. Ratings of distress during initial radiation therapy treatment were low for all children. The comparison between the two groups found that 67% of the children in the standard care group used social withdrawal as a coping strategy, compared to 0% of the children in the music therapy group; this trend approached significance (p = 0.076). MTCD creation was a fun, engaging, and developmentally appropriate intervention for pediatric patients, which offered a positive experience and aided their use of effective coping strategies to meet the demands of their initial radiation therapy treatment.

Role of the Speech-Language Pathologist (SLP) in the Head and Neck Cancer Team.

PubMed

Hansen, Kelly; Chenoweth, Marybeth; Thompson, Heather; Strouss, Alexandra

2018-01-01

While treatments for head and neck cancer are aimed at curing patients from disease, they can have significant short- and long-term negative impacts on speech and swallowing functions. Research demonstrates that early and frequent involvement of Speech-Language Pathologists (SLPs) is beneficial to these functions and overall quality of life for head and neck cancer patients. Strategies and tools to optimize communication and safe swallowing are presented in this chapter.

Contributions of in situ microscopy to the current understanding of stone biodeterioration.

PubMed

de Los Ríos, Asunción; Ascaso, Carmen

2005-09-01

In situ microscopy consists of simultaneously applying several microscopy techniques without separating the biological component from its habitat. Over the past few years, this strategy has allowed characterization of the biofilms involved in biodeterioration processes affecting stone monuments and has revealed the biogeophysical and biogeochemical impact of the microbiota present. In addition, through in situ microscopy diagnosis, appropriate treatments can be designed to resolve the problems related to microbial colonization of stone monuments.

Characterization of Prostate-Specific Membrane Antigen (PSMA) for Use in Therapeutic and Diagnostic Strategies against Prostate Cancer

DTIC Science & Technology

2000-07-01

Copenhagen, Copenhagen, Denmark To develop adjuvant therapy for glioma patients vaccination by autologous Neovascularization of blood vessels is...on the physiology of solid Vaccines : Novel Antigens and Vectors I tumors and their response to treatment. #5056 DNA VACCINATION OF BRAIN TUMOR...involvement of Mtsl(S1 0OA4) Cal’-binding protein in DNA vaccination with irradiation of tumor. The induced immunological processes tumour progression and

Strategies that Target Leukocyte Traffic in IBD: Recent Developments

PubMed Central

Rivera-Nieves, Jesús

2015-01-01

Purpose of review We review the most recent developments regarding the targeting of molecules involved in the traffic of leukocytes for the treatment of IBD. Recent Findings We discuss the most important findings of one published phase II trial that targeted the β7 integrin (Etrolizumab), two phase II trials that targeted the α4β7 integrin ligand: Mucosal Addressin Cell Adhesion Molecule-1 (MAdCAM-1, PF-00547659), a phase II targeting the chemokine IP-10 (CXCL10) in Crohn’s and a phase II trial that targeted the sphingosine-1-phosphate receptor-1 (S1P1): ozanimod in patients with ulcerative colitis (UC). Summary Targeting molecules involved in leukocyte traffic has recently become an effective and safe strategy for the treatment of IBD. Novel approaches now not only target the integrins on the lymphocyte surface, but also its endothelial ligand: MAdCAM-1. As with vedolizumab, antibodies against MAdCAM-1 appear most effective in ulcerative colitis rather than in Crohn’s. Targeting chemokines or their receptors does not appear to have the same efficacy as those that target the most stable integrin:immunoglobulin superfamily interactions between the lymphocyte and endothelium. Preliminary results also suggest that the sphingosine-1-phosphate pathway might also be targeted therapeutically in IBD, no longer with parenterally administered antibodies but with orally administered small molecules. PMID:26398681

The Cytotoxicity Mechanism of 6-Shogaol-Treated HeLa Human Cervical Cancer Cells Revealed by Label-Free Shotgun Proteomics and Bioinformatics Analysis.

PubMed

Liu, Qun; Peng, Yong-Bo; Qi, Lian-Wen; Cheng, Xiao-Lan; Xu, Xiao-Jun; Liu, Le-Le; Liu, E-Hu; Li, Ping

2012-01-01

Cervical cancer is one of the most common cancers among women in the world. 6-Shogaol is a natural compound isolated from the rhizome of ginger (Zingiber officinale). In this paper, we demonstrated that 6-shogaol induced apoptosis and G2/M phase arrest in human cervical cancer HeLa cells. Endoplasmic reticulum stress and mitochondrial pathway were involved in 6-shogaol-mediated apoptosis. Proteomic analysis based on label-free strategy by liquid chromatography chip quadrupole time-of-flight mass spectrometry was subsequently proposed to identify, in a non-target-biased manner, the molecular changes in cellular proteins in response to 6-shogaol treatment. A total of 287 proteins were differentially expressed in response to 24 h treatment with 15 μM 6-shogaol in HeLa cells. Significantly changed proteins were subjected to functional pathway analysis by multiple analyzing software. Ingenuity pathway analysis (IPA) suggested that 14-3-3 signaling is a predominant canonical pathway involved in networks which may be significantly associated with the process of apoptosis and G2/M cell cycle arrest induced by 6-shogaol. In conclusion, this work developed an unbiased protein analysis strategy by shotgun proteomics and bioinformatics analysis. Data observed provide a comprehensive analysis of the 6-shogaol-treated HeLa cell proteome and reveal protein alterations that are associated with its anticancer mechanism.

The Cytotoxicity Mechanism of 6-Shogaol-Treated HeLa Human Cervical Cancer Cells Revealed by Label-Free Shotgun Proteomics and Bioinformatics Analysis

PubMed Central

Liu, Qun; Peng, Yong-Bo; Qi, Lian-Wen; Cheng, Xiao-Lan; Xu, Xiao-Jun; Liu, Le-Le; Liu, E-Hu; Li, Ping

2012-01-01

Cervical cancer is one of the most common cancers among women in the world. 6-Shogaol is a natural compound isolated from the rhizome of ginger (Zingiber officinale). In this paper, we demonstrated that 6-shogaol induced apoptosis and G2/M phase arrest in human cervical cancer HeLa cells. Endoplasmic reticulum stress and mitochondrial pathway were involved in 6-shogaol-mediated apoptosis. Proteomic analysis based on label-free strategy by liquid chromatography chip quadrupole time-of-flight mass spectrometry was subsequently proposed to identify, in a non-target-biased manner, the molecular changes in cellular proteins in response to 6-shogaol treatment. A total of 287 proteins were differentially expressed in response to 24 h treatment with 15 μM 6-shogaol in HeLa cells. Significantly changed proteins were subjected to functional pathway analysis by multiple analyzing software. Ingenuity pathway analysis (IPA) suggested that 14-3-3 signaling is a predominant canonical pathway involved in networks which may be significantly associated with the process of apoptosis and G2/M cell cycle arrest induced by 6-shogaol. In conclusion, this work developed an unbiased protein analysis strategy by shotgun proteomics and bioinformatics analysis. Data observed provide a comprehensive analysis of the 6-shogaol-treated HeLa cell proteome and reveal protein alterations that are associated with its anticancer mechanism. PMID:23243437

Risk-benefit considerations in the treatment of relapsing-remitting multiple sclerosis

PubMed Central

Lugaresi, Alessandra; di Ioia, Maria; Travaglini, Daniela; Pietrolongo, Erika; Pucci, Eugenio; Onofrj, Marco

2013-01-01

Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system and mainly affects young adults. Its natural history has changed in recent years with the advent of disease-modifying drugs, which have been available since the early 1990s. The increasing number of first-line and second-line treatment options, together with the variable course of the disease and patient lifestyles and expectations, makes the therapeutic decision a real challenge. The aim of this review is to give a comprehensive overview of the main present and some future drugs for relapsing-remitting MS, including risk-benefit considerations, to enable readers to draw their own conclusions regarding the risk-benefit assessment of personalized treatment strategies, taking into account not only treatment-related but also disease-related risks. We performed a Medline literature search to identify studies on the treatment of MS with risk stratification and risk-benefit considerations. We focused our attention on studies of disease-modifying, immunomodulating, and immunosuppressive drugs, including monoclonal antibodies. Here we offer personal considerations, stemming from long-term experience in the treatment of MS and thorough discussions with other neurologists closely involved in the care of patients with the disease. MS specialists need to know not only the specific risks and benefits of single drugs, but also about drug interactions, either in simultaneous or serial combination therapy, and patient comorbidities, preferences, and fears. This has to be put into perspective, considering also the risks of untreated disease in patients with different clinical and radiological characteristics. There is no single best treatment strategy, but therapy has to be tailored to the patient. This is a time-consuming task, rich in complexity, and influenced by the attitude towards risk on the parts of both the patient and the clinical team. The broader the MS drug market becomes, the harder it will be for the clinician to help the patient decide which therapeutic strategy to opt for. PMID:23836975

What is the role of procedural justice in civil commitment?

PubMed

McKenna, B G; Simpson, A I; Coverdale, J H

2000-08-01

To determine best practice management strategies in the clinical application of civil commitment. All relevant literature on the topics of 'civil commitment', 'coercion' and 'procedural justice' were located on MEDLINE and PsychLIT databases and reviewed. Literature on the use of Ulysses contracts and advance directives in mental health treatment was integrated into the findings. Best practice evidence that guides management strategies is limited to the time of enactment of civil commitment. Management strategies involve enhancing the principles of procedural justice as a means of limiting negative patient perception of commitment. In the absence of evidence-based research beyond this point of enactment, grounds for the application of the principles of procedural justice are supported by reference to ethical considerations. Ulysses contracts provide an additional method for strengthening procedural justice. Procedural justice principles should be routinely applied throughout the processes of civil commitment in order to enhance longer term therapeutic outcomes and to blunt paternalism.

[A study of the value of preoperative biliary-tract drainage in the treatment of periampullary tumours: the DROP-trial].

PubMed

van der Gaag, N A; Gouma, D J

2006-03-04

Surgery in patients with obstructive jaundice caused by a periampullary (pancreas, papilla, distal bile duct) tumour is associated with a higher risk of postoperative complications than in non-jaundiced patients. Preoperative biliary drainage was introduced in an attempt to improve the general condition and thus reduce postoperative morbidity and mortality. More recently, the focus has shifted towards the negative effects of drainage, such as an increase of infectious complications. This has raised doubts as to whether biliary drainage should always be performed in these patients. The project referred to above involves a randomised multicentre trial to compare the outcome of a 'preoperative biliary-drainage strategy' (standard strategy) with that of an 'early-surgery' strategy with respect to the incidence of severe complications (primary-outcome measure), hospital stay, number of invasive diagnostic tests, costs, and quality of life.

The Brain Norepinephrine System, Stress and Cardiovascular Vulnerability

PubMed Central

Wood, Susan K.; Valentino, Rita J.

2016-01-01

Chronic exposure to psychosocial stress has adverse effects on cardiovascular health, however the stress-sensitive neurocircuitry involved remains to be elucidated. The anatomical and physiological characteristics of the locus coeruleus (LC)-norepinephrine (NE) system position it to contribute to stress-induced cardiovascular disease. This review focuses on cardiovascular dysfunction produced by social stress and a major theme highlighted is that differences in coping strategy determine individual differences in social stress-induced cardiovascular vulnerability. The establishment of different coping strategies and cardiovascular vulnerability during repeated social stress has recently been shown to parallel a unique plasticity in LC afferent regulation, resulting in either excitatory or inhibitory input to the LC. This contrasting regulation of the LC would translate to differences in cardiovascular regulation and may serve as the basis for individual differences in the cardiopathological consequences of social stress. The advances described suggest new directions for developing treatments and/or strategies for decreasing stress-induced cardiovascular vulnerability. PMID:27131968

Exploring factors influencing health-seeking decisions and retention in childhood cancer treatment programmes: perspectives of parents in Ghana.

PubMed

Renner, Lorna Awo; McGill, Deborah

2016-09-01

Developing countries such as Ghana have very poor childhood cancer survival rates. There is a need to determine reasons for late presentation and treatment abandonment which are major causes of poor survival. Understanding these issues could inform effective strategies for childhood cancer control in resource-constrained settings. To explore factors influencing parental decision-making for children with cancer in Ghana with regard to health seeking and retention in treatment, in order to provide information that will guide Public Health interventions for childhood cancer control. This exploratory qualitative study was conducted based on an interpretative epistemology using a social constructionist approach. Purposive sampling of parents attending the Paediatric Oncology Unit, Korle Bu Teaching Hospital in Accra, Ghana was undertaken. Twelve semi-structured moderate interviews and two small focus group discussions with a total of seven participants were undertaken. Data analysis was through thematic content analysis. Five major themes emerged. Knowledge and perceptions revealed a total lack of appropriate knowledge prior to diagnosis. Health-seeking behaviour was determined by interplay of individual and environmental factors. Orthodox medical treatment was largely perceived favourably. The impact of cancer on parents and children included psychological, physical and socioeconomic effects. Financial, spiritual and psychosocial support helped in coping. Parents recommended public education and health financing to address the major barriers. Broad social determinants and experiences influence parental decision making for children with cancer. This implies Health Promotion strategies with multi-sectorial involvement will be required for effective implementation of the National Strategy for Cancer Control. Funded by authors.

Implementation of a cost-effective strategy to prevent neonatal early-onset group B haemolytic streptococcus disease in the Netherlands.

PubMed

Kolkman, Diny G E; Rijnders, Marlies E B; Wouters, Maurice G A J; van den Akker-van Marle, M Elske; van der Ploeg, Cpb Kitty; de Groot, Christianne J M; Fleuren, Margot A H

2013-07-30

Early-onset Group B haemolytic streptococcus infection (EOGBS) is an important cause of neonatal morbidity and mortality in the first week of life. Primary prevention of EOGBS is possible with intra-partum antibiotic prophylaxis (IAP.) Different prevention strategies are used internationally based on identifying pregnant women at risk, either by screening for GBS colonisation and/or by identifying risk factors for EOGBS in pregnancy or labour. A theoretical cost-effectiveness study has shown that a strategy with IAP based on five risk factors (risk-based strategy) or based on a positive screening test in combination with one or more risk factors (combination strategy) was the most cost-effective approach in the Netherlands. IAP for all pregnant women with a positive culture in pregnancy (screening strategy) and treatment in line with the current Dutch guideline (IAP after establishing a positive culture in case of pre-labour rupture of membranes or preterm birth and immediate IAP in case of intra-partum fever, previous sibling with EOGBS or GBS bacteriuria), were not cost-effective. Cost-effectiveness was based on the assumption of 100% adherence to each strategy. However, adherence in daily practice will be lower and therefore have an effect on cost-effectiveness. The aims are to: a.) implement the current Dutch guideline, the risk-based strategy and the combination strategy in three pilot regions and b.) study the effects of these strategies in daily practice. Regions where all the care providers in maternity care implement the allocated strategy will be randomised. Before the introduction of the strategy, there will be a pre-test (use of the current guideline) involving 105 pregnant women per region. This will be followed by a post-test (use of the allocated strategy) involving 315 women per region. The outcome measures are: 1.) adherence to the specific prevention strategy and the determinants of adherence among care providers and pregnant women, 2.) outcomes in pregnant women and their babies and 3.) the costs of each strategy in relation to the effects. This study will provide recommendations for the implementation of the most cost-effective prevention strategy for EOGBS in the Netherlands on the basis of feasibility in daily practice. Dutch Trial Register, NTR3965.

Bisphenol A stimulates human prostate cancer cell migration via remodelling of calcium signalling.

PubMed

Derouiche, Sandra; Warnier, Marine; Mariot, Pascal; Gosset, Pierre; Mauroy, Brigitte; Bonnal, Jean-Louis; Slomianny, Christian; Delcourt, Philippe; Prevarskaya, Natalia; Roudbaraki, Morad

2013-12-01

Bisphenol A (BPA), the principal constituent of reusable water bottles, metal cans, and plastic food containers, has been shown to be involved in human prostate cancer (PCa) cell proliferation. The aim of the present study was to explore the effect of BPA on PCa cell migration and the pathways involved in these processes. Using the transwell technique, we clearly show for the first time that the pre-treatment of the cells with BPA (1-10 nM) induces human PCa cell migration. Using a calcium imaging technique, we show that BPA pre-treatment induces an amplification of Store-Operated Calcium Entry (SOCE) in LNCaP cells. RT-PCR and Western blot experiments allowed the identification of the ion channel proteins which are up-regulated by BPA pre-treatments. These include the Orai1 protein, which is known as an important SOCE actor in various cell systems, including human PCa cells. Using a siRNA strategy, we observed that BPA-induced amplification of SOCE was Orai1-dependent. Interestingly, the BPA-induced PCa cell migration was suppressed when the calcium entry was impaired by the use of SOCE inhibitors (SKF96365, BTP2), or when the extracellular calcium was chelated. Taken together, the results presented here show that BPA induces PCa cells migration via a modulation of the ion channel protein expression involved in calcium entry and in cancer cell migration. The present data provide novel insights into the molecular mechanisms involved in the effects of an environmental factor on cancer cells and suggest both the necessity of preventive measures and the possibility of targeting ion channels in the treatment of PCa cell metastasis.

Heat-Treatment-Responsive Proteins in Different Developmental Stages of Tomato Pollen Detected by Targeted Mass Accuracy Precursor Alignment (tMAPA).

PubMed

Chaturvedi, Palak; Doerfler, Hannes; Jegadeesan, Sridharan; Ghatak, Arindam; Pressman, Etan; Castillejo, Maria Angeles; Wienkoop, Stefanie; Egelhofer, Volker; Firon, Nurit; Weckwerth, Wolfram

2015-11-06

Recently, we have developed a quantitative shotgun proteomics strategy called mass accuracy precursor alignment (MAPA). The MAPA algorithm uses high mass accuracy to bin mass-to-charge (m/z) ratios of precursor ions from LC-MS analyses, determines their intensities, and extracts a quantitative sample versus m/z ratio data alignment matrix from a multitude of samples. Here, we introduce a novel feature of this algorithm that allows the extraction and alignment of proteotypic peptide precursor ions or any other target peptide from complex shotgun proteomics data for accurate quantification of unique proteins. This strategy circumvents the problem of confusing the quantification of proteins due to indistinguishable protein isoforms by a typical shotgun proteomics approach. We applied this strategy to a comparison of control and heat-treated tomato pollen grains at two developmental stages, post-meiotic and mature. Pollen is a temperature-sensitive tissue involved in the reproductive cycle of plants and plays a major role in fruit setting and yield. By LC-MS-based shotgun proteomics, we identified more than 2000 proteins in total for all different tissues. By applying the targeted MAPA data-processing strategy, 51 unique proteins were identified as heat-treatment-responsive protein candidates. The potential function of the identified candidates in a specific developmental stage is discussed.

Tumor-targeted inhibition by a novel strategy - mimoretrovirus expressing siRNA targeting the Pokemon gene.

PubMed

Tian, Zhiqiang; Wang, Huaizhi; Jia, Zhengcai; Shi, Jinglei; Tang, Jun; Mao, Liwei; Liu, Hongli; Deng, Yijing; He, Yangdong; Ruan, Zhihua; Li, Jintao; Wu, Yuzhang; Ni, Bing

2010-12-01

Pokemon gene has crucial but versatile functions in cell differentiation, proliferation and tumorigenesis. It is a master regulator of the ARF-HDM2-p53 and Rb-E2F pathways. The facts that the expression of Pokemon is essential for tumor formation and many kinds of tumors over-express the Pokemon gene make it an attractive target for therapeutic intervention for cancer treatment. In this study, we used an RNAi strategy to silence the Pokemon gene in a cervical cancer model. To address the issues involving tumor specific delivery and durable expression of siRNA, we applied the Arg-Gly-Asp (RGD) peptide ligand and polylysine (K(18)) fusion peptide to encapsulate a recombinant retrovirus plasmid expressing a siRNA targeting the Pokemon gene and produced the 'mimoretrovirus'. At charge ratio 2.0 of fusion peptide/plasmid, the mimoretrovirus formed stable and homogenous nanoparticles, and provided complete DNase I protection and complete gel retardation. This nanoparticle inhibited SiHa cell proliferation and invasion, while it promoted SiHa cell apoptosis. The binding of the nanoparticle to SiHa cells was mediated via the RGD-integrin α(v)β(3) interaction, as evidenced by the finding that unconjugated RGD peptide inhibited this binding significantly. This tumor-targeting mimoretrovirus exhibited excellent anti-tumor capacity in vivo in a nude mouse model. Moreover, the mimoretrovirus inhibited tumor growth with a much higher efficiency than recombinant retrovirus expressing siRNA or the K(18)/P4 nanoparticle lacking the RGD peptide. Results suggest that the RNAi/RGD-based mimoretrovirus developed in this study represents a novel anti-tumor strategy that may be applicable to most research involving cancer therapy and, thus, has promising potential as a cervical cancer treatment.

Long range personalized cancer treatment strategies incorporating evolutionary dynamics.

PubMed

Yeang, Chen-Hsiang; Beckman, Robert A

2016-10-22

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

Combined immunotherapy and antiangiogenic therapy of cancer with microencapsulated cells.

PubMed

Cirone, Pasquale; Bourgeois, Jacqueline M; Shen, Feng; Chang, Patricia L

2004-10-01

An alternative form of gene therapy involves immunoisolation of a nonautologous cell line engineered to secrete a therapeutic product. Encapsulation of these cells in a biocompatible polymer serves to protect these allogeneic cells from host-versus-graft rejection while recombinant products and nutrients are able to pass by diffusion. This strategy was applied to the treatment of cancer with some success by delivering either interleukin 2 or angiostatin. However, as cancer is a complex, multifactorial disease, a multipronged approach is now being developed to attack tumorigenesis via multiple pathways in order to improve treatment efficacy. A combination of immunotherapy with angiostatic therapy was investigated by treating B16-F0/neu melanoma-bearing mice with intraperitoneally implanted, microencapsulated mouse myoblasts (C2C12) genetically modified to deliver angiostatin and an interleukin 2 fusion protein (sFvIL-2). The combination treatment resulted in improved survival, delayed tumor growth, and increased histological indices of antitumor activity (apoptosis and necrosis). In addition to improved efficacy, the combination treatment also ameliorated some of the undesirable side effects from the individual treatments that have led to the previous failure of the single treatments, for example, inflammatory response to IL-2 or vascular mimicry due to angiostatin. In conclusion, the combination of immuno- and antiangiogenic therapies delivered by immunoisolated cells was superior to individual treatments for antitumorigenesis activity, not only because of their known mechanisms of action but also because of unexpected protection against the adverse side effects of the single treatments. Thus, the concept of a "cocktail" strategy, with microencapsulation delivering multiple antitumor recombinant molecules to improve efficacy, is validated.

Evidence-based medical oncology and interventional radiology paradigms for liver-dominant colorectal cancer metastases

PubMed Central

Sag, Alan Alper; Selcukbiricik, Fatih; Mandel, Nil Molinas

2016-01-01

Colorectal cancer metastasizes predictably, with liver predominance in most cases. Because liver involvement has been shown to be a major determinant of survival in this population, liver-directed therapies are increasingly considered even in cases where there is (limited) extrahepatic disease. Unfortunately, these patients carry a known risk of recurrence in the liver regardless of initial therapy choice. Therefore, there is a demand for minimally invasive, non-surgical, personalized cancer treatments to preserve quality of life in the induction, consolidation, and maintenance phases of cancer therapy. This report aims to review evidence-based conceptual, pharmacological, and technological paradigm shifts in parenteral and percutaneous treatment strategies as well as forthcoming evidence regarding next-generation systemic, locoregional, and local treatment approaches for this patient population. PMID:27003990

Addressing continuous data measured with different instruments for participants excluded from trial analysis: a guide for systematic reviewers.

PubMed

Ebrahim, Shanil; Johnston, Bradley C; Akl, Elie A; Mustafa, Reem A; Sun, Xin; Walter, Stephen D; Heels-Ansdell, Diane; Alonso-Coello, Pablo; Guyatt, Gordon H

2014-05-01

We previously developed an approach to address the impact of missing participant data in meta-analyses of continuous variables in trials that used the same measurement instrument. We extend this approach to meta-analyses including trials that use different instruments to measure the same construct. We reviewed the available literature, conducted an iterative consultative process, and developed an approach involving a complete-case analysis complemented by sensitivity analyses that apply a series of increasingly stringent assumptions about results in patients with missing continuous outcome data. Our approach involves choosing the reference measurement instrument; converting scores from different instruments to the units of the reference instrument; developing four successively more stringent imputation strategies for addressing missing participant data; calculating a pooled mean difference for the complete-case analysis and imputation strategies; calculating the proportion of patients who experienced an important treatment effect; and judging the impact of the imputation strategies on the confidence in the estimate of effect. We applied our approach to an example systematic review of respiratory rehabilitation for chronic obstructive pulmonary disease. Our extended approach provides quantitative guidance for addressing missing participant data in systematic reviews of trials using different instruments to measure the same construct. Copyright © 2014 Elsevier Inc. All rights reserved.

New avenues for improving pancreatic ductal adenocarcinoma (PDAC) treatment: Selective stroma depletion combined with nano drug delivery.

PubMed

Bhaw-Luximon, Archana; Jhurry, Dhanjay

2015-12-28

The effectiveness of chemotherapy in PDAC is hampered by the dynamic interaction between stroma and cancer cell. The two opposing schools of thought - non-depletion of the stroma vs its depletion - to better drug efficacy are here discussed. Disrupting stroma-cancer cell interaction to reduce tumor progression and promote apoptosis is identified as the new direction of treatment for PDAC. Clinical data have shown that elimination of fibrosis and blockade of the Hedgehog pathway in stroma effectively promote drug delivery to tumor site and apoptosis. Reduced stiffness of ECM, lower fibrosis, higher permeability and higher blood flow after stroma depletion increase drug delivery. Combination strategies involving selective stroma depletion coupled with chemotherapy is currently proving to be the most efficient at clinical level. Striking the right balance between fibrosis depletion and angiogenesis promotion resulting in enhanced drug delivery and apoptosis is a major challenge. The use of nano drug delivery devices coupled with stroma depletion is emerging as the next phase treatment for PDAC. The breakthrough to combat PDAC will likely be a combination of early diagnosis and the emerging chemotherapy strategies. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

PARK2-dependent mitophagy induced by acidic postconditioning protects against focal cerebral ischemia and extends the reperfusion window.

