Delayed recovery of serum immunoglobulin G is a poor prognostic marker in patients with follicular lymphoma treated with rituximab maintenance

Abstract

Clinical trials involving various treatment schedules for rituximab maintenance have been conducted for patients with follicular lymphoma (FL) and have not confirmed their impact on serum immunoglobulin (sIg) levels until the completion of maintenance. However, the long-term use of rituximab is a concern because of circulating plasma cell-depletion risk, suggesting that the mechanism of change in sIg levels after RM has not been determined. Additionally, the relationship between host humoral immunity and the prognosis of patients with B cell malignancies has not been determined. We retrospectively investigated data from 213 patients with FL from a single institute who achieved at least a partial response with rituximab, cyclophosphamide, vincristine, and prednisolone with or without doxorubicin. Of these, 166 patients underwent RM with a median period of 1.6 years. A significantly delayed recovery of sIgG levels was observed in the maintenance group until 3 years after RM in comparison to the observation group. A multivariate analysis showed that a sIgG level of < 718 mg/dl 1 year after RM was an independent predictor for poor progression-free survival (PFS) (hazard ratio, 2.3; P = 0.04). Therefore, the sIgG levels scarcely recovered and were significantly delayed after RM, leading to shorter PFS in patients with FL.

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Lacrimal drainage anomalies in congenital rubella syndrome

http://ift.tt/2iUZItT

Water-Rich Biomimetic Composites with Abiotic Self-Organizing Nanofiber Network

Abstract

Load-bearing soft tissues, e.g., cartilage, ligaments, and blood vessels, are made predominantly from water (65–90%) which is essential for nutrient transport to cells. Yet, they display amazing stiffness, toughness, strength, and deformability attributed to the reconfigurable 3D network from stiff collagen nanofibers and flexible proteoglycans. Existing hydrogels and composites partially achieve some of the mechanical properties of natural soft tissues, but at the expense of water content. Concurrently, water-rich biomedical polymers are elastic but weak. Here, biomimetic composites from aramid nanofibers interlaced with poly(vinyl alcohol), with water contents of as high as 70–92%, are reported. With tensile moduli of ≈9.1 MPa, ultimate tensile strains of ≈325%, compressive strengths of ≈26 MPa, and fracture toughness of as high as ≈9200 J m⁻², their mechanical properties match or exceed those of prototype tissues, e.g., cartilage. Furthermore, with reconfigurable, noncovalent interactions at nanomaterial interfaces, the composite nanofiber network can adapt itself under stress, enabling abiotic soft tissue with multiscale self-organization for effective load bearing and energy dissipation.

Water-rich biomimetic composites from aramid nanofibers interlaced with poly(vinyl alcohol) emulate the collagen–proteoglycan network in load-bearing soft tissues. The hydrogen bonding between stiff nanofibers and soft polymers affords synergistic stiffening and toughening, allowing the nanofiber network to self-organize under stress for effective load bearing and energy dissipation. Their mechanics, biocompatibility, and high water content permit utilization as load-bearing biomaterials and for other applications including durable high transport rate membranes membranes in water desalination, fuel cells, and batteries.

http://ift.tt/2yZEqWV

Music for Speech and Language Development in Early Childhood Populations

Abstract

Research in the area of expressive communication and speech and language in particular is growing, especially in the area of early childhood. The purpose of this paper is to review research pertaining to the speech and language domain in young children and to posit treatment implications for music therapists who may use this information in order to enhance their evidence-based approach to the population. This examination includes music therapy and non-music therapy peer-reviewed publications that may be applicable to music therapy clinical practice. Three areas emerged: neuroscience findings, non-music-based speech and language research, and clinical music applications, which are then discussed in relation to music therapy clinical practice.

http://ift.tt/2moJ0YB

Music, Neuroscience, and Communication: Introduction to the Focus Area

In 2013, Shannon de l'Etoile and I guest-edited a special issue of Music Therapy Perspectives that was focused on the neuroscience of sensorimotor applications in music therapy. The May 2013 issue presented an overview of music and the brain by renowned cognitive psychologist Daniel Levitin, and several authors presented the importance of rhythm for timing of motor movement (Grahn & Watson, 2013; Thaut, 2013). This provided a foundation for considering the impact of music and rhythm on motor movements. Furthermore, music therapy clinicians presented considerations for music therapy applications addressing sensorimotor skills in rehabilitation (Conklyn & Bethoux, 2013; Lindaman & Abiru, 2013; Rice & Johnson, 2013; Whitall & McCombe Walker, 2013) and habilitation (Kwak & Kim, 2013; LaGasse & Hardy, 2013).

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Therapeutic Singing Protocols for Addressing Acquired and Degenerative Speech Disorders in Adults

Abstract

The ability to communicate and make oneself understood is integral to a person's quality of life. It affects social interaction, educational and vocational opportunities, and ultimately independence and sense of self. Unfortunately, speech production is often impaired as a result of neurological damage (e.g., traumatic brain injury, stroke) or disorders (e.g., Parkinson's disease). There are many similarities and shared neural mechanisms between speech and singing. For example, both singing and speech utilize rhythm, pitch variation, tempo, dynamics, articulation, and respiratory support. Music therapists manipulate these elements of music when addressing therapeutic goals for people with neurogenic speech disorders. Many clinical protocols to address speech disorders in adults have now been published to guide clinical practice in music therapy. This paper summarizes existing music therapy and singing-based protocols used to address commonly occurring acquired or degenerative speech disorders, namely dysarthria, dysphonia, dysprosody, and apraxia of speech. We examine individual and group therapy protocols used in medical and community settings for people with neurogenic speech disorders caused by traumatic brain injury, stroke, spinal cord injury, and Parkinson's disease. We highlight the strengths and limitations of these protocols and make recommendations for clinical practice.

http://ift.tt/2yYELsS

Honoring Clinicians’ Voices

Music Therapy Perspectives (MTP) has been referred to as the "clinician's journal," serving as the place for music therapists and music therapy students to learn about innovative ways of working, new trends in care, and research findings that are applicable to clinical work. The profession owes a debt of gratitude to Michael McGuire as the first editor of MTP and also to Brian Wilson for creating an accessible platform for clinical work to have primacy. Our field is growing at a phenomenal rate, and our current Editor-in-Chief, Dr. Tony Meadows, has expanded the scope of the journal to include relevant and timely theoretical and scholarly articles. As the journal continues to evolve, we are vigilant in remaining connected to our clinical readership, many of whom are working within areas of practice that are fairly new, such as trauma-informed approaches and neurologically based treatment. Balancing the journal's mission of serving clinicians against offering a venue for fresh visions of research (arts-based research and single-subject design, for example) leads us to an iterative process of reflection.

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AMTA Graduate Student Research Award Effects of Hope-Based Music Therapy on Hospitalized Patients on a Blood and Marrow Transplant Unit: A Convergent Parallel Mixed-Methods Pilot Study

Abstract

Background

Patients undergoing Blood and Marrow Transplantation (BMT) are particularly susceptible to psychological distress due to the demanding nature of BMT procedures. Hope is a malleable (Weis & Speridakos, 2011) and multidimensional construct (Kim, Schwartz-Barcott, & Zucker, 2006) that can impact a patient's psychological health. Extant research on hope with cancer patients has promoted psychological interventions to foster and maintain hope, but has been conducted almost exclusively within the field of oncology nursing.