PubMed

Shen, Zhe; Zheng, Yanrong; Wu, Jiaying; Chen, Ying; Wu, Xiaoli; Zhou, Yiting; Yuan, Yang; Lu, Shousheng; Jiang, Lei; Qin, Zhenghong; Chen, Zhong; Hu, Weiwei; Zhang, Xiangnan

2017-03-04

Prompt reperfusion after cerebral ischemia is critical for neuronal survival. Any strategies that extend the limited reperfusion window will be of great importance. Acidic postconditioning (APC) is a mild acidosis treatment that involves inhaling CO 2 during reperfusion following ischemia. APC attenuates ischemic brain injury although the underlying mechanisms have not been elucidated. Here we report that APC reinforces ischemia-reperfusion-induced mitophagy in middle cortical artery occlusion (MCAO)-treated mice, and in oxygen-glucose deprivation (OGD)-treated brain slices and neurons. Inhibition of mitophagy compromises neuroprotection conferred by APC. Furthermore, mitophagy and neuroprotection are abolished in Park2 knockout mice, indicating that APC-induced mitophagy is facilitated by the recruitment of PARK2 to mitochondria. Importantly, in MCAO mice, APC treatment extended the effective reperfusion window from 2 to 4 h, and this window was further extended to 6 h by exogenously expressing PARK2. Taken together, we found that PARK2-dependent APC-induced mitophagy renders the brain resistant to ischemic injury. APC treatment could be a favorable strategy to extend the thrombolytic time window for stroke therapy.

Is screen-and-treat approach suited for screening and management of precancerous cervical lesions in Sub-Saharan Africa?

PubMed

Fokom-Domgue, Joël; Vassilakos, Pierre; Petignat, Patrick

2014-08-01

The World Health Organization guidelines for screening and management of cervical precancerous lesions updated in 2013 made an emphasis on the use of the 'screen-and-treat' approach for cervical cancer prevention. In order to facilitate scaling-up in low income settings, most of these screen-and-treat strategies do not involve confirmatory biopsy. This yields a certain rate of overtreatment. In other words, a majority of people undergoing screen-and-treat intervention who are treated does not necessarily benefit from the treatment. Therefore, the issue of potential short term and long term complications of the recommended treatment procedures (cryotherapy and Loop Electrosurgical Excision Procedure) arises. This question has seldom been studied in resource poor countries, particularly in Sub-Saharan Africa where Human Immunodeficiency Virus infection is rampant in an epidemic fashion and where the procreative capacities are socially rewarding for women. We draw the attention of the scientific community and policy makers to the fact that the lack of evidence supporting the safety of these treatment procedures in African populations may have an impact on the acceptability of these strategies and therefore on the effectiveness of screening programs. Copyright © 2014 Elsevier Inc. All rights reserved.

Future Directions for the Early Detection of Colorectal Cancer Recurrence

PubMed Central

Walker, Avery S.; Johnson, Eric K.; Maykel, Justin A.; Stojadinovic, Alex; Nissan, Aviram; Brucher, Bjorn; Champagne, Bradley J.; Steele, Scott R.

2014-01-01

Surgical resection remains a mainstay of treatment and is highly effective for localized colorectal cancer. However, ~30-40% of patients develop recurrence following surgery and 40-50% of recurrences are apparent within the first few years after initial surgical resection. Several variables factor into the ultimate outcome of these patients, including the extent of disease, tumor biology, and patient co-morbidities. Additionally, the time from initial treatment to the development of recurrence is strongly associated with overall survival, particularly in patients who recur within one year of their surgical resection. Current post-resection surveillance strategies involve physical examination, laboratory, endoscopic and imaging studies utilizing various high and low-intensity protocols. Ultimately, the goal is to detect recurrence as early as possible, and ideally in the asymptomatic localized phase, to allow initiation of treatment that may still result in cure. While current strategies have been effective, several efforts are evolving to improve our ability to identify recurrent disease at its earliest phase. Our aim with this article is to briefly review the options available and, more importantly, examine emerging and future options to assist in the early detection of colon and rectal cancer recurrence. PMID:24790655

Xanthones from Mangosteen Extracts as Natural Chemopreventive Agents: Potential Anticancer Drugs

PubMed Central

Shan, T.; Ma, Q.; Guo, K.; Liu, J.; Li, W.; Wang, F.; Wu, E.

2011-01-01

Despite decades of research, the treatment and management of malignant tumors still remain a formidable challenge for public health. New strategies for cancer treatment are being developed, and one of the most promising treatment strategies involves the application of chemopreventive agents. The search for novel and effective cancer chemopreventive agents has led to the identification of various naturally occurring compounds. Xanthones, from the pericarp, whole fruit, heartwood, and leaf of mangosteen (Garcinia mangostana Linn., GML), are known to possess a wide spectrum of pharmacologic properties, including anti-oxidant, anti-tumor, anti-allergic, anti-inflammatory, anti-bacterial, anti-fungal, and anti-viral activities. The potential chemopreventive and chemotherapeutic activities of xanthones have been demonstrated in different stages of carcinogenesis (initiation, promotion, and progression) and are known to control cell division and growth, apoptosis, inflammation, and metastasis. Multiple lines of evidence from numerous in vitro and in vivo studies have confirmed that xanthones inhibit proliferation of a wide range of human tumor cell types by modulating various targets and signaling transduction pathways. Here we provide a concise and comprehensive review of preclinical data and assess the observed anticancer effects of xanthones, supporting its remarkable potential as an anticancer agent. PMID:21902651

Topographical disorientation in a patient who never developed navigational skills: the (re)habilitation treatment.

PubMed

Incoccia, Chiara; Magnotti, Luisa; Iaria, Giuseppe; Piccardi, Laura; Guariglia, Cecilia

2009-04-01

Although many cases of topographical disorientation are described in the literature, very few attempts have been made to rehabilitate this deficit, most likely because it is a multi-faceted syndrome in which different patients are affected by different topographical deficits. Therefore, it is not easy to develop a single rehabilitation programme to improve all types of topographical disorders. We describe the rehabilitation of a young woman with selective and pervasive topographical disorientation who never developed navigational skills due to a cerebral malformation bilaterally involving the retrorolandic regions. During treatment, the patient was trained to explore her surroundings carefully, to orient herself and then to move in the environment using a language-based strategy. At the end of the treatment, the patient was able to navigate in the environment by adopting several cognitive strategies useful for orientation. This result was maintained at the one-year follow-up, at which time the patient was also able to reach locations she had never been to alone. These results suggest that even patients who have never developed the ability to orient themselves in the environment can still achieve very good functional recovery if they are accurately assessed and submitted to a specific rehabilitation intervention.

New and Emerging Treatment Options for Irritable Bowel Syndrome

PubMed Central

Lacy, Brian E.; Chey, William D.; Lembo, Anthony J.

2015-01-01

Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder associated with abdominal pain, diarrhea, constipation, or a mix of symptoms. The pathophysiology of IBS is not completely understood but appears to involve genetics, the gut microbiome, immune activation, altered intestinal permeability, and brain-gut interactions. There is no gold standard for diagnosis. Several sets of symptom-based guidelines exist. Treatment strategies for IBS may include both nonpharmacologic and pharmacologic approaches. Lifestyle modifications that aim to improve exercise, sleep, diet, and stress may be warranted. Recent data suggest that a gluten-free diet and a diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs) may benefit some patients. For patients with diarrhea-predominant IBS, treatment options include the synthetic peripheral μ-opioid receptor agonist loperamide, antispasmodic agents, antidepressants, serotonin 5-HT3 antagonists, and the gut-specific antibiotic rifaximin. Ongoing research is evaluating the use of probiotics. For patients with constipation-predominant IBS, therapeutic strategies may include dietary fiber, laxatives, and the prosecretory agents lubiprostone and linaclotide. Research is continuing to optimize the use of available agents and evaluating new approaches to further improve the care of patients with IBS. PMID:26491416

Need of righteous attitudes towards eradication of hepatitis C virus infection in Latin America.

PubMed

Panduro, Arturo; Roman, Sonia

2016-06-14

Over the last few years, we have expanded our knowledge on numerous facets of the hepatitis C virus (HCV). Beginning with its discovery and viral life cycle, its impact on health, the development of liver disease and currently, effective antiviral treatments. The latter point has become of great interest throughout the developed world, where the possible eradication of HCV through specific strategies to reach all HCV-infected people has been announced. However, this scenario is very different in the countries of Latin America (LA), in which < 2% of infected patients requiring treatment have access to HCV medications. It has been estimated that at least ten million Latin Americans may be infected with HCV. Despite the numbers, viral hepatitis does not seem to be considered a health problem in this region of the world. This reality poses a challenge for politicians and governments of these countries, as well as to the pharmaceutical industry, the medical practitioners, and academics in LA. In this editorial, we state the need for alterations in the attitudes of the integral players involved in this situation. A recognition shift could help to create preventive strategies of viral hepatitis and to advocate for accessibility to new HCV treatments.

The role of fecal microbiota transplantation in inflammatory bowel disease.

PubMed

D'Odorico, Irene; Di Bella, Stefano; Monticelli, Jacopo; Giacobbe, Daniele Roberto; Boldock, Emma; Luzzati, Roberto

2018-04-25

Increasing evidence suggests the key role of altered intestinal microbiota in the pathogenesis of inflammatory bowel disease (IBD). Management strategies involving immune modulation are effective and widely used, but treatment failures and side effects occur. Fecal microbiota transplantation (FMT) provides a novel, perhaps complementary, strategy to restore the abnormal gut microbiome in patients with IBD. This narrative review summarizes the available efficacy and safety data on the use of FMT in IBD patients. Several aspects remain to be clarified regarding clinical predictors of response to FMT, its most appropriate route of administration, and the most appropriate quantity/quality of microbiota to be transplanted. Further studies focusing on long-term outcomes and safety are also warranted. This article is protected by copyright. All rights reserved.

Physical Exercise-Induced Adult Neurogenesis: A Good Strategy to Prevent Cognitive Decline in Neurodegenerative Diseases?

PubMed Central

Yau, Suk-yu; Christie, Brian R.; So, Kwok-fai

2014-01-01

Cumulative evidence has indicated that there is an important role for adult hippocampal neurogenesis in cognitive function. With the increasing prevalence of cognitive decline associated with neurodegenerative diseases among the ageing population, physical exercise, a potent enhancer of adult hippocampal neurogenesis, has emerged as a potential preventative strategy/treatment to reduce cognitive decline. Here we review the functional role of adult hippocampal neurogenesis in learning and memory, and how this form of structural plasticity is altered in neurodegenerative diseases known to involve cognitive impairment. We further discuss how physical exercise may contribute to cognitive improvement in the ageing brain by preserving adult neurogenesis, and review the recent approaches for measuring changes in neurogenesis in the live human brain. PMID:24818140

Investigating probation strategies with juvenile offenders: the influence of officers' attitudes and youth characteristics.

PubMed

Schwalbe, Craig S; Maschi, Tina

2009-10-01

Probation officers are the focal point for most interventions with delinquent youths in the juvenile justice system. The present study examines probation strategies and interventions in a sample of 308 probation officers who completed the Probation Practices Assessment Survey (PPAS) in a web-based survey. The PPAS measures six probation approaches: deterrence, restorative justice, treatment, confrontation, counseling, and behavioral tactics. Structural equation models and latent class analyses showed that probation officers use multiple approaches with delinquent youths consistent with the balanced and restorative justice movement. Younger youths, high-risk youths, and youths with prior social service involvements are likely to receive more intensive interventions. The implications of these findings for improving probation practices with delinquent youth are discussed.

How does surgery compare with advanced intra-articular therapies in knee osteoarthritis: current thoughts

PubMed Central

Wehling, Peter; Moser, Carsten; Maixner, William

2016-01-01

The objectives of osteoarthritis (OA) management are to reduce pain and inflammation, slow cartilage degradation, improve function and reduce disability. Current strategies for managing knee OA include nonpharmacological interventions, oral pharmacological treatments, localized intra-articular injections, and surgery. It has become evident that the inflammatory response is a key contributor to the development and progression of knee OA. Signaling pathways involving growth factors and cytokines are being investigated for the development of new therapies that target the underlying biological processes causing the disease. This concept of ‘molecular orthopedics’ enables more patient-centered diagnostic and treatment strategies. In contrast to other conservative therapies, which ultimately only address OA symptoms, intra-articular injections, in particular autologous conditioned serum (ACS), provide benefits that have the potential to outweigh those of established pharmacological treatments and surgery. Surgery has historically been considered the final solution for treatment of knee OA, both by treating physicians and by patients; however, there are increasing concerns regarding the lack of randomized clinical trials providing evidence to support this opinion. Intra-articular injection of ACS has demonstrated efficacy as a treatment for knee OA in a number of studies, with a very low rate of adverse events and side effects, compared with surgery. Treatment with ACS utilizes the release of anti-inflammatory cytokines and regenerative growth factors to support the natural healing processes in the knee, and has the potential to provide a valuable alternative to surgical intervention. PMID:27247634

French consensus. Management of patients with hypersomnia: Which strategy?

PubMed

Lopez, R; Arnulf, I; Drouot, X; Lecendreux, M; Dauvilliers, Y

Central hypersomnias principally involves type 1 narcolepsy (NT1), type 2 narcolepsy (NT2) and idiopathic hypersomnia (IH). Despite great progress made in understanding the physiopathology of NT1 with low cerebrospinal fluid hypocretin-1 levels, current treatment remains symptomatic. The same applies to NT2 and IH, for which the physiopathology is still largely unknown. Controlling excessive daytime sleepiness (EDS), cataplexy, hypnagogic hallucinations, sleep paralysis and disturbed night-time sleep are key therapeutic targets in NT1. For IH and NT2, reducing EDS is the main objective. Based on European and American directives for the treatment of narcolepsy, we propose French recommendations for managing central hypersomnias as well as strategies in the case of drug-resistance. Stimulating treatments target EDS, and Modafinil is the first-line treatment. Other stimulants such as methylphenidate, pitolisant, and exceptionally dextro-amphetamine can be prescribed. Selective serotonin and noradrenaline reuptake inhibitor antidepressants are effective for the management of cataplexy in NT1. Sodium oxybate is an effective treatment for several symptoms, including EDS, cataplexy and disturbed night-time sleep. Treatment of central hypersomnia must also take into consideration frequent cardiovascular, metabolic and psychiatric comorbidities, particularly in NT1. New therapies are currently under study with the development of new stimulants and anti-cataplectics. The next few years will see innovative emerging therapies, based on a physiopathological approach, aiming to restore hypocretinergic transmission or to interrupt the autoimmune processes causing the loss of hypocretin neurons. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Motivation for change as a predictor of treatment response for dysthymia.

PubMed

Frías Ibáñez, Álvaro; González Vallespí, Laura; Palma Sevillano, Carol; Farriols Hernando, Núria

2016-05-01

Dysthymia constitutes a chronic, mild affective disorder characterized by heterogeneous treatment effects. Several predictors of clinical response and attendance have been postulated, although research on the role of the psychological variables involved in this mental disorder is still scarce. Fifty-four adult patients, who met criteria for dysthymia completed an ongoing naturalistic treatment based on the brief interpersonal psychotherapy (IPT-B), which was delivered bimonthly over 16 months. As potential predictor variables, the therapeutic alliance, coping strategies, perceived self-efficacy, and motivation for change were measured at baseline. Outcome variables were response to treatment (Clinical Global Impression and Beck’s Depression Inventory) and treatment attendance. Stepwise multiple linear regression analyses revealed that higher motivation for change predicted better response to treatment. Moreover, higher motivation for change also predicted treatment attendance. Therapeutic alliance was not a predictor variable of neither clinical response nor treatment attendance. These preliminary findings support the adjunctive use of motivational interviewing (MI) techniques in the treatment of dysthymia. Further research with larger sample size and follow-up assessment is warranted.

Generation of composite Persea americana (Mill.) (avocado) plants: A proof-of-concept-study.

PubMed

Prabhu, S Ashok; Ndlovu, Buyani; Engelbrecht, Juanita; van den Berg, Noëlani

2017-01-01

Avocado (Persea americana (Mill.)), an important commercial fruit, is severely affected by Phytophthora Root Rot in areas where the pathogen is prevalent. However, advances in molecular research are hindered by the lack of a high-throughput transient transformation system in this non-model plant. In this study, a proof-of-concept is demonstrated by the successful application of Agrobacterium rhizogenes-mediated plant transformation to produce composite avocado plants. Two ex vitro strategies were assessed on two avocado genotypes (Itzamna and A0.74): In the first approach, 8-week-old etiolated seedlings were scarred with a sterile hacksaw blade at the base of the shoot, and in the second, inch-long incisions were made at the base of the shoot (20-week-old non-etiolated plants) with a sterile blade to remove the cortical tissue. The scarred/wounded shoot surfaces were treated with A. rhizogenes strains (K599 or ARqua1) transformed with or without binary plant transformation vectors pRedRootII (DsRed1 marker), pBYR2e1-GFP (GFP- green fluorescence protein marker) or pBINUbiGUSint (GUS- beta-glucuronidase marker) with and without rooting hormone (Dip 'N' Grow) application. The treated shoot regions were air-layered with sterile moist cocopeat to induce root formation. Results showed that hormone application significantly increased root induction, while Agrobacterium-only treatments resulted in very few roots. Combination treatments of hormone+Agrobacterium (-/+ plasmids) showed no significant difference. Only the ARqua1(+plasmid):A0.74 combination resulted in root transformants, with hormone+ARqua1(+pBINUbiGUSint) being the most effective treatment with ~17 and 25% composite plants resulting from strategy-1 and strategy-2, respectively. GUS- and GFP-expressing roots accounted for less than 4 and ~11%, respectively, of the total roots/treatment/avocado genotype. The average number of transgenic roots on the composite plants was less than one per plant in all treatments. PCR and Southern analysis further confirmed the transgenic nature of the roots expressing the screenable marker genes. Transgenic roots showed hyper-branching compared to the wild-type roots but this had no impact on Phytophthora cinnamomi infection. There was no difference in pathogen load 7-days-post inoculation between transformed and control roots. Strategy-2 involving A0.74:ARqua1 combination was the best ex vitro approach in producing composite avocado plants. The approach followed in this proof-of-concept study needs further optimisation involving multiple avocado genotypes and A. rhizogenes strains to achieve enhanced root transformation efficiencies, which would then serve as an effective high-throughput tool in the functional screening of host and pathogen genes to improve our understanding of the avocado-P. cinnamomi interaction.

Generation of composite Persea americana (Mill.) (avocado) plants: A proof-of-concept-study

PubMed Central

Prabhu, S. Ashok; Ndlovu, Buyani; Engelbrecht, Juanita

2017-01-01

Avocado (Persea americana (Mill.)), an important commercial fruit, is severely affected by Phytophthora Root Rot in areas where the pathogen is prevalent. However, advances in molecular research are hindered by the lack of a high-throughput transient transformation system in this non-model plant. In this study, a proof-of-concept is demonstrated by the successful application of Agrobacterium rhizogenes-mediated plant transformation to produce composite avocado plants. Two ex vitro strategies were assessed on two avocado genotypes (Itzamna and A0.74): In the first approach, 8-week-old etiolated seedlings were scarred with a sterile hacksaw blade at the base of the shoot, and in the second, inch-long incisions were made at the base of the shoot (20-week-old non-etiolated plants) with a sterile blade to remove the cortical tissue. The scarred/wounded shoot surfaces were treated with A. rhizogenes strains (K599 or ARqua1) transformed with or without binary plant transformation vectors pRedRootII (DsRed1 marker), pBYR2e1-GFP (GFP- green fluorescence protein marker) or pBINUbiGUSint (GUS- beta-glucuronidase marker) with and without rooting hormone (Dip 'N' Grow) application. The treated shoot regions were air-layered with sterile moist cocopeat to induce root formation. Results showed that hormone application significantly increased root induction, while Agrobacterium-only treatments resulted in very few roots. Combination treatments of hormone+Agrobacterium (-/+ plasmids) showed no significant difference. Only the ARqua1(+plasmid):A0.74 combination resulted in root transformants, with hormone+ARqua1(+pBINUbiGUSint) being the most effective treatment with ~17 and 25% composite plants resulting from strategy-1 and strategy-2, respectively. GUS- and GFP-expressing roots accounted for less than 4 and ~11%, respectively, of the total roots/treatment/avocado genotype. The average number of transgenic roots on the composite plants was less than one per plant in all treatments. PCR and Southern analysis further confirmed the transgenic nature of the roots expressing the screenable marker genes. Transgenic roots showed hyper-branching compared to the wild-type roots but this had no impact on Phytophthora cinnamomi infection. There was no difference in pathogen load 7-days-post inoculation between transformed and control roots. Strategy-2 involving A0.74:ARqua1 combination was the best ex vitro approach in producing composite avocado plants. The approach followed in this proof-of-concept study needs further optimisation involving multiple avocado genotypes and A. rhizogenes strains to achieve enhanced root transformation efficiencies, which would then serve as an effective high-throughput tool in the functional screening of host and pathogen genes to improve our understanding of the avocado-P. cinnamomi interaction. PMID:29053757

The Missing Stakeholder Group: Why Patients Should be Involved in Health Economic Modelling.

PubMed

van Voorn, George A K; Vemer, Pepijn; Hamerlijnck, Dominique; Ramos, Isaac Corro; Teunissen, Geertruida J; Al, Maiwenn; Feenstra, Talitha L

2016-04-01

Evaluations of healthcare interventions, e.g. new drugs or other new treatment strategies, commonly include a cost-effectiveness analysis (CEA) that is based on the application of health economic (HE) models. As end users, patients are important stakeholders regarding the outcomes of CEAs, yet their knowledge of HE model development and application, or their involvement therein, is absent. This paper considers possible benefits and risks of patient involvement in HE model development and application for modellers and patients. An exploratory review of the literature has been performed on stakeholder-involved modelling in various disciplines. In addition, Dutch patient experts have been interviewed about their experience in, and opinion about, the application of HE models. Patients have little to no knowledge of HE models and are seldom involved in HE model development and application. Benefits of becoming involved would include a greater understanding and possible acceptance by patients of HE model application, improved model validation, and a more direct infusion of patient expertise. Risks would include patient bias and increased costs of modelling. Patient involvement in HE modelling seems to carry several benefits as well as risks. We claim that the benefits may outweigh the risks and that patients should become involved.

Development of behaviour change communication strategy for a vaccination-linked malaria control tool in southern Tanzania.

PubMed

Mushi, Adiel K; Schellenberg, Joanna; Mrisho, Mwifadhi; Manzi, Fatuma; Mbuya, Conrad; Mponda, Haji; Mshinda, Hassan; Tanner, Marcel; Alonso, Pedro; Pool, Robert; Schellenberg, David

2008-09-29

Intermittent preventive treatment of malaria in infants (IPTi) using sulphadoxine-pyrimethamine and linked to the expanded programme on immunization (EPI) is a promising strategy for malaria control in young children. As evidence grows on the efficacy of IPTi as public health strategy, information is needed so that this novel control tool can be put into practice promptly, once a policy recommendation is made to implement it. This paper describes the development of a behaviour change communication strategy to support implementation of IPTi by the routine health services in southern Tanzania, in the context of a five-year research programme evaluating the community effectiveness of IPTi. Mixed methods including a rapid qualitative assessment and quantitative health facility survey were used to investigate communities' and providers' knowledge and practices relating to malaria, EPI, sulphadoxine-pyrimethamine and existing health posters. Results were applied to develop an appropriate behaviour change communication strategy for IPTi involving personal communication between mothers and health staff, supported by a brand name and two posters. Malaria in young children was considered to be a nuisance because it causes sleepless nights. Vaccination services were well accepted and their use was considered the mother's responsibility. Babies were generally taken for vaccination despite complaints about fevers and swellings after the injections. Sulphadoxine-pyrimethamine was widely used for malaria treatment and intermittent preventive treatment of malaria in pregnancy, despite widespread rumours of adverse reactions based on hearsay and newspaper reports. Almost all health providers said that they or their spouse were ready to take SP in pregnancy (96%, 223/242). A brand name, key messages and images were developed and pre-tested as behaviour change communication materials. The posters contained public health messages, which explained the intervention itself, how and when children receive it and safety issues. Implementation of IPTi started in January 2005 and evaluation is ongoing. Behaviour Change Communication (BCC) strategies for health interventions must be both culturally appropriate and technically sound. A mixed methods approach can facilitate an interactive process among relevant actors to develop a BCC strategy.

Header: Do adult DTC programs prevent child maltreatment? Parental criminal justice involvement and children’s involvement with child protective services: Do adult drug treatment courts prevent child maltreatment?

PubMed Central

Eldred, Lindsey M.; Sloan, Frank A.; Evans, Kelly E.

2016-01-01

Background In light of evidence showing reduced criminal recidivism and cost savings, adult drug treatment courts have grown in popularity. However, the potential spillover benefits to family members are understudied. Objectives To examine: 1) the overlap between parents who were convicted of a substance-related offense and their children’s involvement with child protective services (CPS); and 2) whether parental participation in an adult drug treatment court program reduces children’s risk for CPS involvement. Methods Administrative data from North Carolina courts, birth records, and social services were linked at the child level. First, children of parents convicted of a substance-related offense were matched to (a) children of parents convicted of a non-substance-related offense and (b) those not convicted of any offense. Second, we compared children of parents who completed a DTC program with children of parents who were referred but did not enroll, who enrolled for <90 days but did not complete, and who enrolled for 90+ days but did not complete. Multivariate logistic regression was used to model group differences in the odds of being reported to CPS in the one to three years following parental criminal conviction or, alternatively, being referred to a DTC program. Results Children of parents convicted of a substance-related offense were at greater risk of CPS involvement than children whose parents were not convicted of any charge, but DTC participation did not mitigate this risk. Conclusion/Importance The role of specialty courts as a strategy for reducing children’s risk of maltreatment should be further explored. PMID:26789656

THE NGA-DOE GRANT TO EXAMINE CRITICAL ISSUES RELATED TO RADIOACTIVE WASTE AND MATERIALS DISPOSITION INVOLVING DOE FACILITIES

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

NONE

1998-04-01

Through the National Governors' Association (NGA) project ''Critical Issues Related to Radioactive Waste and Materials Disposition Involving DOE Facilities'' NGA brings together Governors' policy advisors, state regulators, and DOE officials to examine critical issues related to the cleanup and operation of DOE nuclear weapons and research facilities. Topics explored through this project include: Decisions involving disposal of mixed, low-level, and transuranic (TRU) waste and disposition of nuclear materials. Decisions involving DOE budget requests and their effect on environmental cleanup and compliance at DOE facilities. Strategies to treat mixed, low-level, and transuranic (TRU) waste and their effect on individual sites inmore » the complex. Changes to the FFCA site treatment plans as a result of proposals in DOE's Accelerating Cleanup: Paths to Closure strategy and contractor integration analysis. Interstate waste and materials shipments. Reforms to existing RCRA and CERCLA regulations/guidance to address regulatory overlap and risks posed by DOE wastes. The overarching theme of this project is to help the Department improve coordination of its major program decisions with Governors' offices and state regulators and to ensure such decisions reflect input from these key state officials and stakeholders. This report summarizes activities conducted during the quarter from December 31, 1997 through April 30, 1998 under the NGA project. The work accomplished by the NGA project team during the past four months can be categorized as follows: maintained open communication with DOE on a variety of activities and issues within the DOE environmental management complex; and provided ongoing support to state-DOE interactions in preparation for the March 30-31, 1998 NGA Federal Facilities Compliance Task Force Meeting with DOE. maintained communication with NGA Federal Facilities Compliance Task Force members regarding DOE efforts to formulate a configuration for mixed low-level waste and low-level treatment and disposal, DOE's Environmental Management Budget, and DOE's proposed Intersite Discussions.« less

THE NGA-DOE GRANT TO EXAMINE CRITICAL ISSUES RELATED TO RADIOACTIVE WASTE AND MATERIALS DISPOSITION INVOLVING DOE FACILITIES

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

NONE

1998-07-01

Through the National Governors' Association (NGA) project ''Critical Issues Related to Radioactive Waste and Materials Disposition Involving DOE Facilities'' NGA brings together Governors' policy advisors, state regulators, and DOE officials to examine critical issues related to the cleanup and operation of DOE nuclear weapons and research facilities. Topics explored through this project include: Decisions involving disposal of mixed, low-level, and transuranic (TRU) waste and disposition of nuclear materials. Decisions involving DOE budget requests and their effect on environmental cleanup and compliance at DOE facilities. Strategies to treat mixed, low-level, and transuranic (TRU) waste and their effect on individual sites inmore » the complex. Changes to the FFCA site treatment plans as a result of proposals in DOE's Accelerating Cleanup: Paths to Closure strategy and contractor integration analysis. Interstate waste and materials shipments. Reforms to existing RCRA and CERCLA regulations/guidance to address regulatory overlap and risks posed by DOE wastes. The overarching theme of this project is to help the Department improve coordination of its major program decisions with Governors' offices and state regulators and to ensure such decisions reflect input from these key state officials and stakeholders. This report summarizes activities conducted during the quarter from April 30, 1998 through June 30, 1998 under the NGA project. The work accomplished by the NGA project team during the past four months can be categorized as follows: maintained open communication with DOE on a variety of activities and issues within the DOE environmental management complex; and provided ongoing support to state-DOE interactions. maintained communication with NGA Federal Facilities Compliance Task Force members regarding DOE efforts to formulate a configuration for mixed low-level waste and low-level treatment and disposal, DOE's Environmental Management Budget, and DOE's proposed Intersite Discussions.« less

Lay Health Worker Involvement in Evidence-Based Treatment Delivery: A Conceptual Model to Address Disparities in Care.

PubMed

Barnett, Miya L; Lau, Anna S; Miranda, Jeanne

2018-05-07

Mobilizing lay health workers (LHWs) to deliver evidence-based treatments (EBTs) is a workforce strategy to address mental health disparities in underserved communities. LHWs can be leveraged to support access to EBTs in a variety of ways, from conducting outreach for EBTs delivered by professional providers to serving as the primary treatment providers. This critical review provides an overview of how LHW-supported or -delivered EBTs have been leveraged in low-, middle-, and high-income countries (HICs). We propose a conceptual model for LHWs to address drivers of service disparities, which relate to the overall supply of the EBTs provided and the demand for these treatments. The review provides illustrative case examples that demonstrate how LHWs have been leveraged globally and domestically to increase access to mental health services. It also discusses challenges and recommendations regarding implementing LHW-supported or -delivered EBTs.

Optimal treatment of laryngopharyngeal reflux disease

PubMed Central

Martinucci, Irene; Savarino, Edoardo; Nacci, Andrea; Romeo, Salvatore Osvaldo; Bellini, Massimo; Savarino, Vincenzo; Fattori, Bruno; Marchi, Santino

2013-01-01

Laryngopharyngeal reflux is defined as the reflux of gastric content into larynx and pharynx. A large number of data suggest the growing prevalence of laryngopharyngeal symptoms in patients with gastroesophageal reflux disease. However, laryngopharyngeal reflux is a multifactorial syndrome and gastroesophageal reflux disease is not the only cause involved in its pathogenesis. Current critical issues in diagnosing laryngopharyngeal reflux are many nonspecific laryngeal symptoms and signs, and poor sensitivity and specificity of all currently available diagnostic tests. Although it is a pragmatic clinical strategy to start with empiric trials of proton pump inhibitors, many patients with suspected laryngopharyngeal reflux have persistent symptoms despite maximal acid suppression therapy. Overall, there are scant conflicting results to assess the effect of reflux treatments (including dietary and lifestyle modification, medical treatment, antireflux surgery) on laryngopharyngeal reflux. The present review is aimed at critically discussing the current treatment options in patients with laryngopharyngeal reflux, and provides a perspective on the development of new therapies. PMID:24179671

Addressing Institutional Amplifiers in the Dynamics and Control of Tuberculosis Epidemics

PubMed Central

Basu, Sanjay; Stuckler, David; McKee, Martin

2011-01-01

Tuberculosis outbreaks originating in prisons, mines, or hospital wards can spread to the larger community. Recent proposals have targeted these high-transmission institutional amplifiers by improving case detection, treatment, or reducing the size of the exposed population. However, what effects these alternative proposals may have is unclear. We mathematically modeled these control strategies and found case detection and treatment methods insufficient in addressing epidemics involving common types of institutional amplifiers. Movement of persons in and out of amplifiers fundamentally altered the transmission dynamics of tuberculosis in a manner not effectively mitigated by detection or treatment alone. Policies increasing the population size exposed to amplifiers or the per-person duration of exposure within amplifiers potentially worsened incidence, even in settings with high rates of detection and treatment success. However, reducing the total population size entering institutional amplifiers significantly lowered tuberculosis incidence and the risk of propagating new drug-resistant tuberculosis strains. PMID:21212197

A control systems engineering approach for adaptive behavioral interventions: illustration with a fibromyalgia intervention.

PubMed

Deshpande, Sunil; Rivera, Daniel E; Younger, Jarred W; Nandola, Naresh N

2014-09-01

The term adaptive intervention has been used in behavioral medicine to describe operationalized and individually tailored strategies for prevention and treatment of chronic, relapsing disorders. Control systems engineering offers an attractive means for designing and implementing adaptive behavioral interventions that feature intensive measurement and frequent decision-making over time. This is illustrated in this paper for the case of a low-dose naltrexone treatment intervention for fibromyalgia. System identification methods from engineering are used to estimate dynamical models from daily diary reports completed by participants. These dynamical models then form part of a model predictive control algorithm which systematically decides on treatment dosages based on measurements obtained under real-life conditions involving noise, disturbances, and uncertainty. The effectiveness and implications of this approach for behavioral interventions (in general) and pain treatment (in particular) are demonstrated using informative simulations.

Model to Determine the Optimal Dietary Elimination Strategy for Treatment of Eosinophilic Esophagitis.

PubMed

Zhan, Tiannan; Ali, Ayman; Choi, Jin G; Lee, Minyi; Leung, John; Dellon, Evan S; Garber, John J; Hur, Chin

2018-05-03

Elimination diets are effective treatments for eosinophilic esophagitis (EoE), but foods that activate esophagitis are identified empirically, via a process that involves multiple esophagogastroduodenoscopies (EGDs). No optimized approach has been developed to identify foods that activate EoE. We aimed to compare clinical strategies to provide data to guide treatment. We developed a computer-based simulation model to determine the optimal empiric elimination strategy based on reported prevalence values for foods that activate EoE. These were identified in a systematic review, searching PubMed through October 1, 2017 for prospective and retrospective studies of EoE and diet. Each patient in our virtual cohort was assigned profile comprising as many as 12 foods known to induce EoE, including dairy, wheat, eggs, soy, nuts, seafood, beef, corn, chicken, potato, pork, and/or rice. To balance the strategy success rate with the number of EGDs required for food identification, we applied an efficiency frontier approach. Strategies on the frontier were the most efficient, requiring fewer EGDs for higher or equivalent success rates relative to their comparable, neighboring strategies. In all simulations, we found the 1,4,8-food and 1,3-food strategies to be the most efficient in identifying foods that induce EoE, resulting in the highest rate of the correct identification of food triggers balanced by the number of EGDs required to complete the food elimination strategy. Both strategies begin with elimination of dairy; if EoE remission is not achieved, the 1,3 diet proceeds to eliminate wheat and eggs in addition to dairy, and the 1,4,8 strategy removes wheat, eggs, dairy, and soy. In the case of persistent EoE after the second round of food elimination, the 1,3-food strategy terminates, whereas the 1,4,8-food diet eliminates corn, chicken, beef, and pork. The 1,4,8-food resulted in correct identification of foods that activated esophagitis in 76.68% of patients, with a mean 4.13 EGDs and a median 6 EGDs. The 1,3-food strategy identified foods that activated esophagitis in 42.76% of patients, with a mean of 3.36 EGDs and a median 2 EGDs required. In a modeling analysis, we found the 1,4,8-food and 1,3-food elimination strategies to be the most efficient in detection of foods that induce EoE in patients, the 1,4,8-food strategy was optimal, requiring a mean of only 4.13 EGDs for food identification. However, the ideal elimination strategy will vary based on clinical priorities. Additional research on specific foods that induce EoE are needed to confirm the predictions of this model. Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.

Depth of Cervical Intraepithelial Neoplasia Grade 3 in Peruvian Women: Implications for Therapeutic Depth of Necrosis.

PubMed

Taxa, Luis; Jeronimo, Jose; Alonzo, Todd A; Gage, Julia; Castle, Philip E; Cremer, Miriam L; Felix, Juan C

2018-01-01

To determine the involvement of cervical intraepithelial neoplasia grade 3 (CIN3) in a population of women in a lower-resource setting. One hundred twelve consecutive cone excision specimens with histological diagnosis of CIN3 were retrieved from the National Institute of Neoplastic Diseases in Lima Peru. Two pathologists independently evaluated each specimen microscopically and confirmed 107 cases that could be measured by optical micrometry. Depth and breadth of the lesions were measured microscopically. The mean maximal depth of cervical involvement by CIN3 was 2 ± 0.13 mm; depth was less than 3.5 mm in 89.7% of cases and less than 5 mm in 93.5%. Mean breadth of CIN3 was 7.3 ± 4.4 mm; breadth was less than 15.9 mm in 95% of cases and less than 20.5 mm in 99.7%. The correlation coefficient between breadth and depth of CIN3 was 0.61. No significant correlation was found between age and depth. Depth of CIN3 involvement in a developing country is significantly deeper than that reported in the United States. Treatment selection for women with CIN3 and risk of treatment failure may vary between developing and developed countries because of the difference in the depth of lesions. Countries with underscreened populations need to consider the increased disease severity in devising treatment strategies.

Risk-adapted, long-term management in childhood-onset craniopharyngioma.

PubMed

Müller, Hermann L

2017-04-01

This report is a review of findings on the diagnosis, treatment, clinical course, follow-up, and prognosis of craniopharyngioma patients with special regard to clinical trials and long-term management. Literature search on Pubmed for paper published after 1994. Craniopharyngiomas are rare, embryonic malformations of the sellar/parasellar region with low histological grade. Clinical manifestations are related to increased intracranial pressure, visual impairment, and hypothalamic/pituitary deficiencies. If the tumor is favorably localized, therapy of choice is complete resection, with care taken to preserve hypothalamic and optic functions. In patients with unfavorable tumor location (i.e. involvement of hypothalamic areas), recommended therapy is limited hypothalamus-sparing surgical strategy followed by irradiation. Irradiation has proven effective in treatment of recurrences and progression. Surgical lesions and/or anatomical involvement of posterior hypothalamic areas can result in serious sequelae, mainly hypothalamic syndrome. It is crucial that craniopharyngioma be managed as a frequently chronic disease, providing ongoing care of pediatric and adult patients' by experienced multidisciplinary teams in the context of multicenter trials.

Complementary and alternative medical therapies for interstitial cystitis: an update from the United States

PubMed Central

Atchley, Megan Danielle; Shah, Nima M.

2015-01-01

The diagnosis and treatment of interstitial cystitis/bladder pain syndrome (IC/BPS) has shifted from organ-specific to a multifactorial, multidisciplinary and individualized approach. Patients with refractory and debilitating symptoms may respond to complementary and alternative medical treatments (CAM). Through CAM therapies, practitioners assist the patient to be at the center of their care, empowering them to be emotionally and physically involved. Multi-disciplinary care, including urology, gynecology, gastroenterology, neurology, psychology, physiotherapy and pain medicine, is also identified to be the crux of adequate management of patients with chronic pelvic pain because of its variable etiology. The purpose of this review is to emphasize these changes and discuss management strategies. PMID:26816868

Complementary and alternative medical therapies for interstitial cystitis: an update from the United States.

PubMed

Atchley, Megan Danielle; Shah, Nima M; Whitmore, Kristene E

2015-12-01

The diagnosis and treatment of interstitial cystitis/bladder pain syndrome (IC/BPS) has shifted from organ-specific to a multifactorial, multidisciplinary and individualized approach. Patients with refractory and debilitating symptoms may respond to complementary and alternative medical treatments (CAM). Through CAM therapies, practitioners assist the patient to be at the center of their care, empowering them to be emotionally and physically involved. Multi-disciplinary care, including urology, gynecology, gastroenterology, neurology, psychology, physiotherapy and pain medicine, is also identified to be the crux of adequate management of patients with chronic pelvic pain because of its variable etiology. The purpose of this review is to emphasize these changes and discuss management strategies.

Successfully Treated Calcific Uremic Arteriolopathy: Two Cases of a High Anion Gap Metabolic Acidosis with Intravenous Sodium Thiosulfate

PubMed Central

Rein, Joshua L.; Miyata, Kana N.; Dadzie, Kobena A.; Gruber, Steven J.; Sulica, Roxana; Winchester, James F.

2014-01-01

Calcific uremic arteriolopathy (CUA) is a rare and potentially fatal disorder of calcification involving subcutaneous small vessels and fat in patients with renal insufficiency. We describe the successful use of intravenous sodium thiosulfate (STS) for the treatment of CUA in two patients. The first case was complicated by the development of a severe anion gap metabolic acidosis, which was accompanied by a seizure. Both patients had complete wound healing within five months. Although STS should be considered in the treatment of CUA, little is known about pharmacokinetics and additional studies are required to determine dosing strategies to minimize severe potential side effects. PMID:25506005

Rapid control of a chancroid outbreak: implications for Canada.

PubMed Central

Jessamine, P G; Brunham, R C

1990-01-01

From June to November 1987 an outbreak of chancroid occurred in Winnipeg, the first in more than 10 years; 14 people (9 men, 5 women) were involved. Nine of the cases were confirmed through culture. A control strategy was implemented in November 1987 that included presumptive treatment of genital ulcer disease with single-dose antimicrobial therapy, intensive tracing of contacts and treatment of asymptomatic sexual contacts. The origin of the outbreak was not determined, and an epidemiologic link between all the patients could not be demonstrated. The isolates were found to contain the same plasmid; this suggested that a single clone of Haemophilus ducreyi was responsible for the outbreak. Images Fig. 2 PMID:2337844

Management of Acute Exacerbation of Asthma and Chronic Obstructive Pulmonary Disease in the Emergency Department.

PubMed

Suau, Salvador J; DeBlieux, Peter M C

2016-02-01

Acute asthma and chronic obstructive pulmonary disease (COPD) exacerbations are the most common respiratory diseases requiring emergent medical evaluation and treatment. Asthma and COPD are chronic, debilitating disease processes that have been differentiated traditionally by the presence or absence of reversible airflow obstruction. Asthma and COPD exacerbations impose an enormous economic burden on the US health care budget. In daily clinical practice, it is difficult to differentiate these 2 obstructive processes based on their symptoms, and on their nearly identical acute treatment strategies; major differences are important when discussing anatomic sites involved, long-term prognosis, and the nature of inflammatory markers. Copyright © 2016 Elsevier Inc. All rights reserved.

Diagnosis and management of hemangiomas and vascular malformations of the head and neck.

PubMed

Buckmiller, L M; Richter, G T; Suen, J Y

2010-07-01

Vascular anomalies are congenital errors in vascular development. They frequently involve the head, neck, and oral cavity. Subdivided into vascular tumors (hemangiomas) and vascular malformations, vascular anomalies remain poorly understood. However, growing interest and recent advances in the diagnosis, management, and molecular characterization of these lesions are improving treatment strategies. The role of the multidisciplinary team cannot be overstated. This review provides both basic and up-to-date knowledge on the most common vascular anomalies encountered by physicians and practitioners. Because treatment options for vascular anomalies are widely variable and often debated, this report aims to provide a comprehensive approach to these lesions based upon current concepts and practical clinical experience.

Tailored central nervous system-directed treatment strategy for isolated CNS recurrence of adult acute myeloid leukemia.

PubMed

Zheng, Changcheng; Liu, Xin; Zhu, Weibo; Cai, Xiaoyan; Wu, Jingsheng; Sun, Zimin

2014-06-01

The aim of this report was to investigate the tailored treatment strategies for isolated central nervous system (CNS) recurrence in adult patients with acute myeloid leukemia (AML). Isolated CNS recurrence was documented in 34 patients: there were 18, 6, and 10 patients with meningeal involvement type (type A), cranial nerve palsy type (type B), and myeloid sarcoma type (type C), respectively. For patients with type A, intrathecal chemotherapy was the predominant strategy. For type B, systemic HD-Ara-C with four cycles was the main treatment. For type C, cranial irradiation or craniospinal irradiation was adopted and two cycles of HD-Ara-C were given after the irradiation. The 5-year cumulative incidence of CNS recurrence was 12.8%. There was a significantly higher WBC count (32.6∼60.8 × 10(9)/l) in patients at first diagnosis who developed CNS recurrence (all of the three types) compared with patients with no CNS recurrence (10.1 × 10(9)/l) (P = 0.005). We found that a significantly more patients with AML-M5 and 11q23 abnormalities developed CNS recurrence in type A (P < 0.001, 0.005). Twenty-four out of 34 patients (70.6%) with CNS recurrence achieved CNS complete remission at a median of 58 days (range, 30-120). The 3-year disease-free survival and overall survival estimates for all CNS recurrence patients were 21.6 and 25.3%, respectively. This report indicates that the tailored CNS-directed strategy is an effective modality to treat CNS recurrence in adult AML, but further studies are needed to improve the long-term survival.

Canine Models for Copper Homeostasis Disorders.

PubMed

Wu, Xiaoyan; Leegwater, Peter A J; Fieten, Hille

2016-02-04

Copper is an essential trace nutrient metal involved in a multitude of cellular processes. Hereditary defects in copper metabolism result in disorders with a severe clinical course such as Wilson disease and Menkes disease. In Wilson disease, copper accumulation leads to liver cirrhosis and neurological impairments. A lack in genotype-phenotype correlation in Wilson disease points toward the influence of environmental factors or modifying genes. In a number of Non-Wilsonian forms of copper metabolism, the underlying genetic defects remain elusive. Several pure bred dog populations are affected with copper-associated hepatitis showing similarities to human copper metabolism disorders. Gene-mapping studies in these populations offer the opportunity to discover new genes involved in copper metabolism. Furthermore, due to the relatively large body size and long life-span of dogs they are excellent models for development of new treatment strategies. One example is the recent use of canine organoids for disease modeling and gene therapy of copper storage disease. This review addresses the opportunities offered by canine genetics for discovery of genes involved in copper metabolism disorders. Further, possibilities for the use of dogs in development of new treatment modalities for copper storage disorders, including gene repair in patient-derived hepatic organoids, are highlighted.

Canine Models for Copper Homeostasis Disorders

PubMed Central

Wu, Xiaoyan; Leegwater, Peter A. J.; Fieten, Hille

2016-01-01

Copper is an essential trace nutrient metal involved in a multitude of cellular processes. Hereditary defects in copper metabolism result in disorders with a severe clinical course such as Wilson disease and Menkes disease. In Wilson disease, copper accumulation leads to liver cirrhosis and neurological impairments. A lack in genotype-phenotype correlation in Wilson disease points toward the influence of environmental factors or modifying genes. In a number of Non-Wilsonian forms of copper metabolism, the underlying genetic defects remain elusive. Several pure bred dog populations are affected with copper-associated hepatitis showing similarities to human copper metabolism disorders. Gene-mapping studies in these populations offer the opportunity to discover new genes involved in copper metabolism. Furthermore, due to the relatively large body size and long life-span of dogs they are excellent models for development of new treatment strategies. One example is the recent use of canine organoids for disease modeling and gene therapy of copper storage disease. This review addresses the opportunities offered by canine genetics for discovery of genes involved in copper metabolism disorders. Further, possibilities for the use of dogs in development of new treatment modalities for copper storage disorders, including gene repair in patient-derived hepatic organoids, are highlighted. PMID:26861285

The role of stress and beta-adrenergic system in melanoma: current knowledge and possible therapeutic options.

PubMed

Colucci, Roberta; Moretti, Silvia

2016-05-01

The aim of the present review was to discuss recent findings on the role of beta-adrenergic system in melanoma, in order to provide information on the biological responses elicited by its activation and its potential application for melanoma treatment. A literature search was performed, and evidences regarding the involvement of stress and beta-adrenergic system in cancer and melanoma were found and discussed. Our search pointed out that beta-adrenergic system is a key regulator of important biological processes involved in the onset and progression of some solid tumors. In the last decade, functional beta-adrenoceptors have been also identified on melanoma cells, as well as on their microenvironment cells. Similarly to other common cancers too, the activation of such adrenoceptors by catecholamines, usually released under stress conditions, has been found to trigger pro-tumorigenic pathways contributing to cell proliferation and motility, immune system regulation, apoptosis, epithelial-mesenchymal transition, invasion and neoangiogenesis. The biological evidences we found clarify and sustain the clinical evidences reporting the involvement of chronic stress in melanoma onset and progression. In such scenario, it is conceivable that a therapeutic approach targeting beta-adrenergic system could constitute a novel and promising strategy for melanoma treatment.

Guidelines for the management of neuroendocrine tumours by the Brazilian gastrointestinal tumour group

PubMed Central

Riechelmann, Rachel P; Weschenfelder, Rui F; Costa, Frederico P; Andrade, Aline Chaves; Osvaldt, Alessandro Bersch; Quidute, Ana Rosa P; dos Santos, Allan; Hoff, Ana Amélia O; Gumz, Brenda; Buchpiguel, Carlos; Vilhena Pereira, Bruno S; Lourenço Junior, Delmar Muniz; da Rocha Filho, Duilio Reis; Fonseca, Eduardo Antunes; Riello Mello, Eduardo Linhares; Makdissi, Fabio Ferrari; Waechter, Fabio Luiz; Carnevale, Francisco Cesar; Coura-Filho, George B; de Paulo, Gustavo Andrade; Girotto, Gustavo Colagiovanni; Neto, João Evangelista Bezerra; Glasberg, João; Casali-da-Rocha, Jose Claudio; Rego, Juliana Florinda M; de Meirelles, Luciana Rodrigues; Hajjar, Ludhmila; Menezes, Marcos; Bronstein, Marcello D; Sapienza, Marcelo Tatit; Fragoso, Maria Candida Barisson Villares; Pereira, Maria Adelaide Albergaria; Barros, Milton; Forones, Nora Manoukian; do Amaral, Paulo Cezar Galvão; de Medeiros, Raphael Salles Scortegagna; Araujo, Raphael L C; Bezerra, Regis Otaviano França; Peixoto, Renata D’Alpino; Aguiar, Samuel; Ribeiro, Ulysses; Pfiffer, Tulio; Hoff, Paulo M; Coutinho, Anelisa K

2017-01-01

Neuroendocrine tumours are a heterogeneous group of diseases with a significant variety of diagnostic tests and treatment modalities. Guidelines were developed by North American and European groups to recommend their best management. However, local particularities and relativisms found worldwide led us to create Brazilian guidelines. Our consensus considered the best feasible strategies in an environment involving more limited resources. We believe that our recommendations may be extended to other countries with similar economic standards. PMID:28194228

Sarcoidosis extent relates to molecular variability.

PubMed

Monast, C S; Li, K; Judson, M A; Baughman, R P; Wadman, E; Watt, R; Silkoff, P E; Barnathan, E S; Brodmerkel, C

2017-06-01

The molecular basis of sarcoidosis phenotype heterogeneity and its relationship to effective treatment of sarcoidosis have not been elucidated. Peripheral samples from sarcoidosis subjects who participated in a Phase II study of golimumab [anti-tumour necrosis factor (TNF)-α] and ustekinumab [anti-interleukin (IL)-12p40] were used to measure the whole blood transcriptome and levels of serum proteins. Differential gene and protein expression analyses were used to explore the molecular differences between sarcoidosis phenotypes as defined by extent of organ involvement. The same data were also used in conjunction with an enrichment algorithm to identify gene expression changes associated with treatment with study drugs compared to placebo. Our analyses revealed marked heterogeneity among the three sarcoidosis phenotypes included in the study cohort, including striking differences in enrichment of the interferon pathway. Conversely, enrichments of multiple pathways, including T cell receptor signalling, were similar among phenotypes. We also identify differences between treatment with golimumab and ustekinumab that may explain the differences in trends for clinical efficacy observed in the trial. We find that molecular heterogeneity is associated with sarcoidosis in a manner that may be related to the extent of organ involvement. These findings may help to explain the difficulty in identifying clinically efficacious sarcoidosis treatments and suggest hypotheses for improved therapeutic strategies. © 2017 British Society for Immunology.