Related Literature

While research supports music therapy interventions that address pain, anxiety, depression, isolation, mood disturbance, motivation, and fatigue in BMT patients (Boldt, 1996; Cassileth, Vickers, & Magill, 2003; Fredenburg & Silverman, 2014a, 2014b; Rosenow & Silverman, 2014; Sahler, Hunter, & Liesveld, 2003), little attention has been given to interventions that enhance patient resources in ways that may offset or mitigate psychological distress. Hope-based music therapy interventions might broaden findings within the oncology nursing literature linking levels of hope with improved psychological functioning, coping skills, and quality of life (Felder, 2004; Herth, 1989, 1992, 2001; Molassiotis, Van Den Akker, Milligan, Goldman, & Boughton, 1996).

Objective

The purpose of this convergent parallel mixed-methods pilot study was to target hope by adapting an existing hope intervention to music therapy treatment with patients on a BMT unit. The research questions guiding this study were: Are there between-group differences in patient hope resultant of a two-dose hope-based music therapy intervention in adult patients on a BMT unit? How do adult patients on a BMT unit perceive hope and psychological health impacted by the hope-based music therapy intervention?

Methods

Patients (N = 10) were randomly assigned to experimental or wait-list control conditions, and all patients completed the Herth Hope Index (Herth, 1992) supplemented with an 11-point Likert-Type Pain Scale at pre- and posttest. Experimental participants engaged in a two-session individualized music therapy treatment consisting of patient-preferred live music chosen from a hope-based song menu coupled with therapeutic dialogue that was adapted from the Hope Intervention Program (Herth, 2001). At the conclusion of the intervention, experimental participants also took part in an individual semi-structured interview in an attempt to understand their experiences and perceptions of how music therapy may have impacted hope. Thematic analysis, following the six-step procedure identified by Braun and Clarke (2006), was used to analyze qualitative data.

Results

There was no significant between-group difference in hope or pain at pretest. Posttest analyses utilizing Mann-Whitney U tests revealed a significant between-group difference (p = .035) in measures of hope, with participants in the experimental condition (M = 44.00, SD = 2.12) demonstrating higher hope than participants in the control condition (M = 38.90, SD = 3.71). Although not statistically significant, there was a slight tendency for a decrease in pre- to posttest pain for the experimental condition but not for the control condition. Qualitative analyses resulted in three emerging themes: 1. Hope-based music therapy provides opportunities for positive experiences, including comfort and interpersonal connection; 2. Hope-based music therapy facilitates personal depth though self-awareness and self-identity; and 3. Hope-based music therapy provides a platform to discuss and confront hope, including motivations for and obstacles to hope.

Conclusions

Although generalization is limited by a small sample, preliminary evidence supports that hope-based music therapy can be a beneficial intervention for patients undergoing BMT. Qualitative data reinforced and provided depth to these quantitative results, revealing that hope-based music therapy elicited positive experiences, comfort, and interpersonal connection; acted as a platform to discuss hope; and supported self-awareness and self-identity.

Implications for Clinical Practice

Implications for clinical practice include integration of hope-based treatment goals and objectives in care of BMT and oncology patients, with additional clinical work warranted to inform hope-based treatments with other hospitalized medical patients. Patients were able to exercise repertoire choices within their individual sessions from a hope-based song menu, with some patients choosing to hear the same song in sessions on both days one and two. As patients verbalized that supplying a song menu was helpful for them, song menus may facilitate choice and coping in music therapy sessions based upon patient-preferred live music.

Implications for Future Research

Suggestions for future research include measuring maintenance of hope gains, exploring hope in a longitudinal context, examining levels of hope at various stages of illness and treatment, and investigating larger dosages of music therapy treatment and the subsequent impact on patient hope. As behavior synchrony can result from emotional contagion (Hatfield, Cacioppo, & Rapson, 1994), future research might explore such contagion in a context of hope as it occurs between patients, their care supporters, and hospital roommates in various adult medical settings. Such inquiry may also include structuring sessions to focus not only on patients, but also on care partners. Additionally, future researchers may examine application of hope-based music therapy with procedures outside BMT, including solid organ transplantation.