Therapies targeting cancer stem cells: Current trends and future challenges

PubMed Central

Dragu, Denisa L; Necula, Laura G; Bleotu, Coralia; Diaconu, Carmen C; Chivu-Economescu, Mihaela

2015-01-01

Traditional therapies against cancer, chemo- and radiotherapy, have multiple limitations that lead to treatment failure and cancer recurrence. These limitations are related to systemic and local toxicity, while treatment failure and cancer relapse are due to drug resistance and self-renewal, properties of a small population of tumor cells called cancer stem cells (CSCs). These cells are involved in cancer initiation, maintenance, metastasis and recurrence. Therefore, in order to develop efficient treatments that can induce a long-lasting clinical response preventing tumor relapse it is important to develop drugs that can specifically target and eliminate CSCs. Recent identification of surface markers and understanding of molecular feature associated with CSC phenotype helped with the design of effective treatments. In this review we discuss targeting surface biomarkers, signaling pathways that regulate CSCs self-renewal and differentiation, drug-efflux pumps involved in apoptosis resistance, microenvironmental signals that sustain CSCs growth, manipulation of miRNA expression, and induction of CSCs apoptosis and differentiation, with specific aim to hamper CSCs regeneration and cancer relapse. Some of these agents are under evaluation in preclinical and clinical studies, most of them for using in combination with traditional therapies. The combined therapy using conventional anticancer drugs with CSCs-targeting agents, may offer a promising strategy for management and eradication of different types of cancers. PMID:26516409

Qualitative analysis of social network influences on quitting smoking among individuals with serious mental illness.

PubMed

Aschbrenner, Kelly A; Naslund, John A; Gill, Lydia; Hughes, Terence; O'Malley, Alistair J; Bartels, Stephen J; Brunette, Mary F

2017-07-04

The prevalence of cigarette smoking among adults with serious mental illness (SMI) remains high in the United States despite the availability of effective smoking cessation treatment. Identifying social influences on smoking and smoking cessation may help enhance intervention strategies to help smokers with SMI quit. The objective of this qualitative study was to explore social network influences on efforts to quit smoking among adults with SMI enrolled in a cessation treatment program. Participants were 41 individuals with SMI enrolled in a Medicaid Demonstration Project of smoking cessation at community mental health centers. A convenience sampling strategy was used to recruit participants for social network interviews exploring the influence of family, friends, peers, and significant others on quitting smoking. A team-based analysis of qualitative data involved descriptive coding, grouping coded data into categories, and identifying themes across the data. Social barriers to quitting smoking included pro-smoking social norms, attitudes, and behaviors of social network members, and negative interactions with network members, either specific to smoking or that triggered smoking. Social facilitators to quitting included quitting with network members, having cessation role models, and social support for quitting from network members. Similar to the general population, social factors appear to influence efforts to quit smoking among individuals with SMI enrolled in cessation treatment. Interventions that leverage positive social influences on smoking cessation have the potential to enhance strategies to help individuals with SMI quit smoking.

[Treatment strategy and planning for pilon fractures].

PubMed

Mittlmeier, Thomas; Wichelhaus, Alice

2017-08-01

Pilon fractures are mainly severe and prognostically serious injuries with a high rate of relevant soft tissue involvement. The adequate decision making and choice of treatment in the early phase of trauma are of paramount importance for the final outcome. This essentially encompasses the management of the soft tissue damage, the surgical planning and the differentiated selection of procedures. Most concepts of staged treatment nowadays offer a wide range of options which are integrated into expert-based algorithms. The aim of the present analysis was to display the strategy variations for the treatment of pilon fractures taking into account the advantages and disadvantages of the corresponding treatment concepts. A staged procedure including primary closed reduction employing ligamentotaxis and fixation of the joints of the hindfoot via tibiocalcaneal metatarsal fixation offers a safe basis for consecutive imaging and the selection of specific approaches for definitive reconstruction. A simultaneous reconstruction and fixation of the fibula during the primary intervention are generally not recommended in order to avoid any limitations for subsequent reconstructive procedures. A time frame for definitive reconstruction covers a period of up to 3 weeks after trauma and allows a detailed planning considering the individual dynamics of the soft tissue situation and any logistic requirements. For the choice of the definitive treatment concept a wide range of procedures and implants are available. There are also valid concepts for primary treatment of defined fracture constellations while primary arthrodesis represents a solution in cases of major destruction of the joint surface. Knowledge of the multiple procedural variations for pilon fracture treatment creates the basis to optimize the treatment modalities and to take into account individual parameters of the fracture.

From Persuasion to Coercion: Responding to the Reluctant Patient in Rehabilitation.

PubMed

Anderson, Lynley; Delany, Clare

2016-08-01

Early mobilization of patients while in hospital has been demonstrated to provide better outcomes for patients and use fewer resources. Physical therapy-based rehabilitation is central to achieving those goals. Successful rehabilitation requires that patient's and therapist's goals align, and this is commonly the case. However, occasionally, physical therapists will come across patients who are competent but reluctant to mobilize. This situation leaves the physical therapist in an ethical quandary: either accept the patient's right to refuse proposed treatment or utilize other strategies to encourage the patient to adhere to treatment. Practically, physical therapists will use a range of treatment pressures, including persuasion, offering incentives, inducements, possibly threatening or coercing, and even explicitly overriding the patient's wishes (compulsion). Deciding which treatment pressure is ethically acceptable involves the physical therapist balancing his or her therapeutic view of what is in a patient's best interests against the therapist's ethical responsibility to respect patient autonomy. This article evaluates some common strategies used by physical therapists to influence, persuade, or perhaps pressure patients to adhere to rehabilitation. The work of Szmukler and Appelbaum is utilized in analyzing treatment pressures. The authors conclude that there is a spectrum of treatment pressures, with some (persuasion and incentives) being more acceptable than others (threats and compulsion). As physical therapists balance health system pressures for rapid turnover of beds with obligations to benefit patients within limited reimbursement models, while respecting the patients' autonomy, they must be mindful of the effects of treatment pressure on patient care. © 2016 American Physical Therapy Association.

What Are the Top 10 Research Questions in the Treatment of Inflammatory Bowel Disease? A Priority Setting Partnership with the James Lind Alliance.

PubMed

Hart, Ailsa L; Lomer, Miranda; Verjee, Azmina; Kemp, Karen; Faiz, Omar; Daly, Ann; Solomon, Julie; McLaughlin, John

2017-02-01

Many uncertainties remain regarding optimal therapies and strategies for the treatment of inflammatory bowel disease. Setting research priorities addressing therapies requires a partnership between health care professionals, patients and organisations supporting patients. We aimed to use the structure of the James Lind Alliance Priority Setting Partnership, which has been used in other disease areas, to identify and prioritise unanswered questions about treatments for inflammatory bowel disease. The James Lind Priority Setting Partnership uses methods agreed and adopted in other disease areas to work with patients and clinicians: to identify uncertainties about treatments; to agree by consensus a prioritised list of uncertainties for research; then to translate these uncertainties into research questions which are amenable to hypothesis testing; and finally to take results to research commissioning bodies to be considered for funding. A total of 1636 uncertainties were collected in the initial survey from 531 respondents, which included 22% health care professionals and 78% patients and carers. Using the rigorously applied processes of the priority setting partnership, this list was distilled down to the top 10 research priorities for inflammatory bowel disease. The top priorities were: identifying treatment strategies to optimise efficacy, safety and cost-effectiveness; and stratifying patients with regard to their disease course and treatment response. Diet and symptom control [pain, incontinence and fatigue] were also topics which were prioritised. A partnership involving multidisciplinary clinicians, patients and organisations supporting patients has identified the top 10 research priorities in the treatment of patients with inflammatory bowel disease. © European Crohn’s and Colitis Organisation 2016.

Pharmacotherapy for alcohol dependence: perceived treatment barriers and action strategies among Veterans Health Administration service providers.

PubMed

Harris, Alex H S; Ellerbe, Laura; Reeder, Rachelle N; Bowe, Thomas; Gordon, Adam J; Hagedorn, Hildi; Oliva, Elizabeth; Lembke, Anna; Kivlahan, Daniel; Trafton, Jodie A

2013-11-01

Although access to and consideration of pharmacological treatments for alcohol dependence are consensus standards of care, receipt of these medications by patients is generally rare and highly variable across treatment settings. The goal of the present project was to survey and interview the clinicians, managers, and pharmacists affiliated with addiction treatment programs within Veterans Health Administration (VHA) facilities to learn about their perceptions of barriers and facilitators regarding greater and more reliable consideration of pharmacological treatments for alcohol dependence. Fifty-nine participants from 19 high-adopting and 11 low-adopting facilities completed the survey (facility-level response rate = 50%) and 23 participated in a structured interview. The top 4 barriers to increased consideration and use of pharmacotherapy for alcohol dependence were consistent across high- and low-adopting facilities and included perceived low patient demand, pharmacy procedures or formulary restrictions, lack of provider skills or knowledge regarding pharmacotherapy for alcohol dependence, and lack of confidence in treatment effectiveness. Low patient demand was rated as the most important barrier for oral naltrexone and disulfiram, whereas pharmacy or formulary restrictions were rated as the most important barrier for acamprosate and extended-release naltrexone. The 4 strategies rated across low- and high-adopting facilities as most likely to facilitate consideration and use of pharmacotherapy for alcohol dependence were more education to patients about existing medications, more education to health care providers about medications, increased involvement of physicians in treatment for alcohol dependence, and more compelling research on existing medications. This knowledge provides a foundation for designing, deploying, and evaluating targeted implementation efforts.

Restoring functional neurofibromin by protein transduction.

PubMed

Mellert, K; Lechner, S; Lüdeke, M; Lamla, M; Möller, P; Kemkemer, R; Scheffzek, K; Kaufmann, D

2018-04-18

In Neurofibromatosis 1 (NF1) germ line loss of function mutations result in reduction of cellular neurofibromin content (NF1+/-, NF1 haploinsufficiency). The Ras-GAP neurofibromin is a very large cytoplasmic protein (2818 AA, 319 kDa) involved in the RAS-MAPK pathway. Aside from regulation of proliferation, it is involved in mechanosensoric of cells. We investigated neurofibromin replacement in cultured human fibroblasts showing reduced amount of neurofibromin. Full length neurofibromin was produced recombinantly in insect cells and purified. Protein transduction into cultured fibroblasts was performed employing cell penetrating peptides along with photochemical internalization. This combination of transduction strategies ensures the intracellular uptake and the translocation to the cytoplasm of neurofibromin. The transduced neurofibromin is functional, indicated by functional rescue of reduced mechanosensoric blindness and reduced RasGAP activity in cultured fibroblasts of NF1 patients or normal fibroblasts treated by NF1 siRNA. Our study shows that recombinant neurofibromin is able to revert cellular effects of NF1 haploinsuffiency in vitro, indicating a use of protein transduction into cells as a potential treatment strategy for the monogenic disease NF1.

Mechanisms of Hydrocephalus after Neonatal and Adult Intraventricular Hemorrhage

PubMed Central

Strahle, Jennifer; Garton, Hugh J.L.; Maher, Cormac O.; Muraszko, Karin M.; Keep, Richard F.; Xi, Guohua

2013-01-01

Intraventricular hemorrhage (IVH) is a cause of significant morbidity and mortality and is an independent predictor of a worse outcome in intracerebral hemorrhage (ICH) and germinal matrix hemorrhage (GMH). IVH may result in both injuries to the brain as well as hydrocephalus. This paper reviews evidence on the mechanisms and potential treatments for IVH-induced hydrocephalus. One frequently cited theory to explain hydrocephalus after IVH involves obliteration of the arachnoid villi by microthrombi with subsequent inflammation and fibrosis causing CSF outflow obstruction. Although there is some evidence to support this theory, there may be other mechanisms involved, which contribute to the development of hydrocephalus. It is also unclear whether the causes of acute and chronic hydrocephalus after hemorrhage occur via different mechanisms; mechanical obstruction by blood in the former, and inflammation and fibrosis in the latter. Management of IVH and strategies for prevention of brain injury and hydrocephalus are areas requiring further study. A better understanding of the pathogenesis of hydrocephalus after IVH, may lead to improved strategies to prevent and treat post-hemorrhagic hydrocephalus. PMID:23976902

Loving-Kindness and Compassion Meditation: Potential for Psychological Interventions

PubMed Central

Hofmann, Stefan G.; Grossman, Paul; Hinton, Devon E.

2011-01-01

Mindfulness-based meditation interventions have become increasingly popular in contemporary psychology. Other closely related meditation practices include loving-kindness meditation (LKM) and compassion meditation (CM), exercises oriented toward enhancing unconditional, positive emotional states of kindness and compassion. This article provides a review of the background, the techniques, and the empirical contemporary literature of LKM and CM. The literature suggests that LKM and CM are associated with an increase in positive affect and a decrease in negative affect. Preliminary findings from neuroendocrine studies indicate that CM may reduce stress-induced subjective distress and immune response. Neuroimaging studies suggest that LKM and CM may enhance activation of brain areas that are involved in emotional processing and empathy. Finally, preliminary intervention studies support application of these strategies in clinical populations. It is concluded that, when combined with empirically supported treatments, such as cognitive behavioral therapy, LKM and CM may provide potentially useful strategies for targeting a variety of different psychological problems that involve interpersonal processes, such as social anxiety, marital conflict, anger, and coping with the strains of long-term caregiving. PMID:21840289

Short-Term Group Psychotherapy: A Clinical Trial of a New Combination of Pretreatment and Treatment Strategies.

ERIC Educational Resources Information Center

Merkel, William T.; Willis, Stephen L.

1985-01-01

The paper discusses a clinical trial of pretreatment and treatment strategies to enhance the effectiveness of short-term groups. Pretreatment strategies included preparing patients and increasing the perceived authority of the therapists. Treatment strategies include delineation of a specific treatment focus and a directive approach by the…

Internet-based interventions for disordered gamblers: study protocol for a randomized controlled trial of online self-directed cognitive-behavioural motivational therapy.

PubMed

Hodgins, David C; Fick, Gordon H; Murray, Robert; Cunningham, John A

2013-01-08

Gambling disorders affect about one percent of adults. Effective treatments are available but only a small proportion of affected individuals will choose to attend formal treatment. As a result, self-directed treatments have also been developed and found effective. Self-directed treatments provide individuals with information and support to initiate a recovery program without attending formal treatment. In previous research we developed an telephone-based intervention package that helps people to be motivated to tackle their gambling problem and to use basic behavioral and cognitive change strategies. The present study will investigate the efficacy of this self-directed intervention offered as a free online resource. The Internet is an excellent modality in which to offer self-directed treatment for gambling problems. The Internet is increasingly accessible to members of the public and is frequently used to access health-related information. Online gambling sites are also becoming more popular gambling platforms. A randomized clinical trial (N=180) will be conducted in which individuals with gambling problems who are not interested in attending formal treatment are randomly assigned to have access to an online self-directed intervention or to a comparison condition. The comparison condition will be an alternative website that offers a self-assessment of gambling involvement and gambling-related problems. The participant's use of the resources and their gambling involvement (days of gambling, dollars loss) and their gambling problems will be tracked for a twelve month follow-up period. The results of this research will be important for informing policy-makers who are developing treatment systems. ISRCTN06220098.

Correction to hill (2005).

PubMed

Hill, Clara E

2006-01-01

Reports an error in "Therapist Techniques, Client Involvement, and the Therapeutic Relationship: Inextricably Intertwined in the Therapy Process" by Clara E. Hill (Psychotherapy: Theory, Research, Practice, Training, 2005 Win, Vol 42(4), 431-442). An author's name was incorrectly spelled in a reference. The correct reference is presented. (The following abstract of the original article appeared in record 2006-03309-003.) I propose that therapist techniques, client involvement, and the therapeutic relationship are inextricably intertwined and need to be considered together in any discussion of the therapy process. Furthermore, I present a pantheoretical model of how these three variables evolve over four stages of successful therapy: initial impression formation, beginning the therapy (involves the components of facilitating client exploration and developing case conceptualization and treatment strategies), the core work of therapy (involves the components of theory-relevant tasks and overcoming obstacles), and termination. Theoretical propositions as well as implications for training and research are presented. (PsycINFO Database Record (c) 2010 APA, all rights reserved).

Optimization strategies for sediment reduction practices on roads in steep, forested terrain

USGS Publications Warehouse

Madej, Mary Ann; Eschenbach, E.A.; Diaz, C.; Teasley, R.; Baker, K.

2006-01-01

Many forested steeplands in the western United States display a legacy of disturbances due to timber harvest, mining or wildfires, for example. Such disturbances have caused accelerated hillslope erosion, leading to increased sedimentation in fish-bearing streams. Several restoration techniques have been implemented to address these problems in mountain catchments, many of which involve the removal of abandoned roads and re-establishing drainage networks across road prisms. With limited restoration funds to be applied across large catchments, land managers are faced with deciding which areas and problems should be treated first, and by which technique, in order to design the most effective and cost-effective sediment reduction strategy. Currently most restoration is conducted on a site-specific scale according to uniform treatment policies. To create catchment-scale policies for restoration, we developed two optimization models - dynamic programming and genetic algorithms - to determine the most cost-effective treatment level for roads and stream crossings in a pilot study basin with approximately 700 road segments and crossings. These models considered the trade-offs between the cost and effectiveness of different restoration strategies to minimize the predicted erosion from all forest roads within a catchment, while meeting a specified budget constraint. The optimal sediment reduction strategies developed by these models performed much better than two strategies of uniform erosion control which are commonly applied to road erosion problems by land managers, with sediment savings increased by an additional 48 to 80 per cent. These optimization models can be used to formulate the most cost-effective restoration policy for sediment reduction on a catchment scale. Thus, cost savings can be applied to further restoration work within the catchment. Nevertheless, the models are based on erosion rates measured on past restoration sites, and need to be up-dated as additional monitoring studies evaluate long-term basin response to erosion control treatments. Copyright ?? 2006 John Wiley & Sons, Ltd.

Ocular Involvement of Behçet's Syndrome: a Comprehensive Review.

PubMed

Ozyazgan, Yilmaz; Ucar, Didar; Hatemi, Gulen; Yazici, Yusuf

2015-12-01

Behçet's syndrome (BS) is a vasculitis involving several organ systems including the eyes. Ocular involvement is one of the most disabling complications of BS, causing loss of vision that may progress to blindness if left untreated. The typical form of ocular involvement is a relapsing and remitting panuveitis and retinal vasculitis. Initial attacks may spontaneously improve and subsequently disappear in a few weeks but tend to recur if left untreated. Destructive and recurrent attacks, especially with posterior segment and retina involvement, may cause irreversible ocular structural changes and permanent damage in sensory retina, resulting in loss of vision. The risk of irreversible damage to ocular tissue which may result in loss of vision warrants early and intensive treatment especially in patients at high risk such as young men who tend to follow an aggressive disease course. The management strategy involves rapid suppression of inflammation during the attacks and prevention of recurrent attacks. Local and systemic measures including immunosuppressives, corticosteroids, and biologic agents are used for this purpose. Surgery may be required in selected cases. The prognosis of eye involvement has greatly improved over the last decades with the effective use of immunosuppressives.

Oncogenic role of p21 in hepatocarcinogenesis suggests a new treatment strategy.

PubMed

Ohkoshi, Shogo; Yano, Masahiko; Matsuda, Yasunobu

2015-11-14

A well-known tumor suppressor, p21, acts paradoxically by promoting tumor growth in some cellular conditions. These conflicting functions have been demonstrated in association with the HBx gene and in hepatocarcinogenesis. The molecular behavior of p21 depends on its subcellular localization. Nuclear p21 may inhibit cell proliferation and be proapoptotic, while cytoplasmic p21 may have oncogenic and anti-apoptotic functions. Because most typical tumor suppressive proteins also have different effects according to subcellular localization, elucidating the regulatory mechanisms underlying nucleo-cytoplasmic transport of these proteins would be significant and may lead to a new strategy for anti-hepatocellular carcinoma (HCC) therapy. Chromosome region maintenance 1 (CRM1) is a major nuclear export receptor involved in transport of tumor suppressors from nucleus to cytoplasm. Expression of CRM1 is enhanced in a variety of malignancies and in vitro studies have shown the efficacy of specific inhibition of CRM1 against cancer cell lines. Interestingly, interferon may keep p21 in the nucleus; this is one of the mechanisms of its anti-hepatocarcinogenic function. Here we review the oncogenic property of p21, which depends on its subcellular localization, and discuss the rationale underlying a new strategy for HCC treatment and prevention.

Oncogenic role of p21 in hepatocarcinogenesis suggests a new treatment strategy

PubMed Central

Ohkoshi, Shogo; Yano, Masahiko; Matsuda, Yasunobu

2015-01-01

A well-known tumor suppressor, p21, acts paradoxically by promoting tumor growth in some cellular conditions. These conflicting functions have been demonstrated in association with the HBx gene and in hepatocarcinogenesis. The molecular behavior of p21 depends on its subcellular localization. Nuclear p21 may inhibit cell proliferation and be proapoptotic, while cytoplasmic p21 may have oncogenic and anti-apoptotic functions. Because most typical tumor suppressive proteins also have different effects according to subcellular localization, elucidating the regulatory mechanisms underlying nucleo-cytoplasmic transport of these proteins would be significant and may lead to a new strategy for anti-hepatocellular carcinoma (HCC) therapy. Chromosome region maintenance 1 (CRM1) is a major nuclear export receptor involved in transport of tumor suppressors from nucleus to cytoplasm. Expression of CRM1 is enhanced in a variety of malignancies and in vitro studies have shown the efficacy of specific inhibition of CRM1 against cancer cell lines. Interestingly, interferon may keep p21 in the nucleus; this is one of the mechanisms of its anti-hepatocarcinogenic function. Here we review the oncogenic property of p21, which depends on its subcellular localization, and discuss the rationale underlying a new strategy for HCC treatment and prevention. PMID:26576099

A challenge to the striking genotypic heterogeneity of retinitis pigmentosa: a better understanding of the pathophysiology using the newest genetic strategies

PubMed Central

Sorrentino, F S; Gallenga, C E; Bonifazzi, C; Perri, P

2016-01-01

Retinitis pigmentosa (RP) is a group of inherited retinal disorders characterized by a complex association between tremendous genotypic multiplicity and great phenotypic heterogeneity. The severity of the clinical manifestation depends on penetrance and expressivity of the disease-gene. Also, various interactions between gene expression and environmental factors have been hypothesized. More than 250 genes with ~4500 causative mutations have been reported to be involved in different RP-related mechanisms. Nowadays, not more than the 50% of RPs are attributable to identified genes, whereas the rest of molecular defects are still undetectable, especially in populations where few genetic screenings have been performed. Therefore, new genetic strategies can be a remarkably useful tool to aid clinical diagnosis, potentially modifying treatment options, and family counseling. Genome-wide analytical techniques (array comparative genomic hybridization and single-nucleotide polymorphism genotyping) and DNA sequencing strategies (arrayed primer extension, Sanger sequencing, and ultra high-throughput sequencing) are successfully used to early make molecular diagnosis detecting single or multiple mutations in the huge heterogeneity of RPs. To date, further research needs to be carried out to better investigate the genotype/phenotype correlation, putting together genetic and clinical findings to provide detailed information concerning the risk of RP development and novel effective treatments. PMID:27564722

Nanomedicine for Infectious Disease Applications: Innovation towards Broad-Spectrum Treatment of Viral Infections.

PubMed

Jackman, Joshua A; Lee, Jaywon; Cho, Nam-Joon

2016-03-02

Nanomedicine enables unique diagnostic and therapeutic capabilities to tackle problems in clinical medicine. As multifunctional agents with programmable properties, nanomedicines are poised to revolutionize treatment strategies. This promise is especially evident for infectious disease applications, for which the continual emergence, re-emergence, and evolution of pathogens has proven difficult to counter by conventional approaches. Herein, a conceptual framework is presented that envisions possible routes for the development of nanomedicines as superior broad-spectrum antiviral agents against enveloped viruses. With lipid membranes playing a critical role in the life cycle of medically important enveloped viruses including HIV, influenza, and Ebola, cellular and viral membrane interfaces are ideal elements to incorporate into broad-spectrum antiviral strategies. Examples are presented that demonstrate how nanomedicine strategies inspired by lipid membranes enable a wide range of targeting opportunities to gain control of critical stages in the virus life cycle through either direct or indirect approaches involving membrane interfaces. The capabilities can be realized by enabling new inhibitory functions or improving the function of existing drugs through nanotechnology-enabled solutions. With these exciting opportunities, due attention is also given to the clinical translation of nanomedicines for infectious disease applications, especially as pharmaceutical drug-discovery pipelines demand new routes of innovation. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Emerging strategies for cell and gene therapy of the muscular dystrophies

PubMed Central

Muir, Lindsey A.; Chamberlain, Jeffrey S.

2016-01-01

The muscular dystrophies are a heterogeneous group of over 40 disorders that are characterised by muscle weakness and wasting. The most common are Duchenne muscular dystrophy and Becker muscular dystrophy, which result from mutations within the gene encoding dystrophin; myotonic dystrophy type 1, which results from an expanded trinucleotide repeat in the myotonic dystrophy protein kinase gene; and facioscapulohumeral dystrophy, which is associated with contractions in the subtelomeric region of human chromosome 1. Currently the only treatments involve clinical management of symptoms, although several promising experimental strategies are emerging. These include gene therapy using adeno-associated viral, lentiviral and adenoviral vectors and nonviral vectors, such as plasmid DNA. Exon-skipping and cell-based therapies have also shown promise in the effective treatment and regeneration of dystrophic muscle. The availability of numerous animal models for Duchenne muscular dystrophy has enabled extensive testing of a wide range of therapeutic approaches for this type of disorder. Consequently, we focus here on the therapeutic developments for Duchenne muscular dystrophy as a model of the types of approaches being considered for various types of dystrophy. We discuss the advantages and limitations of each therapeutic strategy, as well as prospects and recent successes in the context of future clinical applications. PMID:19555515

Senile Dementia from Neuroscientific and Islamic Perspectives.

PubMed

Tumiran, Mohd Amzari; Abdul Rahman, Noor Naemah; Mohd Saat, Rohaida; Ismail, Ahmad Zuhdi; Ruzali, Wan Adriyani Wan; Bashar, Nurul Kabir Nurul; Hasan Adli, Durriyyah Sharifah

2018-02-01

Diseases involving the nervous system drastically change lives of victims and commonly increase dependency on others. This paper focuses on senile dementia from both the neuroscientific and Islamic perspectives, with special emphasis on the integration of ideas between the two different disciplines. This would enable effective implementation of strategies to address issues involving this disease across different cultures, especially among the world-wide Muslim communities. In addition, certain incongruence ideas on similar issues can be understood better. The former perspective is molded according to conventional modern science, while the latter on the analysis of various texts including the holy Qur'an, sunnah [sayings and actions of the Islamic prophet, Muhammad (pbuh)] and writings of Islamic scholars. Emphasis is particularly given on causes, symptoms, treatments and prevention of dementia.

Problem solving therapy - use and effectiveness in general practice.

PubMed

Pierce, David

2012-09-01

Problem solving therapy (PST) is one of the focused psychological strategies supported by Medicare for use by appropriately trained general practitioners. This article reviews the evidence base for PST and its use in the general practice setting. Problem solving therapy involves patients learning or reactivating problem solving skills. These skills can then be applied to specific life problems associated with psychological and somatic symptoms. Problem solving therapy is suitable for use in general practice for patients experiencing common mental health conditions and has been shown to be as effective in the treatment of depression as antidepressants. Problem solving therapy involves a series of sequential stages. The clinician assists the patient to develop new empowering skills, and then supports them to work through the stages of therapy to determine and implement the solution selected by the patient. Many experienced GPs will identify their own existing problem solving skills. Learning about PST may involve refining and focusing these skills.

Advancements in the Underlying Pathogenesis of Schizophrenia: Implications of DNA Methylation in Glial Cells.

PubMed

Chen, Xing-Shu; Huang, Nanxin; Michael, Namaka; Xiao, Lan

2015-01-01

Schizophrenia (SZ) is a chronic and severe mental illness for which currently there is no cure. At present, the exact molecular mechanism involved in the underlying pathogenesis of SZ is unknown. The disease is thought to be caused by a combination of genetic, biological, psychological, and environmental factors. Recent studies have shown that epigenetic regulation is involved in SZ pathology. Specifically, DNA methylation, one of the earliest found epigenetic modifications, has been extensively linked to modulation of neuronal function, leading to psychiatric disorders such as SZ. However, increasing evidence indicates that glial cells, especially dysfunctional oligodendrocytes undergo DNA methylation changes that contribute to the pathogenesis of SZ. This review primarily focuses on DNA methylation involved in glial dysfunctions in SZ. Clarifying this mechanism may lead to the development of new therapeutic interventional strategies for the treatment of SZ and other illnesses by correcting abnormal methylation in glial cells.

When love hurts. A systematic review on the effects of surgical and pharmacological treatments for endometriosis on female sexual functioning.

PubMed

Barbara, Giussy; Facchin, Federica; Meschia, Michele; Berlanda, Nicola; Frattaruolo, Maria P; VercellinI, Paolo

2017-06-01

Endometriosis is associated with an increased risk of dyspareunia, therefore this chronic gynecologic disease should be considered as a major cause of sexual dysfunctions. The aims of this study were to review the literature on the effects of surgical and pharmacological treatments for endometriosis on female sexual functioning, and to provide suggestions for future treatment strategies. We followed the PRISMA guidelines to conduct this systematic review, which involved an electronic database search of studies on the association between endometriosis and sexuality published between 2000 and 2016. As a result of the screening process, 22 studies were included in this systematic review. The 22 studies included were divided into two categories: (a) surgical intervention studies (n = 17), examining postoperative sexual outcomes of surgery for endometriosis; (b) pharmacological intervention studies (n = 5), evaluating the effects of pharmacological endometriosis treatments on sexual functioning. The studies considered showed that overall surgical and pharmacological interventions for endometriosis can lead to medium-/long-term improvement, but not necessarily to a definitive resolution of female sexual dysfunctions due to endometriosis. Sexual functioning is a multidimensional phenomenon and the ideal treatment for endometriosis-related sexual dysfunctions should be conducted by a multidisciplinary team that involves not only gynecologists, but also sexologists and psychologists/psychotherapists. Improving global sexual functioning, and not just reducing pain at intercourse, should be considered as a major clinical goal of endometriosis treatment. © 2016 Nordic Federation of Societies of Obstetrics and Gynecology.

Cancer treatment decision-making among young adults with lung and colorectal cancer: a comparison with adults in middle age.

PubMed

Mack, Jennifer W; Cronin, Angel; Fasciano, Karen; Block, Susan D; Keating, Nancy L

2016-09-01

Our aim is to understand experiences with treatment decision-making among young adults with cancer. We studied patients with lung cancer or colorectal cancer in the Cancer Care Outcomes Research and Surveillance Consortium, a prospective cohort study. We identified 148 young adult patients aged 21-40 years who completed baseline interview questions about cancer treatment decision-making; each was propensity score matched to three middle adult patients aged 41-60 years, for a cohort of 592 patients. Patients were asked about decision-making preferences, family involvement in decision-making, and worries about treatment. An ordinal logistic regression model evaluated factors associated with more treatment worries. Young and middle-aged adults reported similar decision-making preferences (p = 0.80) and roles relative to physicians (p = 0.36). Although family involvement was similar in the age groups (p = 0.21), young adults were more likely to have dependent children in the home (60% younger versus 28% middle-aged adults, p < 0.001). Young adults reported more worries about time away from family (p = 0.002), and, in unadjusted analyses, more cancer treatment-related worries (mean number of responses of 'somewhat' or 'very' worried 2.5 for younger versus 2.2 for middle-aged adults, p = 0.02.) However, in adjusted analyses, worries were associated with the presence of dependent children in the home (odds ratio [OR] 1.55, 95% CI = 1.07-2.24, p = 0.02), rather than age. Young adults involve doctors and family members in decisions at rates similar to middle-aged adults but experience more worries about time away from family. Patients with dependent children are especially likely to experience worries. Treatment decision-making strategies should be based on individual preferences and needs rather than age alone. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

Brazilian guidelines for the diagnosis and treatment of postmenopausal osteoporosis.

PubMed

Radominski, Sebastião Cézar; Bernardo, Wanderley; Paula, Ana Patrícia de; Albergaria, Ben-Hur; Moreira, Caio; Fernandes, Cesar Eduardo; Castro, Charlles H M; Zerbini, Cristiano Augusto de Freitas; Domiciano, Diogo S; Mendonça, Laura M C; Pompei, Luciano de Melo; Bezerra, Mailze Campos; Loures, Marco Antônio R; Wender, Maria Celeste Osório; Lazaretti-Castro, Marise; Pereira, Rosa M R; Maeda, Sergio Setsuo; Szejnfeld, Vera Lúcia; Borba, Victoria Z C

2017-01-01

Osteoporosis is the leading cause of fractures in the population older than 50 years. This silent disease affects primarily postmenopausal women and the elderly, and the morbidity and mortality rates are high. The main goal of treating osteoporosis is the prevention of fractures. The identification of populations at risk through early diagnosis and treatment is essential. The last Brazilian guideline for the treatment of postmenopausal osteoporosis was elaborated in 2002. Since then, new strategies for diagnosis and risk stratification have been developed, and drugs with novel action mechanisms have been added to the therapeutic arsenal. The Osteoporosis and Osteometabolic Diseases Committee of the Brazilian Society of Rheumatology, in conjunction with the Brazilian Medical Association and other Societies, has developed this update of the guidelines for the treatment of postmenopausal osteoporosis according to the best scientific evidence available. This update is intended for professionals in many medical and health specialties involved in the treatment of osteoporosis, for physicians in general and for health-related organizations. Copyright © 2017. Published by Elsevier Editora Ltda.

Therapeutic strategy with artificially-designed i-lncRNA targeting multiple oncogenic microRNAs exhibits effective antitumor activity in diffuse large B-cell lymphoma.

PubMed

Su, Yinghan; Sun, Bin; Lin, Xuejing; Zhao, Xinying; Ji, Weidan; He, Miaoxia; Qian, Haihua; Song, Xianmin; Yang, Jianmin; Wang, Jianmin; Chen, Jie

2016-08-02

In diffuse large B-cell lymphoma (DLBCL), many oncogenic microRNAs (OncomiRs) are highly expressed to promote disease development and progression by inhibiting the expression and function of certain tumor suppressor genes, and these OncomiRs comprise a promising new class of molecular targets for the treatment of DLBCL. However, most current therapeutic studies have focused on a single miRNA, with limited treatment outcomes. In this study, we generated tandem sequences of 10 copies of the complementary binding sequences to 13 OncomiRs and synthesized an interfering long non-coding RNA (i-lncRNA). The highly-expressed i-lncRNA in DLBCL cells would compete with the corresponding mRNAs of OncomiR target genes for binding OncomiRs, thereby effectively consuming a large amount of OncomiRs and protecting many tumor suppressor genes. The in vitro experiments confirmed that the i-lncRNA expression significantly inhibited cell proliferation, induced cell cycle arrest and apoptosis in DLBCL cell lines, mainly through upregulating the expression of PTEN, p27kip1, TIMP3, RECK and downregulating the expression of p38/MAPK, survivin, CDK4, c-myc. In the established SUDHL-4 xenografts in nude mice, the treatment strategy involving adenovirus-mediated i-lncRNA expression significantly inhibited the growth of DLBCL xenografts. Therefore, this treatment would specifically target the carcinogenic effects of many OncomiRs that are usually expressed in DLBCL and not in normal cells, such a strategy could improve anti-tumor efficacy and safety and may be a good prospect for clinical applications.

Leveraging Hypoxia-Activated Prodrugs to Prevent Drug Resistance in Solid Tumors.

PubMed

Lindsay, Danika; Garvey, Colleen M; Mumenthaler, Shannon M; Foo, Jasmine

2016-08-01

Experimental studies have shown that one key factor in driving the emergence of drug resistance in solid tumors is tumor hypoxia, which leads to the formation of localized environmental niches where drug-resistant cell populations can evolve and survive. Hypoxia-activated prodrugs (HAPs) are compounds designed to penetrate to hypoxic regions of a tumor and release cytotoxic or cytostatic agents; several of these HAPs are currently in clinical trial. However, preliminary results have not shown a survival benefit in several of these trials. We hypothesize that the efficacy of treatments involving these prodrugs depends heavily on identifying the correct treatment schedule, and that mathematical modeling can be used to help design potential therapeutic strategies combining HAPs with standard therapies to achieve long-term tumor control or eradication. We develop this framework in the specific context of EGFR-driven non-small cell lung cancer, which is commonly treated with the tyrosine kinase inhibitor erlotinib. We develop a stochastic mathematical model, parametrized using clinical and experimental data, to explore a spectrum of treatment regimens combining a HAP, evofosfamide, with erlotinib. We design combination toxicity constraint models and optimize treatment strategies over the space of tolerated schedules to identify specific combination schedules that lead to optimal tumor control. We find that (i) combining these therapies delays resistance longer than any monotherapy schedule with either evofosfamide or erlotinib alone, (ii) sequentially alternating single doses of each drug leads to minimal tumor burden and maximal reduction in probability of developing resistance, and (iii) strategies minimizing the length of time after an evofosfamide dose and before erlotinib confer further benefits in reduction of tumor burden. These results provide insights into how hypoxia-activated prodrugs may be used to enhance therapeutic effectiveness in the clinic.

CDK4/6 Inhibitors Sensitize Rb-positive Sarcoma Cells to Wee1 Kinase Inhibition through Reversible Cell-Cycle Arrest.

PubMed

Francis, Ashleigh M; Alexander, Angela; Liu, Yanna; Vijayaraghavan, Smruthi; Low, Kwang Hui; Yang, Dong; Bui, Tuyen; Somaiah, Neeta; Ravi, Vinod; Keyomarsi, Khandan; Hunt, Kelly K

2017-09-01

Research into the biology of soft tissue sarcomas has uncovered very few effective treatment strategies that improve upon the current standard of care which usually involves surgery, radiation, and chemotherapy. Many patients with large (>5 cm), high-grade sarcomas develop recurrence, and at that point have limited treatment options available. One challenge is the heterogeneity of genetic drivers of sarcomas, and many of these are not validated targets. Even when such genes are tractable targets, the rarity of each subtype of sarcoma makes advances in research slow. Here we describe the development of a synergistic combination treatment strategy that may be applicable in both soft tissue sarcomas as well as sarcomas of bone that takes advantage of targeting the cell cycle. We show that Rb-positive cell lines treated with the CDK4/6 inhibitor palbociclib reversibly arrest in the G 1 phase of the cell cycle, and upon drug removal cells progress through the cell cycle as expected within 6-24 hours. Using a long-term high-throughput assay that allows us to examine drugs in different sequences or concurrently, we found that palbociclib-induced cell-cycle arrest poises Rb-positive sarcoma cells (SK-LMS1 and HT-1080) to be more sensitive to agents that work preferentially in S-G 2 phase such as doxorubicin and Wee1 kinase inhibitors (AZD1775). The synergy between palbociclib and AZD1775 was also validated in vivo using SK-LMS1 xenografts as well as Rb-positive patient-derived xenografts (PDX) developed from leiomyosarcoma patients. This work provides the necessary preclinical data in support of a clinical trial utilizing this treatment strategy. Mol Cancer Ther; 16(9); 1751-64. ©2017 AACR . ©2017 American Association for Cancer Research.

Translating clinical science into effective therapies.

PubMed

Thase, Michael E

2014-05-01

Identifying a patient with treatment-resistant depression involves ensuring that at least 2 evidence-based antidepressant trials from two different pharmacologic classes have been undertaken and determining their impact on patients' symptoms, functioning, quality-of-life and social relationships as outcomes. When assessing depressive symptoms throughout the course of treatment, clinical judgment should be supplemented by using standardized tools such as the 9-item Patient Health Questionnaire (PHQ-9) and the Quick Inventory of Depressive Symptomatology (QIDS). Adjunctive treatment strategies preserve the benefits of first-line antidepressants in partial responders and potentially enhance the initial antidepressant's effect through complementary mechanisms of action. Novel "multimodal" pharmacotherapies with diverse potentially beneficial mechanisms of action are in development, which have varying degrees of activity across multiple monoamine systems including those regulated by serotonin, dopamine, and glutamate. © Copyright 2014 Physicians Postgraduate Press, Inc.

Diagnosis and Management of Systemic Sclerosis: A Practical Approach.

PubMed

Lee, Jason J; Pope, Janet E

2016-02-01

Systemic sclerosis is a devastating multisystem rheumatologic condition that is characterized by autoimmunity, tissue fibrosis, obliterative vasculopathy and inflammation. Clinical presentation and course of the condition vary greatly, which complicates both diagnosis and corresponding treatment. In this regard, recent advances in disease understanding, both clinically and biochemically, have led to newer classification criteria for systemic sclerosis that are more inclusive than ever before. Still, significant disease modifying therapies do not yet exist for most patients. Therefore, organ-based management strategies are employed and research has been directed within this paradigm focusing on either the most debilitating symptoms, such as Raynaud's phenomenon, digital ulcers and cutaneous sclerosis, or life-threatening organ involvement such as interstitial lung disease and pulmonary arterial hypertension. The current trends in systemic sclerosis diagnosis, evidence-based treatment recommendations and potential future directions in systemic sclerosis treatment are discussed.

Celecoxib and tauro-ursodeoxycholic acid co-treatment inhibits cell growth in familial adenomatous polyposis derived LT97 colon adenoma cells

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

Heumen, Bjorn W.H. van, E-mail: b.vanheumen@mdl.umcn.nl; Roelofs, Hennie M.J.; Morsche, Rene H.M. te

Chemoprevention would be a desirable strategy to avoid duodenectomy in patients with familial adenomatous polyposis (FAP) suffering from duodenal adenomatosis. We investigated the in vitro effects on cell proliferation, apoptosis, and COX-2 expression of the potential chemopreventives celecoxib and tauro-ursodeoxycholic acid (UDCA). HT-29 colon cancer cells and LT97 colorectal micro-adenoma cells derived from a patient with FAP, were exposed to low dose celecoxib and UDCA alone or in combination with tauro-cholic acid (CA) and tauro-chenodeoxycholic acid (CDCA), mimicking bile of FAP patients treated with UDCA. In HT-29 cells, co-treatment with low dose celecoxib and UDCA resulted in a decreased cellmore » growth (14-17%, p < 0.01). A more pronounced decrease (23-27%, p < 0.01) was observed in LT97 cells. Cell growth of HT-29 cells exposed to 'artificial bile' enriched with UDCA, was decreased (p < 0.001), either in the absence or presence of celecoxib. In LT97 cells incubated with 'artificial bile' enriched with UDCA, cell growth was decreased only in the presence of celecoxib (p < 0.05). No clear evidence was found for involvement of proliferating cell nuclear antigen, caspase-3, or COX-2 in the cellular processes leading to the observed changes in cell growth. In conclusion, co-treatment with low dose celecoxib and UDCA has growth inhibitory effects on colorectal adenoma cells derived from a patient with FAP, and further research on this combination as promising chemopreventive strategy is desired. -- Highlights: Black-Right-Pointing-Pointer Celecoxib and UDCA acid co-treatment decreases cell growth in colon tumor cells. Black-Right-Pointing-Pointer UDCA enriched 'artificial bile' decreases LT-97 cell growth only in presence of celecoxib. Black-Right-Pointing-Pointer PCNA, caspase-3, nor COX-2 seem to be involved in the observed changes in cell growth.« less

[Sequential prescriptions: Arguments for a change of therapeutic patterns in treatment resistant depressions].

PubMed

Allouche, G

2016-02-01

Among the therapeutic strategies in treatment of resistant depression, the use of sequential prescriptions is discussed here. A number of observations, initially quite isolated and few controlled studies, some large-scale, have been reported, which showed a definite therapeutic effect of certain requirements in sequential treatment of depression. The Sequenced Treatment Alternatives to Relieve Depression Study (STAR*D) is up to now the largest clinical trial exploring treatment strategies in non psychotic resistant depression in real-life conditions with an algorithm of sequential decision. The main conclusions of this study are the following: after two unsuccessful attempts, the chance of remission decreases considerably. A 12-months follow-up showed that the higher the use of the processing steps were high, the more common the relapses were during this period. The pharmacological differences between psychotropic did not cause clinically significant difference. The positive effect of lithium in combination with antidepressants has been known since the work of De Montigny. Antidepressants allow readjustment of physiological sequence involving different monoaminergic systems together. Studies with tricyclic antidepressant-thyroid hormone T3: in depression, decreased norepinephrine at the synaptic receptors believed to cause hypersensitivity of these receptors. Thyroid hormones modulate the activity of adrenergic receptors. There would be a balance of activity between alpha and beta-adrenergic receptors, depending on the bioavailability of thyroid hormones. ECT may in some cases promote pharmacological response in case of previous resistance, or be effective in preventing relapse. Cognitive therapy and antidepressant medications likely have an effect on different types of depression. We can consider the interest of cognitive therapy in a sequential pattern after effective treatment with an antidepressant effect for treatment of residual symptoms, preventing relapses and recurrences, in antidepressant maintenance. These data support the interest of therapeutic strategies based on evolutionary criteria. Sequential models inspired by statistical methods may incorporate the effects of a future treatment by measuring the current one. Copyright © 2015 L’Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.

Economic and Managerial Analysis of Effective Managerial Strategies on Prevention from Ketosis in Transition Period in Shahroud Commercial Dairy Farms

PubMed Central

Kashfi, H.; Yazdani, A. R.; Latifi, M.; Shirani Bidabadi, F.

2011-01-01

The purpose of this research is to study any effects of managerial strategies on prevention of ketosis metabolic disorder in transition period in Shahroud commercial dairy farms. For this purpose, a questionnaire was prepared in order to obtain required information about the performance of these managerial strategies, performance costs, involvement situation with disorders relying upon clinical signs and treatment and health records, producing and economic situation, and fertility rate and its costs. The considered managerial guidelines include body condition score management or type evaluation in transition period, increase in dry matter intake close to parturition, using propylene glycol, using niacin, and high-quality feeding (the importance of feed quality) in transition period. Finally and upon arrangement of data, it was possible to study any effects of mentioned managerial strategies on related variants through multiple linear regressions. Furthermore, in order to study any relation among variables, we considered Pearson correlation coefficients as well. Finally, it was revealed that any application of managerial strategies for prevention from Ketosis in transition period has a significant effect in betterment of managerial and economic parameters. PMID:23738102

A therapist-focused knowledge translation intervention for improving patient adherence in musculoskeletal physiotherapy practice.

PubMed

Babatunde, Folarin Omoniyi; MacDermid, Joy Christine; MacIntyre, Norma

2017-01-01

Nonadherence to treatment remains high among patients with musculoskeletal conditions with negative impact on the treatment outcomes, use of personal and cost of care. An active knowledge translation (KT) strategy may be an effective strategy to support practice change. The purpose of this study was to deliver a brief, interactive, multifaceted and targeted KT program to improve physiotherapist knowledge and confidence in performing adherence enhancing activities related to risk, barriers, assessment and interventions. We utilised a 2-phase approach in this KT project. Phase 1 involved the development of an adherence tool kit following a synthesis of the literature and an iterative process involving 47 end-users. Clinicians treating patients with musculoskeletal conditions were recruited from two Physiotherapy and Occupational therapy national conferences in Canada. The intervention, based on the acronym SIMPLE TIPS was tested on 51 physiotherapists in phase 2. A pre- and post-repeated measures design was used in Phase 2. Graham's knowledge-to-action cycle was used as the conceptual framework. Participants completed a pre-intervention assessment, took part in a 1-h educational session and completed a post-intervention assessment. A questionnaire was used to measure knowledge of evidence-based treatment adherence barriers, interventions and measures and confidence to perform evidence-based adherence practice activities. Data was analysed using descriptive statistics (frequency and percentage), Fisher's exact test and Wilcoxon Sign-Ranked tests. Barriers and facilitators of adherence were identified under three domains (therapist, patient, health system) in phase 1. Seventy percent of the participants completed the questionnaire. Results indicated that 46.8% of respondents explored barriers including the use of behaviour change strategies and 45.7% reported that they measured adherence but none reported the use of validated outcomes. A significant improvement in post-self-efficacy scores for the four adherence enhancing activities was observed immediately after the workshop. The use of a multi-modal KT intervention is feasible in an educational setting. A brief interactive educational session was successfully implemented using a toolkit and caused a significant increase in physiotherapists' knowledge and confidence at performing adherence enhancing activities in the very short-term. Further testing of SIMPLE TIPS on long-term adherence practices could help advance best practices specific to treatment adherence in MSK practice.

Current treatment for non-alcoholic fatty liver disease.

PubMed

Moctezuma-Velázquez, C

Non-alcoholic fatty liver disease is the most prevalent hepatopathy, estimated at 30% in the general population. In the coming years, it will likely be the most common indication for liver transplantation and the most frequent cause of hepatocellular carcinoma. Current treatment for non-alcoholic fatty liver disease is based on dietary and exercise interventions that have been shown to be efficacious, even for reverting fibrosis. Unfortunately, compliance with general measures involving lifestyle modifications is very poor, making pharmacologic strategies a necessary option. At present, there are no treatments for non-alcoholic fatty liver disease approved by regulatory agencies, and the only ones with sufficient evidence and recommended by international societies are treatments with pioglitazone and vitamin E, which are not exempt from adverse effects. We review herein the current management of non-alcoholic fatty liver disease, including dietary and physical activity interventions, available treatments, equivocal therapies, emerging treatments, and treatments presently in clinical trials. Copyright © 2018 Asociación Mexicana de Gastroenterología. Publicado por Masson Doyma México S.A. All rights reserved.

Coping with mental health issues: subjective experiences of self-help and helpful contextual factors at the start of mental health treatment

PubMed Central

Biringer, Eva; Davidson, Larry; Sundfør, Bengt; Lier, Haldis Ø.; Borg, Marit

2016-01-01

Abstract Background: Self-help strategies and various contextual factors support recovery. However, more in-depth knowledge is needed about how self-help strategies and supportive environments facilitate the recovery process. Aims: To explore what individuals who have recently been referred to a specialist Community Mental Health Center experience as helpful and what they do to help themselves. Method: Ten service users participated in in-depth interviews within a collaborative-reflexive framework. A hermeneutic-phenomenological approach was used. Results: Participants described a variety of helpful strategies and environmental supports. Four relevant main themes were identified: helpful activities, helpful people and places, self-instruction and learning about mental problems and medication and self-medication. Conclusions: The process of recovery is initiated before people become users of mental health services. This study confirms that recovery takes place within the person’s daily life context and involves the interplay of contextual factors, such as family, friends, good places, work and other meaningful activities. The coping strategies reported may represent an important focus for attention and clinical intervention. PMID:26484831

Recruiting seniors with chronic low back pain for a randomized controlled trial of a self-management program.

PubMed

Groupp, Elyse; Haas, Mitchell; Fairweather, Alisa; Ganger, Bonnie; Attwood, Michael

2005-02-01

To identify recruitment challenges and elucidate specific strategies that enabled recruitment of seniors for a randomized trial on low back pain comparing the Chronic Disease Self-management Program of the Stanford University to a 6-month wait-list control group. Recruitment for a randomized controlled trial. Community-based program offered at 12 locations. Community-dwelling seniors 60 years and older with chronic low back pain of mechanical origin. Passive recruitment strategies included advertisement in local and senior newspapers, in senior e-mail newsletters and listservs, in local community centers and businesses. Active strategies included meeting seniors at health fairs, lectures to the public and organizational meetings, and the help of trusted professionals in the community. A total of 100 white and 20 African American seniors were recruited. The program seemed to have the most appeal to white, middle-class older adults, educated through high school level. Advertisement failed to attract any participants to the program. Successful strategies included interaction with seniors at health fairs and lectures on health care, especially when the program was endorsed by a trusted community professional. Generating interest in the self-management program required keen communication skills because the idea of "self-management" was met with a myriad of responses, ranging from disinterest to disbelief. Generating interest also required active participation within the communities. Initial contacts had to be established with trusted professionals, whose endorsement enabled the project managers to present the concept of self-management to the seniors. More complex recruitment strategies were required for this study involving the self-management approach to back pain than for studies involving treatment.

Perspectives on counseling patients about menopausal hormone therapy: strategies in a complex data environment.

PubMed

Parish, Sharon J; Nappi, Rossella E; Kingsberg, Sheryl

2018-03-05

This narrative review strives to give healthcare providers (HCPs) who care for menopausal women better tools and skills to initiate discussions with women about menopause and hormone therapy (HT), communicate complex concepts and data, and promote shared decision-making. We review relevant studies on HT, barriers to treatment of menopausal symptoms, and effective communication strategies. We also provide recommendations for communicating with patients about HT based on the medical literature and our own professional experience. Both patient and HCP-related barriers can prevent women from accessing treatment for bothersome symptoms of menopause. Many women and HCPs have a poor understanding of the complex, nuanced data regarding HT. The benefits and risks vary with patient age and time since menopause, duration of use, inclusion of a progestin, and patient medical history. Women may also have fears about potential side effects of HT and feel unable to make informed choices. Strategies for effective patient communication and shared decision-making include use of open-ended questions to elicit patient's concerns and preferences, reflecting back to the patient what the HCP heard, presenting evidence about benefits and risks in language the patient can understand, keeping risks in perspective (eg, provide absolute, and also relative risks) without minimizing them, and making conscious efforts to minimize potential bias. Necessary components for achieving high-quality, shared decisions about HT involve a combination of medical evidence, communication skills, and recognition of patient goals and concerns. Use of such strategies can enhance women's satisfaction with care.

Human organ-on-a-chip BioMEMS devices for testing new diagnostic and therapeutic strategies

NASA Astrophysics Data System (ADS)

Leary, James F.; Key, Jaehong; Vidi, Pierre-Alexandre; Cooper, Christy L.; Kole, Ayeeshik; Reece, Lisa M.; Lelièvre, Sophie A.

2013-03-01

MEMS human "organs-on-a-chip" can be used to create model human organ systems for developing new diagnostic and therapeutic strategies. They represent a promising new strategy for rapid testing of new diagnostic and therapeutic approaches without the need for involving risks to human subjects. We are developing multicomponent, superparamagnetic and fluorescent nanoparticles as X-ray and MRI contrast agents for noninvasive multimodal imaging and for antibody- or peptide-targeted drug delivery to tumor and precancerous cells inside these artificial organ MEMS devices. Magnetic fields can be used to move the nanoparticles "upstream" to find their target cells in an organs-on-achip model of human ductal breast cancer. Theoretically, unbound nanoparticles can then be removed by reversing the magnetic field to give a greatly enhanced image of tumor cells within these artificial organ structures. Using branched PDMS microchannels and 3D tissue engineering of normal and malignant human breast cancer cells inside those MEMS channels, we can mimic the early stages of human ductal breast cancer with the goal to improve the sensitivity and resolution of mammography and MRI of very small tumors and test new strategies for treatments. Nanomedical systems can easily be imaged by multicolor confocal microscopy inside the artificial organs to test targeting and therapeutic responses including the differential viability of normal and tumor cells during treatments. Currently we are using 2-dimensional MEMS structures, but these studies can be extended to more complex 3D structures using new 3D printing technologies.

The impact of comorbid body dysmorphic disorder on the response to sequential pharmacological trials for obsessive-compulsive disorder.

PubMed

Diniz, Juliana B; Costa, Daniel Lc; Cassab, Raony Cc; Pereira, Carlos Ab; Miguel, Euripedes C; Shavitt, Roseli G

2014-06-01

Our aim was to investigate the impact of comorbid body dysmorphic disorder (BDD) on the response to sequential pharmacological trials in adult obsessive-compulsive disorder (OCD) patients. The sequential trial initially involved fluoxetine monotherapy followed by one of three randomized, add-on strategies: placebo, clomipramine or quetiapine. We included 138 patients in the initial phase of fluoxetine, up to 80 mg or the maximum tolerated dosage, for 12 weeks. We invited 70 non-responders to participate in the add-on trial; as 54 accepted, we allocated 18 to each treatment group and followed them for an additional 12 weeks. To evaluate the combined effects of sex, age, age at onset, initial severity, type of augmentation and BDD on the response to sequential treatments, we constructed a model using generalized estimating equations (GEE). Of the 39 patients who completed the study (OCD-BDD, n = 13; OCD-non-BDD, n = 26), the OCD-BDD patients were less likely to be classified as responders than the OCD-non-BDD patients (Pearson Chi-Square = 4.4; p = 0.036). In the GEE model, BDD was not significantly associated with a worse response to sequential treatments (z-robust = 1.77; p = 0.07). The predictive potential of BDD regarding sequential treatment strategies for OCD did not survive when the analyses were controlled for other clinical characteristics. © The Author(s) 2013.

Update on Clostridium difficile infections.

PubMed

Le Monnier, A; Zahar, J-R; Barbut, F

2014-08-01

Clostridium difficile infections (CDI) occur primarily in hospitalized patients with risk factors such as concomitant or recent use of antibiotics. CDI related additional costs are important for the global population and health-care facilities. CDI epidemiology has changed since 2003: they became more frequent boosted by large outbreaks, more severe, more resistant to antibiotic treatment, and spread to new groups of population without any risk factor. This is partly due to the emergence and worldwide dissemination of new and more virulent C. difficile strains such as the epidemic clone 027/NAP1/BI. The host immune response plays a central role in the pathogenesis of CDI and could also be involved in the occurrence of recurrent or severe forms. New guidelines including new molecular tests (NAAT) have recently clarified and simplified the diagnostic strategies for the microbiological diagnosis of CDI. The CDI incidence was proven to be related to the level of clinical suspicion and the frequency of microbiological screening for C. difficile. The current recommendations for the treatment of CDI mention oral metronidazole as the first line treatment for mild to moderate diarrhea. Oral vancomycin use should be restricted to severe cases. In the absence of consensus, the treatment of multiple recurrences remains a major concern. New and more targeted antibiotics and innovative therapeutic strategies (fecal transplantation, monoclonal antibodies, and vaccination) have emerged as new therapies for CDI. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Optimization of remotely delivered intensive lifestyle treatment for obesity using the Multiphase Optimization Strategy: Opt-IN study protocol.

PubMed

Pellegrini, Christine A; Hoffman, Sara A; Collins, Linda M; Spring, Bonnie

2014-07-01

Obesity-attributable medical expenditures remain high, and interventions that are both effective and cost-effective have not been adequately developed. The Opt-IN study is a theory-guided trial using the Multiphase Optimization Strategy (MOST) to develop an optimized, scalable version of a technology-supported weight loss intervention. Opt-IN aims to identify which of 5 treatment components or component levels contribute most meaningfully and cost-efficiently to the improvement of weight loss over a 6 month period. Five hundred and sixty obese adults (BMI 30-40 kg/m(2)) between 18 and 60 years old will be randomized to one of 16 conditions in a fractional factorial design involving five intervention components: treatment intensity (12 vs. 24 coaching calls), reports sent to primary care physician (No vs. Yes), text messaging (No vs. Yes), meal replacement recommendations (No vs. Yes), and training of a participant's self-selected support buddy (No vs. Yes). During the 6-month intervention, participants will monitor weight, diet, and physical activity on the Opt-IN smartphone application downloaded to their personal phone. Weight will be assessed at baseline, 3, and 6 months. The Opt-IN trial is the first study to use the MOST framework to develop a weight loss treatment that will be optimized to yield the best weight loss outcome attainable for $500 or less. Copyright © 2014 Elsevier Inc. All rights reserved.

Acetyl-L-carnitine and oxaloacetate in post-treatment against LTP impairment in a rat ischemia model. An in vitro electrophysiological study.

PubMed

Kocsis, K; Knapp, L; Mészáros, J; Kis, Z; Farkas, T; Vécsei, L; Toldi, J

2015-06-01

A high proportion of research relating to cerebral ischemia focuses on neuroprotection. The application of compounds normally present in the organism is popular, because they do not greatly influence the synaptic activity by receptor modulation, and can be administered without serious side effects. Oxaloacetate (OxAc) and acetyl-L-carnitine (ALC) are such favorable endogenous molecules. ALC can exert a protective effect by improving the energy state of the neurons under ischemic conditions. A promising neuroprotective strategy is glutamate scavenging, which can be achieved by the intravenous administration of OxAc. This study involved the possible protective effects of ALC and OxAc in different post-treatment protocols against long-term potentiation (LTP) impairment. Ischemia was induced in rats by 2-vessel occlusion, which led to a decreased LTP relative to the control group. High-dose (200 mg/kg) ALC or OxAc post-treatment resulted in a higher potentiation relative to the 2VO group, but it did not reach the control level, whereas low-dose ALC (100 mg/kg) in combination with OxAc completely restored the LTP function. Many previous studies have concluded that ALC can be protective only as pretreatment. The strategy described here reveals that ALC can also be neuroprotective when utilized as post-treatment against ischemia.

A Tale of Two Temporal Coding Strategies: Common and Dissociable Brain Regions Involved in Recency versus Associative Temporal Order Retrieval Strategies.

PubMed

Lieberman, Jennifer S; Kyle, Colin T; Schedlbauer, Amber; Stokes, Jared; Ekstrom, Arne D

2017-04-01

Numerous studies indicate the importance of the hippocampus to temporal order retrieval. However, behavioral studies suggest that there are different ways to retrieve temporal order information from encoded sequences, one involving an associative strategy (retrieving associations using neighboring items in a list) and another involving a recency strategy (determining which of two items came first). It remains unresolved, however, whether both strategies recruit the hippocampus or only associative strategies, consistent with the hippocampus's role in relational processing. To address this, we developed a paradigm in which we dissociated associative versus recency-based retrieval, involving the same stimulus presentation during retrieval. Associative retrieval involved an increase in RT (and decrease in performance) with greater distances between intervals, consistent with the need to retrieve intervening associations. Recency-based retrieval involved an increase in RT (and decrease in performance) with shorter distances between intervals, suggesting the use of a strength-based coding mechanism to retrieve information. We employed fMRI to determine the neural basis of the different strategies. Both strategies showed significant levels of hippocampal activation and connectivity that did not differ between tasks. In contrast, both univariate and connectivity pattern analyses revealed differences in extrahippocampal areas such as parietal and frontal cortices. A covariate analysis suggested that differences could not be explained by task difficulty alone. Together, these findings suggest that the hippocampus plays a role in both forms of temporal order retrieval, with neocortical networks mediating the different cognitive demands for associative versus recency-based temporal order retrieval.

Pulmonary vein stenosis following catheter ablation of atrial fibrillation.

PubMed

Pürerfellner, Helmut; Martinek, Martin

2005-11-01

This review provides an update on the mechanisms, incidence, and current management of significant pulmonary vein stenosis following catheter ablation of atrial fibrillation. Catheter ablation involving the pulmonary veins and the surrounding left atrial tissue is increasingly used to treat atrial fibrillation. In parallel with the fact that these procedures may cure a substantial proportion of patients, severe complications have been observed. Pulmonary vein stenosis is a new clinical entity produced by radiofrequency energy delivery mainly within or at the orifice of the pulmonary veins. The exact incidence is currently unknown because the diagnosis is dependent on the imaging modality and on the rigor with which patients are followed up. The optimal method for screening patients has not been determined. Stenosis of a pulmonary vein may be assessed by combining anatomic and functional imaging using computed tomographic or magnetic resonance imaging, transesophageal echocardiography, and lung scanning. Symptoms vary considerably and may be misdiagnosed, leading to severe clinical consequences. Current treatment strategies involve pulmonary vein dilatation or stenting; however, the restenosis rate remains high. The long-term outcome in patients with pulmonary vein stenosis is unclear. Strategies under development to prevent pulmonary vein stenosis include alternate energy sources and modified ablation techniques. Pulmonary vein stenosis following catheter ablation is a new clinical entity that has been described in various reports recently. There is much uncertainty with respect to causative factors, incidence, diagnosis, and treatment, and long-term sequelae are unclear.

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

Saelices, Lorena; Johnson, Lisa M.; Liang, Wilson Y.

The tetrameric thyroxine transport protein transthyretin (TTR) forms amyloid fibrils upon dissociation and monomer unfolding. The aggregation of transthyretin has been reported as the cause of the life-threatening transthyretin amyloidosis. The standard treatment of familial cases of TTR amyloidosis has been liver transplantation. Although aggregation-preventing strategies involving ligands are known, understanding the mechanism of TTR aggregation can lead to additional inhibition approaches. Several models of TTR amyloid fibrils have been proposed, but the segments that drive aggregation of the protein have remained unknown. Here we identify β-strands F and H as necessary for TTR aggregation. Based on the crystal structuresmore » of these segments, we designed two non-natural peptide inhibitors that block aggregation. Lastly, this work provides the first characterization of peptide inhibitors for TTR aggregation, establishing a novel therapeutic strategy.« less

Laboratory equipment maintenance: a critical bottleneck for strengthening health systems in sub-Saharan Africa?

PubMed

Fonjungo, Peter N; Kebede, Yenew; Messele, Tsehaynesh; Ayana, Gonfa; Tibesso, Gudeta; Abebe, Almaz; Nkengasong, John N; Kenyon, Thomas

2012-02-01

Properly functioning laboratory equipment is a critical component for strengthening health systems in developing countries. The laboratory can be an entry point to improve population health and care of individuals for targeted diseases - prevention, care, and treatment of TB, HIV/AIDS, and malaria, plus maternal and neonatal health - as well as those lacking specific attention and funding. We review the benefits and persistent challenges associated with sustaining laboratory equipment maintenance. We propose equipment management policies as well as a comprehensive equipment maintenance strategy that would involve equipment manufacturers and strengthen local capacity through pre-service training of biomedical engineers. Strong country leadership and commitment are needed to assure development and sustained implementation of policies and strategies for standardization of equipment, and regulation of its procurement, donation, disposal, and replacement.

Signals from the Fourth Dimension Regulate Drug Relapse.

PubMed

Mulholland, Patrick J; Chandler, L Judson; Kalivas, Peter W

2016-07-01

Despite the enormous societal burden of alcohol and drug addiction and abundant research describing drug-induced maladaptive synaptic plasticity, there are few effective strategies for treating substance use disorders. Recent awareness that synaptic plasticity involves astroglia and the extracellular matrix is revealing new possibilities for understanding and treating addiction. We first review constitutive corticostriatal adaptations that are elicited by and shared between all abused drugs from the perspective of tetrapartite synapses, and integrate recent discoveries regarding cell type-specificity in striatal neurons. Next, we describe recent discoveries that drug-seeking is associated with transient synaptic plasticity that requires all four synaptic elements and is shared across drug classes. Finally, we prognosticate how considering tetrapartite synapses can provide new treatment strategies for addiction. Copyright © 2016 Elsevier Ltd. All rights reserved.

In defense of genuine ignorance: supporting vitality and relevance in graduate curricula.

PubMed

Goren, S; Peter, L; Fischer, S

1992-01-01

Genuine ignorance, defined by John Dewey as curiosity and openmindedness in opposition to repetition of catch phrases and familiar propositions, is nurtured in graduate nursing curricula in which the educational process is congruent with course content. Preparation for advanced practice in the mental health environment of the foreseeable future required abandonment of the familiar medical model in favor of conceptual models consistent with current thinking in psychiatric nursing and exposure to current problems (homelessness, family violence, AIDS) and current problem solving strategies (brief treatment, family preservation). Involvement in practice-based research and operationalizing new perspectives on familiar clinical problems, are suggested as strategies for developing the advanced practitioner. Two of the authors, former graduate students, describe the impact of changed perspectives and research activity on their own practice.

Biomaterial based cardiac tissue engineering and its applications

PubMed Central

Huyer, Locke Davenport; Montgomery, Miles; Zhao, Yimu; Xiao, Yun; Conant, Genevieve; Korolj, Anastasia; Radisic, Milica

2015-01-01

Cardiovascular disease is a leading cause of death worldwide, necessitating the development of effective treatment strategies. A myocardial infarction involves the blockage of a coronary artery leading to depletion of nutrient and oxygen supply to cardiomyocytes and massive cell death in a region of the myocardium. Cardiac tissue engineering is the growth of functional cardiac tissue in vitro on biomaterial scaffolds for regenerative medicine application. This strategy relies on the optimization of the complex relationship between cell networks and biomaterial properties. In this review, we discuss important biomaterial properties for cardiac tissue engineering applications, such as elasticity, degradation, and induced host response, and their relationship to engineered cardiac cell environments. With these properties in mind, we also emphasize in vitro use of cardiac tissues for high-throughput drug screening and disease modelling. PMID:25989939

International non-governmental organizations' provision of community-based tuberculosis care for hard-to-reach populations in Myanmar, 2013-2014.

PubMed

Soe, Kyaw Thu; Saw, Saw; van Griensven, Johan; Zhou, Shuisen; Win, Le; Chinnakali, Palanivel; Shah, Safieh; Mon, Myo Myo; Aung, Si Thu

2017-03-24

National tuberculosis (TB) programs increasingly engage with international non-governmental organizations (INGOs), especially to provide TB care in complex settings where community involvement might be required. In Myanmar, however, there is limited data on how such INGO community-based programs are organized and how effective they are. In this study, we describe four INGO strategies for providing community-based TB care to hard-to-reach populations in Myanmar, and assess their contribution to TB case detection. We conducted a descriptive study using program data from four INGOs and the National TB Program (NTP) in 2013-2014. For each INGO, we extracted information on its approach and key activities, the number of presumptive TB cases referred and undergoing TB testing, and the number of patients diagnosed with TB and their treatment outcomes. The contribution of INGOs to TB diagnosis in their selected townships was calculated as the proportion of INGO-diagnosed new TB cases out of the total NTP-diagnosed new TB cases in the same townships. All four INGOs implemented community-based TB care in challenging contexts, targeting migrants, post-conflict areas, the urban poor, and other vulnerable populations. Two recruited community volunteers via existing community health volunteers or health structures, one via existing community leaderships, and one directly involved TB infected/affected individuals. Two INGOs compensated volunteers via performance-based financing, and two provided financial and in-kind initiatives. All relied on NTP laboratories for diagnosis and TB drugs, but provided direct observation treatment support and treatment follow-up. A total of 21 995 presumptive TB cases were referred for TB diagnosis, with 7 383 (34%) new TB cases diagnosed and almost all (98%) successfully treated. The four INGOs contributed to the detection of, on average, 36% (7 383/20 663) of the total new TB cases in their respective townships (range: 15-52%). Community-based TB care supported by INGOs successfully achieved TB case detection in hard-to-reach and vulnerable populations. This is vital to achieving the World Health Organization End TB Strategy targets. Strategies to ensure sustainability of the programs should be explored, including the need for longer-term commitment of INGOs.

Effectiveness of secondary prevention and treatment interventions for crack-cocaine abuse: a comprehensive narrative overview of English-language studies.

PubMed

Fischer, Benedikt; Blanken, Peter; Da Silveira, Dartiu; Gallassi, Andrea; Goldner, Elliot M; Rehm, Jürgen; Tyndall, Mark; Wood, Evan

2015-04-01

There are an estimated several million crack-cocaine users globally; use is highest in the Americas. Most crack users are socio-economically marginalized (e.g., homeless), and feature elevated risks for morbidity (e.g., blood-borne viruses), mortality and crime/violence involvement, resulting in extensive burdens. No comprehensive reviews of evidence-based prevention and/or treatment interventions specifically for crack use exist. We conducted a comprehensive narrative overview of English-language studies on the efficacy of secondary prevention and treatment interventions for crack (cocaine) abuse/dependence. Literature searches (1990-2014) using pertinent keywords were conducted in main scientific databases. Titles/abstracts were reviewed for relevance, and full studies were included in the review if involving a primary prevention/treatment intervention study comprising a substantive crack user sample. Intervention outcomes considered included drug use, health risks/status (e.g., HIV or sexual risks) and select social outcome indicators. Targeted (e.g., behavioral/community-based) prevention measures show mixed and short-term effects on crack use/HIV risk outcomes. Material (e.g., safer crack use kit distribution) interventions also document modest efficacy in risk reduction; empirical assessments of environmental (e.g., drug consumption facilities) for crack smokers are not available. Diverse psycho-social treatment (including contingency management) interventions for crack abuse/dependence show some positive but also limited/short-term efficacy, yet likely constitute best currently available treatment options. Ancillary treatments show little effects but are understudied. Despite ample studies, pharmaco-therapeutic/immunotherapy treatment agents have not produced convincing evidence; select agents may hold potential combined with personalized approaches and/or psycho-social strategies. No comprehensively effective 'gold-standard' prevention/treatment interventions for crack abuse exist; concerted research towards improved interventions is urgently needed. Copyright © 2015 Elsevier B.V. All rights reserved.

Medicaid Coverage of Methadone Maintenance and the Use of Opioid Agonist Therapy Among Pregnant Women in Specialty Treatment.

PubMed

Bachhuber, Marcus A; Mehta, Pooja K; Faherty, Laura J; Saloner, Brendan

2017-12-01

Opioid agonist therapy (OAT) is the standard of care for pregnant women with opioid use disorder (OUD). Medicaid coverage policies may strongly influence OAT use in this group. To examine the association between Medicaid coverage of methadone maintenance and planned use of OAT in the publicly funded treatment system. Retrospective cross-sectional analysis of treatment admissions in 30 states extracted from the Treatment Episode Data Set (2013 and 2014). Medicaid-insured pregnant women with OUD (n=3354 treatment admissions). The main outcome measure was planned use of OAT on admission. The main exposure was state Medicaid coverage of methadone maintenance. Using multivariable logistic regression models adjusting for sociodemographic, substance use, and treatment characteristics, we compared the probability of planned OAT use in states with Medicaid coverage of methadone maintenance versus states without coverage. A total of 71% of pregnant women admitted to OUD treatment were 18-29 years old, 85% were white non-Hispanic, and 56% used heroin. Overall, 74% of admissions occurred in the 18 states with Medicaid coverage of methadone maintenance and 53% of admissions involved planned use of OAT. Compared with states without Medicaid coverage of methadone maintenance, admissions in states with coverage were significantly more likely to involve planned OAT use (adjusted difference: 32.9 percentage points, 95% confidence interval, 19.2-46.7). Including methadone maintenance in the Medicaid benefit is essential to increasing OAT among pregnant women with OUD and should be considered a key policy strategy to enhance outcomes for mothers and newborns.

Clinician Approaches and Strategies for Engaging Older Men in Depression Care

PubMed Central

Apesoa-Varano, Ester Carolina; Hinton, Ladson; Barker, Judith C.; Unützer, Jürgen

2010-01-01

OBJECTIVE The aim of this study is to explore primary care physicians’ (PCPs) and depression care managers’ (DCMs) approaches to diagnosing and treating depression in older men. The authors focus on older men because studies have shown that they are under-treated compared with women and younger groups. The authors contribute to previous research by identifying facilitators of care for older men from the perspective of clinicians. METHODS Participants in this study were part of the Improving Mood-Promoting access to Collaborative Treatment (IMPACT) trial, an effectiveness study of collaborative care for late-life depression in 18 diverse primary care practices. Nine PCPs and 11 DCMs were interviewed to collect information on specific roles in caring for depressed patients and their experiences in working with depressed older men. All interviews were tape-recorded, transcribed verbatim and analyzed thematically in several steps using standard qualitative data analysis techniques. RESULTS The authors identified three general approaches to building trust and talking about the depression: 1) an indirect approach (“call it something else”), 2) a gradual approach (“building up to depression”), and 3) a direct approach (“shock and awe”). The authors also found specific strategies that PCPs and DCMs used to manage depression among elderly male patients, such as increased monitoring of mood, treating somatic symptoms first, medicalizing depression, and enlisting the cooperation of family. In our interviews, enlisting family involvement was the most prominent strategy used by clinicians. CONCLUSIONS A variety of approaches and strategies are used by clinicians for diagnosing and treating depressed older men. Clinicians change strategies as a response to a patient's compliance with treatment and the decision about which strategy to pursue is usually made on an “on-the-go” basis throughout the course of clinician-patient interaction. Based on clinicians’ experience, depression management requires concerted efforts and persistence, and the family seems to play an important role in how older men receive the diagnosis of depression and adhere to clinicians’ prescribed treatment. However, more research is needed to discover the best way of engaging and working with family members to facilitate effective depression care for older adults. PMID:20220598

Combining Cytotoxic and Immune-Mediated Gene Therapy to Treat Brain Tumors

PubMed Central

Curtin, James F.; King, Gwendalyn D.; Candolfi, Marianela; Greeno, Remy B.; Kroeger, Kurt M.; Lowenstein, Pedro R.; Castro, Maria G.

2006-01-01

Glioblastoma (GBM) is a type of intracranial brain tumor, for which there is no cure. In spite of advances in surgery, chemotherapy and radiotherapy, patients die within a year of diagnosis. Therefore, there is a critical need to develop novel therapeutic approaches for this disease. Gene therapy, which is the use of genes or other nucleic acids as drugs, is a powerful new treatment strategy which can be developed to treat GBM. Several treatment modalities are amenable for gene therapy implementation, e.g. conditional cytotoxic approaches, targeted delivery of toxins into the tumor mass, immune stimulatory strategies, and these will all be the focus of this review. Both conditional cytotoxicity and targeted toxin mediated tumor death, are aimed at eliminating an established tumor mass and preventing further growth. Tumors employ several defensive strategies that suppress and inhibit anti-tumor immune responses. A better understanding of the mechanisms involved in eliciting anti-tumor immune responses has identified promising targets for immunotherapy. Immunotherapy is designed to aid the immune system to recognize and destroy tumor cells in order to eliminate the tumor burden. Also, immune-therapeutic strategies have the added advantage that an activated immune system has the capability of recognizing tumor cells at distant sites from the primary tumor, therefore targeting metastasis distant from the primary tumor locale. Pre-clinical models and clinical trials have demonstrated that in spite of their location within the central nervous system (CNS), a tissue described as ‘immune privileged’, brain tumors can be effectively targeted by the activated immune system following various immunotherapeutic strategies. This review will highlight recent advances in brain tumor immunotherapy, with particular emphasis on advances made using gene therapy strategies, as well as reviewing other novel therapies that can be used in combination with immunotherapy. Another important aspect of implementing gene therapy in the clinical arena is to be able to image the targeting of the therapeutics to the tumors, treatment effectiveness and progression of disease. We have therefore reviewed the most exciting non-invasive, in vivo imaging techniques which can be used in combination with gene therapy to monitor therapeutic efficacy over time. PMID:16248789

[Strategies of treatment for febrile neutropenia].

PubMed

Terui, Yasuhito

2013-06-01

The guideline on febrile neutropenia(FN)was published by the Japanese Society of Medical Oncology(JSMO)in 2012. Based on this guideline, the treatment strategy for febrile neutropenia that is discussed in this paper includes empiric treatment strategies, methicillin-resistant Staphylococcus aureus antibiotics in the initial treatment, treatment for severe FN, treatment for outpatients, duration of FN treatment, treatment after recovery from fever associated with neutropenia, and empiric treatment with anti-fungal drugs in patients with prolonged FN.

Application of Chemical Genomics to Plant-Bacteria Communication: A High-Throughput System to Identify Novel Molecules Modulating the Induction of Bacterial Virulence Genes by Plant Signals.

PubMed

Vandelle, Elodie; Puttilli, Maria Rita; Chini, Andrea; Devescovi, Giulia; Venturi, Vittorio; Polverari, Annalisa

2017-01-01

The life cycle of bacterial phytopathogens consists of a benign epiphytic phase, during which the bacteria grow in the soil or on the plant surface, and a virulent endophytic phase involving the penetration of host defenses and the colonization of plant tissues. Innovative strategies are urgently required to integrate copper treatments that control the epiphytic phase with complementary tools that control the virulent endophytic phase, thus reducing the quantity of chemicals applied to economically and ecologically acceptable levels. Such strategies include targeted treatments that weaken bacterial pathogens, particularly those inhibiting early infection steps rather than tackling established infections. This chapter describes a reporter gene-based chemical genomic high-throughput screen for the induction of bacterial virulence by plant molecules. Specifically, we describe a chemical genomic screening method to identify agonist and antagonist molecules for the induction of targeted bacterial virulence genes by plant extracts, focusing on the experimental controls required to avoid false positives and thus ensuring the results are reliable and reproducible.

Application of bee venom and its main constituent melittin for cancer treatment.

PubMed

Liu, Cui-Cui; Hao, Ding-Jun; Zhang, Qian; An, Jing; Zhao, Jing-Jing; Chen, Bo; Zhang, Ling-Ling; Yang, Hao

2016-12-01

Bee venom and its main constituent melittin (MEL) have been extensively studied in the treatment of tumors. However, the non-specific cytotoxicity and hemolytic activity have hampered the clinical application. Currently, a number of research groups have reported a series of optimization strategies, including gene therapy, recombinant immunotoxin incorporating MEL or MEL nanoparticles, targeting tumor cells to attenuate the cytotoxicity and improve its antitumor efficiency and therapeutic capabilities, which have shown very promising in overcoming some of these obstacles. In this review, we summarize the current knowledge regarding anticancer effects of bee venom and its main compound MEL on different kinds of tumor cells as well as elucidate their possible anticancer mechanisms. It could be concluded that MEL exerts multiple effects on cellular functions of cancerous cells such as proliferation, apoptosis, metastasis, angiogenesis as well as cell cycle, and the anticancer processes involve diverse signal molecules and regulatory pathways. We also highlight the recent research progress for efficient delivery of MEL peptide, thus providing new ideas and hopeful strategies for the in vivo application of MEL.

Depression in young people. A growing challenge for primary care.

PubMed

Cosgrave, E; McGorry, P; Allen, N; Jackson, H

2000-02-01

Recent research indicates that 27% of young people aged 18-24 have a mental health problem involving mood, anxiety, personality and/or substance abuse disorders and 15-40% report depressive symptomatology. A proportion of these young people will suicide. The morbidity associated with depressive illness in this age group is high, with those experiencing a depressive episode having reduced vocational and life prospects and being highly vulnerable to further episodes in later life. To outline the clinical features of depression in young people and to provide strategies for appropriate management. Presentation of depression in young people is likely to vary from accepted diagnostic criteria with non specific symptoms such as boredom, anxiety, failing adjustment and sleep disturbance predominating. Management includes attending to key social problems, ensuring a safe environment and counselling, which may be supportive counselling or more specific treatments of cognitive behavioural therapy or interpersonal psychotherapy. Medication is indicated for more severe depression or with failure of response to psychological strategies. Early case identification and intensive treatment of first episodes of depression is important in reducing prevalence, cost and morbidity.

Mechanisms of Resistance to Endocrine Therapy in Breast Cancer: Focus on Signaling Pathways, miRNAs and Genetically Based Resistance

PubMed Central

García-Becerra, Rocío; Santos, Nancy; Díaz, Lorenza; Camacho, Javier

2013-01-01

Breast cancer is the most frequent malignancy diagnosed in women. Approximately 70% of breast tumors express the estrogen receptor (ER). Tamoxifen and aromatase inhibitors (AIs) are the most common and effective therapies for patients with ERα-positive breast cancer. Alone or combined with chemotherapy, tamoxifen significantly reduces disease progression and is associated with more favorable impact on survival in patients. Unfortunately, endocrine resistance occurs, either de novo or acquired during the course of the treatment. The mechanisms that contribute to hormonal resistance include loss or modification in the ERα expression, regulation of signal transduction pathways, altered expression of specific microRNAs, balance of co-regulatory proteins, and genetic polymorphisms involved in tamoxifen metabolic activity. Because of the clinical consequences of endocrine resistance, new treatment strategies are arising to make the cells sensitive to tamoxifen. Here, we will review the current knowledge on mechanisms of endocrine resistance in breast cancer cells. In addition, we will discuss novel therapeutic strategies to overcome such resistance. Undoubtedly, circumventing endocrine resistance should help to improve therapy for the benefit of breast cancer patients. PMID:23344024

Adoptive cell therapy of prostate cancer using female mice-derived T cells that react with prostate antigens

PubMed Central

Yi, Huanfa; Yu, Xiaofei; Guo, Chunqing; Manjili, Masoud H.; Repasky, Elizabeth A.; Wang, Xiang-Yang

2011-01-01

In this study, we report a novel treatment strategy that could potentially be used to improve efficacy of adoptive cell therapy for patients with prostate cancer. We show that female C57BL/6 mice are able to effectively reject two syngeneic prostate tumors (TRAMP-C2 and RM1) in a T cell-dependent manner. The protective antitumor immunity appears to primarily involve T cell responses reactive against general prostate tumor/tissue antigens, rather than simply to male-specific H-Y antigen. For the first time we show that adoptive transfer of lymphocytes from TRAMP-C2-primed or naive female mice effectively control prostate tumor growth in male mice, when combined with host pre-conditioning (i.e., non-myeloablative lymphodepletion) and IL-2 administration. No pathological autoimmune response was observed in the treated tumor-bearing male mice. Our studies provide new insights regarding the immune-mediated recognition of male-specific tissue, such as the prostate, and may offer new immunotherapy treatment strategies for advanced prostate cancer. PMID:21088965

Splanchnic Vein Thrombosis in the Myeloproliferative Neoplasms.

PubMed

Akpan, Imo J; Stein, Brady Lee

2018-06-01

To review the epidemiology, diagnostic challenges, pathogenesis, and treatment strategies for patients with myeloproliferative neoplasm-associated splanchnic vein thrombosis. The epidemiology of myeloproliferative neoplasm-associated splanchnic vein thrombosis (MPN-SVT) has been well characterized. While typical MPN-associated thrombosis affects older patients and involves the arterial circulation, MPN-SVT mostly impacts younger women. An association with JAK2 V617F is well-known; recent studies have demonstrated only a weak association with CALR mutations. JAK inhibition may represent a novel treatment strategy, complementing anticoagulation, and management of portal hypertension. While the epidemiology has been well characterized, more work is needed to identify novel contributors to disease pathogenesis, beyond the JAK2 V617F mutation itself, and endothelial compromise. Testing for MPN mutations in the setting of non-cirrhotic SVT is commonplace; JAK2 V617F is the most likely to be identified. Testing for CALR or MPL mutations requires clinical judgement, though not unreasonable. The mainstay of therapy is indefinite anticoagulation; the role of direct oral anticoagulants is unclear. JAK inhibition may play a role in addressing associated splenomegaly and portal hypertension.

Three-dimensional printing for craniomaxillofacial regeneration.

PubMed

Gaviria, Laura; Pearson, Joseph J; Montelongo, Sergio A; Guda, Teja; Ong, Joo L

2017-10-01

Craniomaxillofacial injuries produce complex wound environments involving various tissue types and treatment strategies. In a clinical setting, care is taken to properly irrigate and stabilize the injury, while grafts are molded in an attempt to maintain physiological functionality and cosmesis. This often requires multiple surgeries and grafts leading to added discomfort, pain and financial burden. Many of these injuries can lead to disfigurement and resultant loss of system function including mastication, respiration, and articulation, and these can lead to acute and long-term psychological impact on the patient. A main causality of these issues is the lack of an ability to spatially control pre-injury morphology while maintaining shape and function. With the advent of additive manufacturing (three-dimensional printing) and its use in conjunction with biomaterial regenerative strategies and stem cell research, there is an increased potential capacity to alleviate such limitations. This review focuses on the current capabilities of additive manufacturing platforms, completed research and potential for future uses in the treatment of craniomaxillofacial injuries, with an in-depth discussion of regeneration of the periodontal complex and teeth.

Prevention and Management of Adverse Reactions Induced by Iodinated Contrast Media.

PubMed

Wu, Yi Wei; Leow, Kheng Song; Zhu, Yujin; Tan, Cher Heng

2016-04-01

Iodinated radiocontrast media (IRCM) is widely used in current clinical practice. Although IRCM is generally safe, serious adverse drug reactions (ADRs) may still occur. IRCM-induced ADRs may be subdivided into chemotoxic and hypersensitivity reactions. Several factors have been shown to be associated with an increased risk of ADRs, including previous contrast media reactions, history of asthma and allergic disease, etc. Contrast media with lower osmolality is generally recommended for at-risk patients to prevent ADRs. Current premedication prophylaxis in at-risk patients may reduce the risk of ADRs. However, there is still a lack of consensus on the prophylactic role of premedication. Contrast-induced nephropathy (CIN) is another component of IRCM-related ADRs. Hydration remains the mainstay of CIN prophylaxis in at-risk patients. Despite several preventive measures, ADRs may still occur. Treatment strategies for potential contrast reactions are also summarised in this article. This article summarises the pathophysiology, epidemiology and risk factors of ADRs with emphasis on prevention and treatment strategies. This will allow readers to understand the rationale behind appropriate patient preparation for diagnostic imaging involving IRCM.

Robotic devices and brain-machine interfaces for hand rehabilitation post-stroke.

PubMed

McConnell, Alistair C; Moioli, Renan C; Brasil, Fabricio L; Vallejo, Marta; Corne, David W; Vargas, Patricia A; Stokes, Adam A

2017-06-28

To review the state of the art of robotic-aided hand physiotherapy for post-stroke rehabilitation, including the use of brain-machine interfaces. Each patient has a unique clinical history and, in response to personalized treatment needs, research into individualized and at-home treatment options has expanded rapidly in recent years. This has resulted in the development of many devices and design strategies for use in stroke rehabilitation. The development progression of robotic-aided hand physiotherapy devices and brain-machine interface systems is outlined, focussing on those with mechanisms and control strategies designed to improve recovery outcomes of the hand post-stroke. A total of 110 commercial and non-commercial hand and wrist devices, spanning the 2 major core designs: end-effector and exoskeleton are reviewed. The growing body of evidence on the efficacy and relevance of incorporating brain-machine interfaces in stroke rehabilitation is summarized. The challenges involved in integrating robotic rehabilitation into the healthcare system are discussed. This review provides novel insights into the use of robotics in physiotherapy practice, and may help system designers to develop new devices.

Three-dimensional printing for craniomaxillofacial regeneration

PubMed Central

2017-01-01

Craniomaxillofacial injuries produce complex wound environments involving various tissue types and treatment strategies. In a clinical setting, care is taken to properly irrigate and stabilize the injury, while grafts are molded in an attempt to maintain physiological functionality and cosmesis. This often requires multiple surgeries and grafts leading to added discomfort, pain and financial burden. Many of these injuries can lead to disfigurement and resultant loss of system function including mastication, respiration, and articulation, and these can lead to acute and long-term psychological impact on the patient. A main causality of these issues is the lack of an ability to spatially control pre-injury morphology while maintaining shape and function. With the advent of additive manufacturing (three-dimensional printing) and its use in conjunction with biomaterial regenerative strategies and stem cell research, there is an increased potential capacity to alleviate such limitations. This review focuses on the current capabilities of additive manufacturing platforms, completed research and potential for future uses in the treatment of craniomaxillofacial injuries, with an in-depth discussion of regeneration of the periodontal complex and teeth. PMID:29142862

Humoral immunity in heart failure.

PubMed

Sarkar, Amrita; Rafiq, Khadija

2018-05-17

Cardiovascular disease (CVD) is a class of diseases that involve disorders of heart and blood vessels, including: hypertension, coronary heart disease, cerebrovascular disease, peripheral vascular disease, which finally lead to heart failure (HF). There are several treatments available all over the world, but still CVD and heart failure became the number one problem causing death every year worldwide. Both experimental and clinical studies have shown a role for inflammation in the pathogenesis of heart failure. This seems related to an imbalance between pro-inflammatory and anti-inflammatory cytokines. Cardiac inflammation is major pathophysiological mechanism operating in the failing heart, regardless of HF aetiology. Disturbances of the cellular and humoral immune system are frequently observed in heart failure. This review describes how B-cells play specific role in the heart failure states. There is an urgent need to identify novel therapeutic targets and develop advanced therapeutic strategies to combat the syndrome of HF. Understanding and describing the elements of the humoral immunity function are essential, and may suggest potential new treatment strategies. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Determining a sustainable and economically optimal wastewater treatment and discharge strategy.

PubMed

Hardisty, Paul E; Sivapalan, Mayuran; Humphries, Robert

2013-01-15

Options for treatment and discharge of wastewater in regional Western Australia (WA) are examined from the perspective of overall sustainability and social net benefit. Current practice in the state has typically involved a basic standard of treatment deemed to be protective of human health, followed by discharge to surface water bodies. Community and regulatory pressure to move to higher standards of treatment is based on the presumption that a higher standard of treatment is more protective of the environment and society, and thus is more sustainable. This analysis tests that hypothesis for Western Australian conditions. The merits of various wastewater treatment and discharge strategies are examined by quantifying financial costs (capital and operations), and by monetising the wider environmental and social costs and benefits of each option over an expanded planning horizon (30 years). Six technical treatment-disposal options were assessed at a test site, all of which met the fundamental criterion of protecting human health. From a financial perspective, the current business-as-usual option is preferred - it is the least cost solution. However, valuing externalities such as water, greenhouse gases, ecological impacts and community amenity, the status quo is revealed as sub-optimal. Advanced secondary treatment with stream disposal improves water quality and provides overall net benefit to society. All of the other options were net present value (NPV) negative. Sensitivity analysis shows that the favoured option outperforms all of the others under a wide range of financial and externality values and assumptions. Expanding the findings across the state reveals that moving from the identified socially optimal level of treatment to higher (tertiary) levels of treatment would result in a net loss to society equivalent to several hundred million dollars. In other words, everyone benefits from improving treatment to the optimum point. But society, the environment, and the Corporation are all worse off when treatment levels are pushed beyond what is economic and sustainable. Copyright © 2012 Elsevier Ltd. All rights reserved.

Freedom of Speech Newsletter, Volume 4, Number 1, October 1977.

ERIC Educational Resources Information Center

Kelley, Michael P., Ed.

This newsletter features an essay, "Anticipatory Democracy and Citizen Involvement: Strategies for Communication Education in the Future," which discusses strategies for improving citizen involvement and examines ways in which educators can prepare students for constructive citizen involvement. Notes on Speech Communication Association meetings…

Transitional polytherapy: tricks of the trade for monotherapy to monotherapy AED conversions.

PubMed

Garnett, William R; St Louis, Erik K; Henry, Thomas R; Bramley, Thomas

2009-06-01

The goal of epilepsy therapy is to help patients achieve seizure freedom without adverse effects. While monotherapy is preferable in epilepsy treatment, many patients fail a first drug due to lack of efficacy or failure to tolerate an initial medication, necessitating an alteration in therapy. Sudden changes between monotherapies are rarely feasible and sometimes deleterious given potential hazards of acute seizure exacerbation or intolerable adverse effects. The preferred method for converting between monotherapies is transitional polytherapy, a process involving initiation of a new antiepileptic drug (AED) and adjusting it toward a target dose while maintaining or reducing the dose of the baseline medication. A fixed-dose titration strategy of maintaining the baseline drug dose while titrating the new medication is preferable when breakthrough seizures are occurring and no adverse effects are present. However, a flexible titration strategy involving reduction of the baseline drug dose to ensure adequate tolerability of the new adjunctive medication is preferred when patients are already experiencing adverse effects. This article reviews pharmacokinetic considerations pertinent for ensuring successful transitional polytherapy with the standard and newer antiepileptic drugs. Practical consensus recommendations "from an expect panel (SPECTRA, Study by a Panel of Experts Considerations for Therapy Replacement and Antiepileptics) for a successful monotherapy" AED conversions are then summarized. Transitional polytherapy is most successful when clinicians appropriately manage the titration strategy and consider pharmacokinetic factors germane to the baseline and new adjunctive medication.

Actor modelling and its contribution to the development of integrative strategies for management of pharmaceuticals in drinking water.

PubMed

Titz, Alexandra; Döll, Petra

2009-02-01

Widespread presence of human pharmaceuticals in water resources across the globe is documented. While some, but certainly not enough, research on the occurrence, fate and effect of pharmaceuticals in water resources has been carried out, a holistic risk management strategy is missing. The transdisciplinary research project "start" aimed to develop an integrative strategy by the participation of experts representing key actors in the problem field "pharmaceuticals in drinking water". In this paper, we describe a novel modelling method, actor modelling with the semi-quantitative software DANA (Dynamic Actor Network Analysis), and its application in support of identifying an integrative risk management strategy. Based on the individual perceptions of different actors, the approach allows the identification of optimal strategies. Actors' perceptions were elicited by participatory model building and interviews, and were then modelled in perception graphs. Actor modelling indicated that an integrative strategy that targets environmentally-responsible prescription, therapy, and disposal of pharmaceuticals on one hand, and the development of environmentally-friendly pharmaceuticals on the other hand, will likely be most effective for reducing the occurrence of pharmaceuticals in drinking water (at least in Germany where the study was performed). However, unlike most other actors, the pharmaceutical industry itself does not perceive that the production of environmentally-friendly pharmaceuticals is an action that helps to achieve its goals, but contends that continued development of highly active pharmaceutical ingredients will help to reduce the occurrence of pharmaceuticals in the water cycle. Investment in advanced waste or drinking water treatment is opposed by both the wastewater treatment company and the drinking water supplier, and is not mentioned as appropriate by the other actors. According to our experience, actor modelling is a useful method to suggest effective and realisable integrative risk management strategies in complex problem fields that involve many societal actors.

Exercise, Manual Therapy, and Booster Sessions in Knee Osteoarthritis: Cost-Effectiveness Analysis From a Multicenter Randomized Controlled Trial.

PubMed

Bove, Allyn M; Smith, Kenneth J; Bise, Christopher G; Fritz, Julie M; Childs, John; Brennan, Gerard P; Abbott, J Haxby; Fitzgerald, G Kelley

2018-01-01

Limited information exists regarding the cost-effectiveness of rehabilitation strategies for individuals with knee osteoarthritis (OA). The study objective was to compare the cost-effectiveness of 4 different combinations of exercise, manual therapy, and booster sessions for individuals with knee OA. This economic evaluation involved a cost-effectiveness analysis performed alongside a multicenter randomized controlled trial. The study took place in Pittsburgh, Pennsylvania; Salt Lake City, Utah; and San Antonio, Texas. The study participants were 300 individuals taking part in a randomized controlled trial investigating various physical therapy strategies for knee OA. Participants were randomized into 4 treatment groups: exercise only (EX), exercise plus booster sessions (EX+B), exercise plus manual therapy (EX+MT), and exercise plus manual therapy and booster sessions (EX+MT+B). For the 2-year base case scenario, a Markov model was constructed using the United States societal perspective and a 3% discount rate for costs and quality-adjusted life years (QALYs). Incremental cost-effectiveness ratios were calculated to compare differences in cost per QALY gained among the 4 treatment strategies. In the 2-year analysis, booster strategies (EX+MT+B and EX+B) dominated no-booster strategies, with both lower health care costs and greater effectiveness. EX+MT+B had the lowest total health care costs. EX+B cost ${\\$}$1061 more and gained 0.082 more QALYs than EX+MT+B, for an incremental cost-effectiveness ratio of ${\\$}$12,900/QALY gained. The small number of total knee arthroplasty surgeries received by individuals in this study made the assessment of whether any particular strategy was more successful at delaying or preventing surgery in individuals with knee OA difficult. Spacing exercise-based physical therapy sessions over 12 months using periodic booster sessions was less costly and more effective over 2 years than strategies not containing booster sessions for individuals with knee OA. © 2017 American Physical Therapy Association

Treatment of Chronic Inflammatory Demyelinating Polyneuropathy: From Molecular Bases to Practical Considerations

PubMed Central

Ripellino, Paolo; Fleetwood, Thomas; Cantello, Roberto; Comi, Cristoforo

2014-01-01

Chronic inflammatory demyelinating polyneuropathy (CIDP) is an autoimmune disease of the peripheral nervous system, in which both cellular and humoral immune responses are involved. The disease is clinically heterogeneous with some patients displaying pure motor form and others also showing a variable degree of sensory dysfunction; disease evolution may also differ from patient to patient, since monophasic, progressive, and relapsing forms are reported. Underlying such clinical variability there is probably a broad spectrum of molecular dysfunctions that are and will be the target of therapeutic strategies. In this review we first explore the biological bases of current treatments and subsequently we focus on the practical management that must also take into account pharmacoeconomic issues. PMID:24527207

Use of percutaneous nephrostomy and ureteral stenting in management of ureteral obstruction

PubMed Central

Hsu, Linda; Li, Hanhan; Pucheril, Daniel; Hansen, Moritz; Littleton, Raymond; Peabody, James; Sammon, Jesse

2016-01-01

The management options for ureteral obstruction are diverse, including retrograde ureteral stent insertion or antegrade nephrostomy placement, with or without eventual antegrade stent insertion. There is currently no consensus on the ideal treatment or treatment pathway for ureteral obstruction owing, in part, to the varied etiologies of obstruction and diversity of institutional practices. Additionally, different clinicians such as internists, urologists, oncologists and radiologists are often involved in the care of patients with ureteral obstruction and may have differing opinions concerning the best management strategy. The purpose of this manuscript was to review available literature that compares percutaneous nephrostomy placement vs ureteral stenting in the management of ureteral obstruction from both benign and malignant etiologies. PMID:26981442

Recent mouse and rat methods for the study of experimental oral candidiasis.

PubMed

Costa, Anna C B P; Pereira, Cristiane A; Junqueira, Juliana C; Jorge, Antonio O C

2013-07-01

The Candida genus expresses virulence factors that, when combined with immunosuppression and other risk factors, can cause different manifestations of oral candidiasis. The treatment of mucosal infections caused by Candida and the elucidation of the disease process have proven challenging. Therefore, the study of experimentally induced oral candidiasis in rats and mice is useful to clarify the etiopathology of this condition, improve diagnosis, and search for new therapeutic options because the disease process in these animals is similar to that of human candidiasis lesions. Here, we describe and discuss new studies involving rat and mouse models of oral candidiasis with respect to methods for inducing experimental infection, methods for evaluating the development of experimental candidiasis, and new treatment strategies for oral candidiasis.

Interstitial cystitis intravesical therapy

PubMed Central

2017-01-01

Interstitial cystitis (IC) is a progressive bladder disorder that presents with symptoms of bladder urgency, frequency and pain. The aetiology of the disease remains uncertain, but it is postulated that there is an initial infective insult which damages the glycosaminoglycan (GAG) layer of the bladder urothelium. This defect allows an influx of ions, particularly potassium, which initiates an inflammatory reaction in the bladder wall, which incites the symptoms described above. Treatment initially involves behavioural and oral medication, with second line being intravesical instillation therapy. Treatment strategies focus on restoring lower urinary tract epithelial function, inhibiting neural activation, controlling allergies and relieving symptoms. In this review, current intravesical therapy will be discussed, as well as what lies on the horizon for intravesical therapy in IC. PMID:28791236

Inference in randomized trials with death and missingness.

PubMed

Wang, Chenguang; Scharfstein, Daniel O; Colantuoni, Elizabeth; Girard, Timothy D; Yan, Ying

2017-06-01

In randomized studies involving severely ill patients, functional outcomes are often unobserved due to missed clinic visits, premature withdrawal, or death. It is well known that if these unobserved functional outcomes are not handled properly, biased treatment comparisons can be produced. In this article, we propose a procedure for comparing treatments that is based on a composite endpoint that combines information on both the functional outcome and survival. We further propose a missing data imputation scheme and sensitivity analysis strategy to handle the unobserved functional outcomes not due to death. Illustrations of the proposed method are given by analyzing data from a recent non-small cell lung cancer clinical trial and a recent trial of sedation interruption among mechanically ventilated patients. © 2016, The International Biometric Society.

Osteochondroma of the fifth rib resulting in recurrent hemothorax.

PubMed

Patel, Mital; Bauer, Thomas W; Santoscoy, Thomas; Ilaslan, Hakan

2015-12-01

A 48-year-old man presented with recurrent spontaneous hemothoraces, which ultimately were found to be secondary to a pedunculated costal osteochondroma causing vascular injury. After initially undergoing endovascular coil embolization, he ultimately required segmental rib resection containing the offending lesion for definite treatment. Although a few cases of symptomatic costal osteochondromas have been reported in the literature, as far as we know, no previous reports have provided direct radiologic confirmation of active bleeding or the role of angiographic intervention. In this report, we highlight the importance of CT angiography in establishing a direct link between an osteochondroma and recurrent hemothorax. We also discuss the diagnostic imaging challenges associated with this condition and the use of a multidisciplinary treatment strategy involving both angiographic and operative management.

Individual Therapy With a Child of Divorced Parents.

PubMed

Jordan, Pauline H

2016-05-01

This article reviews the literature on divorce as a risk factor in children's psychological development; describes common themes expressed by children presenting in treatment; and highlights the unique challenges for the child therapist working with a child of divorce, particularly those with high parental conflict and court involvement. Then, using a case example, the article describes therapeutic strategies and a treatment structure that, consistent with the ethical guidelines of the American Psychological Association (2010), focuses on developing and maintaining the therapeutic relationship to support the psychological growth of the child. Finally, the article discusses the ethical challenges inherent in providing therapeutic intervention for this type of child and the implications for this type of therapeutic approach. © 2016 Wiley Periodicals, Inc.

Cutaneous Scar Prevention and Management

PubMed Central

Al-Shaqsi, Sultan; Al-Bulushi, Taimoor

2016-01-01

Cutaneous scarring is common after trauma, surgery and infection and occurs when normal skin tissue is replaced by fibroblastic tissue during the healing process. The pathophysiology of scar formation is not yet fully understood, although the degree of tension across the wound edges and the speed of cell growth are believed to play central roles. Prevention of scars is essential and can be achieved by attention to surgical techniques and the use of measures to reduce cell growth. Grading and classifying scars is important to determine available treatment strategies. This article presents an overview of the current therapies available for the prevention and treatment of scars. It is intended to be a practical guide for surgeons and other health professionals involved with and interested in scar management. PMID:26909210

Implication of the nutritional and nonnutritional factors in the context of preservation of cognitive performance in patients with dementia/depression and Alzheimer disease.

PubMed

Aliev, Gjumrakch; Ashraf, Ghulam Md; Kaminsky, Yury G; Sheikh, Ishfaq Ahmed; Sudakov, Sergey K; Yakhno, Nikolay N; Benberin, Valery V; Bachurin, Sergey O

2013-11-01

It has been postulated that Alzheimer disease (AD) is a systemic process, which involves multiple pathophysiological factors. A combination of pharmacotherapy and nonpharmacological interventions has been proposed to treat AD and other dementia. The nonpharmacological interventions include but are not limited to increasing sensory input through physical and mental activities, in order to modify cerebral blood flow and implementing nutritional interventions such as diet modification and vitamins and nutraceuticals therapy to vitalize brain functioning. This article highlights the recent research findings regarding novel treatment strategies aimed at modifying natural course of the disease and delaying cognitive decline through simultaneous implementation of pharmacological and nonpharmacological modulators as standardized treatment protocols.

Estimating the impact of adding C-reactive protein as a criterion for lipid lowering treatment in the United States.

PubMed

Woloshin, Steven; Schwartz, Lisa M; Kerin, Kevin; Welch, H Gilbert

2007-02-01

There is growing interest in using C-reactive protein (CRP) levels to help select patients for lipid lowering therapy--although this practice is not yet supported by evidence of benefit in a randomized trial. To estimate the number of Americans potentially affected if a CRP criteria were adopted as an additional indication for lipid lowering therapy. To provide context, we also determined how well current lipid lowering guidelines are being implemented. We analyzed nationally representative data to determine how many Americans age 35 and older meet current National Cholesterol Education Program (NCEP) treatment criteria (a combination of risk factors and their Framingham risk score). We then determined how many of the remaining individuals would meet criteria for treatment using 2 different CRP-based strategies: (1) narrow: treat individuals at intermediate risk (i.e., 2 or more risk factors and an estimated 10-20% risk of coronary artery disease over the next 10 years) with CRP > 3 mg/L and (2) broad: treat all individuals with CRP > 3 mg/L. Analyses are based on the 2,778 individuals participating in the 1999-2002 National Health and Nutrition Examination Survey with complete data on cardiac risk factors, fasting lipid levels, CRP, and use of lipid lowering agents. The estimated number and proportion of American adults meeting NCEP criteria who take lipid-lowering drugs, and the additional number who would be eligible based on CRP testing. About 53 of the 153 million Americans aged 35 and older meet current NCEP criteria (that do not involve CRP) for lipid-lowering treatment. Sixty-five percent, however, are not currently being treated, even among those at highest risk (i.e., patients with established heart disease or its risk equivalent)-62% are untreated. Adopting the narrow and broad CRP strategies would make an additional 2.1 and 25.3 million Americans eligible for treatment, respectively. The latter strategy would make over half the adults age 35 and older eligible for lipid-lowering therapy, with most of the additionally eligible (57%) coming from the lowest NCEP heart risk category (i.e., 0-1 risk factors). There is substantial underuse of lipid lowering therapy for American adults at high risk for coronary disease. Rather than adopting CRP-based strategies, which would make millions more lower risk patients eligible for treatment (and for whom treatment benefit has not yet been demonstrated in a randomized trial), we should ensure the treatment of currently defined high-risk patients for whom the benefit of therapy is established.

The Importance of Implementation Strategy in Scaling Up Xpert MTB/RIF for Diagnosis of Tuberculosis in the Indian Health-Care System: A Transmission Model

PubMed Central

Salje, Henrik; Andrews, Jason R.; Deo, Sarang; Satyanarayana, Srinath; Sun, Amanda Y.; Pai, Madhukar; Dowdy, David W.

2014-01-01

Background India has announced a goal of universal access to quality tuberculosis (TB) diagnosis and treatment. A number of novel diagnostics could help meet this important goal. The rollout of one such diagnostic, Xpert MTB/RIF (Xpert) is being considered, but if Xpert is used mainly for people with HIV or high risk of multidrug-resistant TB (MDR-TB) in the public sector, population-level impact may be limited. Methods and Findings We developed a model of TB transmission, care-seeking behavior, and diagnostic/treatment practices in India and explored the impact of six different rollout strategies. Providing Xpert to 40% of public-sector patients with HIV or prior TB treatment (similar to current national strategy) reduced TB incidence by 0.2% (95% uncertainty range [UR]: −1.4%, 1.7%) and MDR-TB incidence by 2.4% (95% UR: −5.2%, 9.1%) relative to existing practice but required 2,500 additional MDR-TB treatments and 60 four-module GeneXpert systems at maximum capacity. Further including 20% of unselected symptomatic individuals in the public sector required 700 systems and reduced incidence by 2.1% (95% UR: 0.5%, 3.9%); a similar approach involving qualified private providers (providers who have received at least some training in allopathic or non-allopathic medicine) reduced incidence by 6.0% (95% UR: 3.9%, 7.9%) with similar resource outlay, but only if high treatment success was assured. Engaging 20% of all private-sector providers (qualified and informal [providers with no formal medical training]) had the greatest impact (14.1% reduction, 95% UR: 10.6%, 16.9%), but required >2,200 systems and reliable treatment referral. Improving referrals from informal providers for smear-based diagnosis in the public sector (without Xpert rollout) had substantially greater impact (6.3% reduction) than Xpert scale-up within the public sector. These findings are subject to substantial uncertainty regarding private-sector treatment patterns, patient care-seeking behavior, symptoms, and infectiousness over time; these uncertainties should be addressed by future research. Conclusions The impact of new diagnostics for TB control in India depends on implementation within the complex, fragmented health-care system. Transformative strategies will require private/informal-sector engagement, adequate referral systems, improved treatment quality, and substantial resources. Please see later in the article for the Editors' Summary PMID:25025235

The Network Model of Depression as a Basis for New Therapeutic Strategies for Treating Major Depressive Disorder in Parkinson’s Disease

PubMed Central

D’Ostilio, Kevin; Garraux, Gaëtan

2016-01-01

The high prevalence of major depressive disorder in people with Parkinson’s disease (PD), its negative impact on health-related quality of life and the low response rate to conventional pharmacological therapies call to seek innovative treatments. Here, we review the new approaches for treating major depressive disorder in patients with PD within the framework of the network model of depression. According to this model, major depressive disorder reflects maladaptive neuronal plasticity. Non-invasive brain stimulation (NIBS) using high frequency repetitive transcranial magnetic stimulation (rTMS) over the prefrontal cortex has been proposed as a feasible and effective strategy with minimal risk. The neurobiological basis of its therapeutic effect may involve neuroplastic modifications in limbic and cognitive networks. However, the way this networks reorganize might be strongly influenced by the environment. To address this issue, we propose a combined strategy that includes NIBS together with cognitive and behavioral interventions. PMID:27148016

Targeting lipid metabolism of cancer cells: A promising therapeutic strategy for cancer.

PubMed

Liu, Qiuping; Luo, Qing; Halim, Alexander; Song, Guanbin

2017-08-10

One of the most important metabolic hallmarks of cancer cells is deregulation of lipid metabolism. In addition, enhancing de novo fatty acid (FA) synthesis, increasing lipid uptake and lipolysis have also been considered as means of FA acquisition in cancer cells. FAs are involved in various aspects of tumourigenesis and tumour progression. Therefore, targeting lipid metabolism is a promising therapeutic strategy for human cancer. Recent studies have shown that reprogramming lipid metabolism plays important roles in providing energy, macromolecules for membrane synthesis, and lipid signals during cancer progression. Moreover, accumulation of lipid droplets in cancer cells acts as a pivotal adaptive response to harmful conditions. Here, we provide a brief review of the crucial roles of FA metabolism in cancer development, and place emphasis on FA origin, utilization and storage in cancer cells. Understanding the regulation of lipid metabolism in cancer cells has important implications for exploring a new therapeutic strategy for management and treatment of cancer. Copyright © 2017 Elsevier B.V. All rights reserved.

Posttraumatic stress following pediatric injury: update on diagnosis, risk factors, and intervention.

PubMed

Kassam-Adams, Nancy; Marsac, Meghan L; Hildenbrand, Aimee; Winston, Flaura

2013-12-01

After pediatric injury, transient traumatic stress reactions are common, and about 1 in 6 children and their parents develop persistent posttraumatic stress (PTS) symptoms that are linked to poorer physical and functional recovery. Meta-analytic studies identify risk factors for persistent PTS, including preinjury psychological problems, peritrauma fear and perceived life threat, and posttrauma factors such as low social support, maladaptive coping strategies, and parent PTS symptoms. There is growing prospective data indicating that children's subjective appraisals of the injury and its aftermath influence PTS development. Secondary prevention of injury-related PTS often involves parents and focuses on promoting adaptive child appraisals and coping strategies. Web-based psychoeducation and targeted brief early intervention for injured children and their parents have shown a modest effect, but additional research is needed to refine preventive approaches. There is a strong evidence base for effective psychological treatment of severe and persistent PTS via trauma-focused cognitive behavioral therapy; evidence is lacking for psychopharmacological treatment. Pediatric clinicians play a key role in preventing injury-related PTS by providing "trauma-informed" pediatric care (ie, recognizing preexisting trauma, addressing acute traumatic stress reactions associated with the injury event, minimizing potentially traumatic aspects of treatment, and identifying children who need additional monitoring or referral).

Need of righteous attitudes towards eradication of hepatitis C virus infection in Latin America

PubMed Central

Panduro, Arturo; Roman, Sonia

2016-01-01

Over the last few years, we have expanded our knowledge on numerous facets of the hepatitis C virus (HCV). Beginning with its discovery and viral life cycle, its impact on health, the development of liver disease and currently, effective antiviral treatments. The latter point has become of great interest throughout the developed world, where the possible eradication of HCV through specific strategies to reach all HCV-infected people has been announced. However, this scenario is very different in the countries of Latin America (LA), in which < 2% of infected patients requiring treatment have access to HCV medications. It has been estimated that at least ten million Latin Americans may be infected with HCV. Despite the numbers, viral hepatitis does not seem to be considered a health problem in this region of the world. This reality poses a challenge for politicians and governments of these countries, as well as to the pharmaceutical industry, the medical practitioners, and academics in LA. In this editorial, we state the need for alterations in the attitudes of the integral players involved in this situation. A recognition shift could help to create preventive strategies of viral hepatitis and to advocate for accessibility to new HCV treatments. PMID:27298556

Who cares? Pathways to psychiatric care for young people experiencing a first episode of psychosis.

PubMed

Lincoln, C V; McGorry, P

1995-11-01

The authors reviewed the literature to better understand pathways to psychiatric care among young persons experiencing a first episode of psychosis. Because no discrete body of literature exists about how young people with psychotic illness gain access to psychiatric services, the authors examined three related areas: illness recognition, help-seeking, and referral pathways. Automated and manual searches of primarily medical and psychological sources from 1977 to 1995 were conducted. The review found evidence of delay in obtaining early treatment among young people with an emerging psychosis, although comparisons between studies are difficult. Early psychiatric intervention is believed to significantly aid recovery and is an increasingly important clinical issue. Recognizing psychiatric illness is problematic for professionals and nonprofessionals. Understanding of help seeking by patients experiencing a first psychotic episode and of their referral pathways is limited. Taken together, studies suggest factors affecting access to treatment but provide neither sufficient empirical information nor an adequate conceptual framework to better target secondary prevention strategies. Formulation of a pathways-to-care model appears to offer a useful way of understanding mental health care use. Exploration of consumer experiences would enrich the model. Strategies to reduce treatment delay could then be developed and evaluated. Increased consumer involvement might help ensure that services are better tailored to patients' needs.

Review of the treatment of psoriatic arthritis with biological agents: choice of drug for initial therapy and switch therapy for non-responders.

PubMed

D'Angelo, Salvatore; Tramontano, Giuseppina; Gilio, Michele; Leccese, Pietro; Olivieri, Ignazio

2017-01-01

Psoriatic arthritis (PsA) is a heterogeneous chronic inflammatory disease with a broad clinical spectrum and variable course. It can involve musculoskeletal structures as well as skin, nails, eyes, and gut. The management of PsA has changed tremendously in the last decade, thanks to an earlier diagnosis, an advancement in pharmacological therapies, and a wider application of a multidisciplinary approach. The commercialization of tumor necrosis factor inhibitors (adalimumab, certolizumab pegol, etanercept, golimumab, and infliximab) as well as interleukin (IL)-12/23 (ustekinumab) and IL-17 (secukinumab) inhibitors is representative of a revolution in the treatment of PsA. No evidence-based strategies are currently available for guiding the rheumatologist to prescribe biological drugs. Several international and national recommendation sets are currently available with the aim to help rheumatologists in everyday clinical practice management of PsA patients treated with biological therapy. Since no specific biological agent has been demonstrated to be more effective than others, the drug choice should be made according to the available safety data, the presence of extra-articular manifestations, the patient's preferences (e.g., administration route), and the drug price. However, future studies directly comparing different biological drugs and assessing the efficacy of treatment strategies specific for PsA are urgently needed.

Protons pump inhibitor treatment and lower gastrointestinal bleeding: Balancing risks and benefits.

PubMed

Lué, Alberto; Lanas, Angel

2016-12-28

Proton pump inhibitors (PPIs) represent a milestone in the treatment of acid-related diseases, and are the mainstay in preventing upper gastrointestinal bleeding in high-risk patients treated with nonsteroidal anti-inflammatory drugs (NSAIDs) or low-dose aspirin. However, this beneficial effect does not extend to the lower gastrointestinal tract. PPIs do not prevent NSAID or aspirin-associated lower gastrointestinal bleeding (LGB). PPIs may increase both small bowel injury related to NSAIDs and low-dose aspirin treatment and the risk of LGB. Recent studies suggested that altering intestinal microbiota by PPIs may be involved in the pathogenesis of NSAID-enteropathy. An increase in LGB hospitalization rates may occur more frequently in older patients with more comorbidities and are associated with high hospital resource utilization, longer hospitalization, and increased mortality. Preventive strategies for NSAID and aspirin-associated gastrointestinal bleeding should be directed toward preventing both upper and lower gastrointestinal damage. Future research should be directed toward identifying patients at low-risk for gastrointestinal events associated with the use of NSAIDs or aspirin to avoid inappropriate PPI prescribing. Alternatively, the efficacy of new pharmacologic strategies should be evaluated in high-risk groups, with the aim of reducing the risk of both upper and lower gastrointestinal bleeding in these patients.

Helicobacter pylori and Gastric Mucosa-associated Lymphoid Tissue (MALT) Lymphoma: Updated Review of Clinical Outcomes and the Molecular Pathogenesis.

PubMed

Suzuki, Hidekazu; Saito, Yoshimasa; Hibi, Toshifumi

2009-06-01

In most H. pylori-positive patients, gastric low-grade mucosa-associated lymphoid tissue (MALT) lymphomas regress both endoscopically and histopathologically after H. pylori eradication, but no factors that can be predictive of the response to the eradication have been definitively identified, and there is little information on how to determine the optimal observation period before additional treatment can be started. Here, clinical studies dealing with the diagnosis and treatment of gastric MALT lymphomas and H. pylori published during the last 5 years were systematically reviewed, and studies identifying the molecular approaches involved in the pathogenesis were summarized. Most of the clinical studies indicate a favorable effect of H. pylori eradication on the clinical outcome of gastric MALT lymphomas. Some studies suggest the necessity of additional treatment in nonresponders to H. pylori eradication, while others suggest the adoption of a watch-and-wait strategy. The molecular characteristics of MALT lymphomas could play an important role in prognostic prediction and the selection of further therapeutic intervention after the eradication. This updated review of gastric MALT lymphomas illustrates the potential efficacy of H. pylori eradication in tumor remission, but further molecular characterization is necessary to establish the most suitable therapeutic strategy for patients who do not respond to eradication.

Systemic Delivery of Salmonella Typhimurium Transformed with IDO shRNA Enhances Intratumoral Vector Colonization and Suppresses Tumor Growth

PubMed Central

Blache, Celine A.; Manuel, Edwin R.; Kaltcheva, Teodora I.; Wong, Andrea N.; Ellenhorn, Joshua D.I.; Blazar, Bruce R.; Diamond, Don J.

2012-01-01

Generating antitumor responses through the inhibition of tumor-derived immune suppression represents a promising strategy in the development of cancer immunotherapeutics. Here we present a strategy incorporating delivery of the bacterium Salmonella typhimurium (ST), naturally tropic for the hypoxic tumor environment, transformed with an shRNA plasmid against the immunosuppressive molecule indoleamine 2,3-dioxygenase 1 (shIDO). When systemically delivered into mice, shIDO silences host IDO expression and leads to massive intratumoral cell death that is associated with significant tumor infiltration by polymorphonuclear neutrophils (PMNs). shIDO-ST treatment causes tumor cell death independently of host IDO and adaptive immunity, which may have important implications for use in immunosuppressed cancer patients. Further, shIDO-ST treatment increases reactive oxygen species (ROS) produced by infiltrating PMNs and conversely, PMN immunodepletion abrogates tumor control. Silencing of host IDO significantly enhances ST colonization, suggesting that IDO expression within the tumor controls the immune response to ST. In summary, we present a novel approach to cancer treatment that involves the specific silencing of tumor-derived IDO that allows for the recruitment of ROS-producing PMNs, which may act primarily to clear ST infection, but in the process, also induces apoptosis of surrounding tumor tissue resulting in a vigorous anti-tumor effect. PMID:23090116

Effects of nanosecond pulsed electric fields (nsPEFs) on the human fungal pathogen Candida albicans: an in vitro study

NASA Astrophysics Data System (ADS)

Guo, Jinsong; Dang, Jie; Wang, Kaile; Zhang, Jue; Fang, Jing

2018-05-01

Candida albicans is the leading human fungal pathogen that causes many life-threatening infections. Notably, the current clinical trial data indicate that Candida species shows the emerging resistance to anti-fungal drugs. The aim of this study was to evaluate the antifungal effects of nanosecond pulsed electric fields (nsPEFs) as a novel drug-free strategy in vitro. In this study, we investigated the inactivation and permeabilization effects of C. albicans under different nsPEFs exposure conditions (100 pulses, 100 ns in duration, intensities of 20, 40 kV cm‑1). Cell death was studied by annexin-V and propidium iodide staining. The changes of intracellular Ca2+ concentration after nsPEFs treatment were observed using Fluo-4 AM. Results show that C. albicans cells and biofilms were both obviously inhibited and destroyed after nsPEFs treatment. Furthermore, C. albicans cells were significantly permeabilized after nsPEFs treatment. Additionally, nsPEFs exposure led to a large amount of DNA and protein leakage. Importantly, nsPEFs induced a field strength-dependent apoptosis in C. albicans cells. Further experiments revealed that Ca2+ involved in nsPEFs induced C. albicans apoptosis. In conclusion, this proof-of-concept study provides a potential alternative drug-free strategy for killing pathogenic Candida species.

Engineering novel synthetic strategy to develop mesocarbon microbeads for multi-functional applications

NASA Astrophysics Data System (ADS)

Chaudhary, Anisha; Teotia, Satish; Kumar, Rajeev; Ramesha, K.; Dhakate, Sanjay R.; Kumari, Saroj

2018-04-01

To assess the challenge of affordable technology, present synthetic strategies can be extended to new low-cost synthesis and processing methods that have potential to tailor the properties of the materials. Here we report, a novel method for the synthesis of mesocarbon microbeads (MCMB) through a pre-processing involved pyrolysis technique. The resulting MCMB is compressed into a product and effects of heat treatment temperature on different properties of MCMB is studied. The use of MCMB for the electromagnetic interference (EMI) shielding is new and hence, the effect of heat treatment temperature on EMI shielding effectiveness is studied in X-band. It is observed that EMI shielding effectiveness increases to ‑39.6 dB on increasing the heat treatment temperature. The high conductivity of MCMB plate heat treated upto 2500 °C contributes to highly conducting networks. Additionally, to investigate the electrochemical performance of MCMB as an anode material for lithium ion batteries, 2500 °C heat treated MCMB powder is used to fabricate the electrode. The MCMB electrode exhibits high discharge capacity of 345 mAh g‑1 with a stable capacity for over 50 cycles and good rate capability. Thus, MCMB synthesized by this novel approach can be used for the development of high performance anode materials for Li-ion batteries.

Forest fuel reduction alters fire severity and long-term carbon storage in three Pacific Northwest ecosystems.

PubMed

Mitchell, Stephen R; Harmon, Mark E; O'Connell, Kari E B

2009-04-01

Two forest management objectives being debated in the context of federally managed landscapes in the U.S. Pacific Northwest involve a perceived trade-off between fire restoration and carbon sequestration. The former strategy would reduce fuel (and therefore C) that has accumulated through a century of fire suppression and exclusion which has led to extreme fire risk in some areas. The latter strategy would manage forests for enhanced C sequestration as a method of reducing atmospheric CO2 and associated threats from global climate change. We explored the trade-off between these two strategies by employing a forest ecosystem simulation model, STANDCARB, to examine the effects of fuel reduction on fire severity and the resulting long-term C dynamics among three Pacific Northwest ecosystems: the east Cascades ponderosa pine forests, the west Cascades western hemlock-Douglas-fir forests, and the Coast Range western hemlock-Sitka spruce forests. Our simulations indicate that fuel reduction treatments in these ecosystems consistently reduced fire severity. However, reducing the fraction by which C is lost in a wildfire requires the removal of a much greater amount of C, since most of the C stored in forest biomass (stem wood, branches, coarse woody debris) remains unconsumed even by high-severity wildfires. For this reason, all of the fuel reduction treatments simulated for the west Cascades and Coast Range ecosystems as well as most of the treatments simulated for the east Cascades resulted in a reduced mean stand C storage. One suggested method of compensating for such losses in C storage is to utilize C harvested in fuel reduction treatments as biofuels. Our analysis indicates that this will not be an effective strategy in the west Cascades and Coast Range over the next 100 years. We suggest that forest management plans aimed solely at ameliorating increases in atmospheric CO2 should forgo fuel reduction treatments in these ecosystems, with the possible exception of some east Cascades ponderosa pine stands with uncharacteristic levels of understory fuel accumulation. Balancing a demand for maximal landscape C storage with the demand for reduced wildfire severity will likely require treatments to be applied strategically throughout the landscape rather than indiscriminately treating all stands.

Screening for increased cardiometabolic risk in primary care: a systematic review

PubMed Central

den Engelsen, Corine; Koekkoek, Paula S; Godefrooij, Merijn B; Spigt, Mark G; Rutten, Guy E

2014-01-01

Background Many programmes to detect and prevent cardiovascular disease (CVD) have been performed, but the optimal strategy is not yet clear. Aim To present a systematic review of cardiometabolic screening programmes performed among apparently healthy people (not yet known to have CVD, diabetes, or cardiometabolic risk factors) and mixed populations (apparently healthy people and people diagnosed with risk factor or disease) to define the optimal screening strategy. Design and setting Systematic review of studies performed in primary care in Western countries. Method MEDLINE, Embase, and CINAHL databases were searched for studies screening for increased cardiometabolic risk. Exclusion criteria were studies designed to assess prevalence of risk factors without follow-up or treatment; without involving a GP; when fewer than two risk factors were considered as the primary outcome; and studies constrained to ethnic minorities. Results The search strategy yielded 11 445 hits; 26 met the inclusion criteria. Five studies (1995–2012) were conducted in apparently healthy populations: three used a stepwise method. Response rates varied from 24% to 79%. Twenty-one studies (1967–2012) were performed in mixed populations; one used a stepwise method. Response rates varied from 50% to 75%. Prevalence rates could not be compared because of heterogeneity of used thresholds and eligible populations. Observed time trends were a shift from mixed to apparently healthy populations, increasing use of risk scores, and increasing use of stepwise screening methods. Conclusion The optimal screening strategy in primary care is likely stepwise, in apparently healthy people, with the use of risk scores. Increasing public awareness and actively involving GPs might facilitate screening efficiency and uptake. PMID:25267047

Enhancing the role of private practitioners in tuberculosis prevention and care activities in India.

PubMed

Anand, Tanu; Babu, Ranjith; Jacob, Anil G; Sagili, Karuna; Chadha, Sarabjit S

2017-01-01

India accounts for the highest number of incident tuberculosis (TB) cases globally. Hence, to impact the TB incidence world over, there is an urgent need to address and accelerate TB control activities in the country. Nearly, half of the TB patients first seek TB care in private sector. However, the participation of private practitioners (PPs) has been patchy in TB prevention and care and distrust exists between public and private sector. PPs usually have varied diagnostic and treatment practices that are inadequate and amplify the risk of drug resistance. Hence, their regulation and involvement as key stakeholders are important in TB prevention and care in India if we are to achieve TB control at global level. However, there remain certain barriers and gaps, which are preventing their upscaling. The current paper aims to discuss the status of private sector involvement in TB prevention and care in India. The paper also discusses the strategies and initiatives taken by the government in this regard as evidence shows that the involvement of private sector in co-opting directly observed treatment short-course (DOTS) helps to enhance case finding and treatment outcomes; it improves the accessibility of quality TB care with greater geographic coverage. Besides public-private mix, DOTS has been found more cost-effective and reduces financial burden of patients. The paper also offers to present some more solutions both at policy and program level for upscaling the engagement of PPs in the national TB control program.

The natural history of hereditary motor and sensory neuropathy with proximal dominant involvement (HMSN-P) in 97 Japanese patients.

PubMed

Fujisaki, Natsumi; Suwazono, Shugo; Suehara, Masahito; Nakachi, Ryo; Kido, Miwako; Fujiwara, Yoshihisa; Oshiro, Saki; Tokashiki, Takashi; Takashima, Hiroshi; Nakagawa, Masanori

2018-02-01

Hereditary motor and sensory neuropathy with proximal dominant involvement (HMSN-P) is a motor and sensory neuronopathy with autosomal dominant inheritance, adult onset, slowly progressive course, and is associated with TRK-fused gene (TFG) mutation. At advanced stages, respiratory failure and dysphagia becomes life-threatoning, and patients typically die by their 70s. Although there is currently no evidence for effective treatment, a therapy may be found by elucidation of the function of TFG. Recently its pathomechanism has been proposed to be associated with abnormalities in protein transfer from the endoplasmic reticulum. Such pathomechanisms might involve a similar process in amyotrophic lateral sclerosis; thus, its pathomechanisms and treatment strategy might make it a good model for neurodegenerative disorders. It is of great value to clarify the natural history of HMSN-P, in oder to judge the treatment effect. By evaluating 97 patients (79 out of 97 were examined and all confirmed with p.Pro 285 Leu mutation) in this study, it was confirmed that this disease follows a uniform course in the earlier stages, and there are individual differences in the onset between 20 and 30 years. Such uniformity might be due to the proposed single gene abnormality. At advanced stages, there are larger individual differences in the progression, but the reasons for these are unknown. Longer survival might be achieved with a better care for respiratory failure and dysphagia if such cares were undertaken at appropriate times.