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“Big Up West London Crew”: One Man’s Journey within a Community Rap/Music Therapy Group

Abstract

This case study describes work undertaken within an NHS early intervention mental health service in the UK, focusing on the therapeutic use of "freestyle" and original rap. In particular, it uses material and analysis pertaining to one individual who formed part of an open group for clients in the community. The specific role of this form of therapy is detailed, addressing the aims of the work relating to the setting and background of the client, and outlines the rationale for the use of an empowerment-based model of working. The clinical material is analyzed from a psychodynamic perspective, with a particular emphasis on the development of the therapeutic relationship and the use of rap as a therapeutic intervention, taking into consideration stylistic and cultural connotations of the genre and Hip Hop culture.

http://ift.tt/2mnVOhX

Understanding the Influence of Music on Emotions: A Historical Review

Music has long been thought to influence human emotions. There is significant interest among researchers and the public in understanding music-induced emotions; in fact, a common motive for engaging with music is its emotion-inducing capabilities (Juslin & Sloboda, 2010). Traditionally, the influence of music on emotions has been described as dichotomous. The Greeks viewed it as either mimesis, a representation of an external reality, or catharsis, a purification of the soul through an emotional experience (Cook & Dibben, 2010). This type of dichotomous viewpoint has persisted under various labels, such as formalist versus absolutist, and referential versus expressionist (Meyer, 1956). However, these perspectives all emerged from musicology. Outside musicology, the scientific study of emotions was intermittent and, until recently, references to music's effect on emotions were rare (Sloboda & Juslin, 2010). Since the 1990s, there has been increased interest in studying music-induced emotions, particularly in psychology (Juslin & Sloboda, 2010). This interest extends to the music therapy profession as well. For example, a professional music therapist in the United States is required to be able to develop and implement music therapy experiences designed to focus on emotion-related treatment goals, such as the ability to empathize, and the client's overall affect, mood, and emotions (Certification Board for Music Therapists [CBMT], 2015), and must apply knowledge of music-based emotional responses (American Music Therapy Association [AMTA], 2013). Given the increased interest in psychology and the clinical implications for the music therapist, it seems timely to analyze and reflect on how the understanding of music-induced emotions has evolved in order to support current and future research and clinical practice. As current understanding is built upon prior knowledge, a historical review can serve to examine previous directions and help inform future study (Hanson-Abromeit & Davis, 2007). Thus, the purpose of this inquiry was to provide a historical overview of prominent theories of music and emotion and connect them to current understanding. More specifically, the objectives were:

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Making Sense of Today’s Electronic Music Technology Resources for Music Therapy

Abstract

As a way of staying current with electronic music technologies, this article describes four categories of these technologies and provides evaluative considerations to help clinicians efficiently and effectively understand potential applications. Through vignettes of music therapy practice, this article will elaborate on the clinical use of these software, stand-alone products, electronic keyboards, and iPads/tablets categories. Specific therapist action steps for evaluating the usefulness of these products are provided for each category. A summary section details nine considerations for clinicians when determining which resources could be used in their work.

http://ift.tt/2yZaSsi

Keyboard Playing as a Hand Exercise for Patients with Subacute Stroke

Abstract

Recent reports show that MIDI keyboard playing can improve upper-limb functions in neurorehabilitation, but little attention has been paid to this type of intervention with stroke patients in the subacute stage. The purpose of this study was to investigate the effects of keyboard-playing intervention that targeted hand dexterity of subacute stroke patients. A total of 17 subacute stroke patients participated in twelve 30-minute sessions over six weeks. The intervention included repetitive individuated, sequential, and simultaneous key-pressing to increase independent finger movements and strength. Of the four hand-function tests administered in this study, tip pinch in hand grip and pinch strength test and Box and Block Test (BBT) results showed the most significant improvement, indicating the largest effect sizes (0.785 for hand grip and pinch strength test and 0.840 for BBT). Better hand dexterity for subacute stroke patients may be achieved through repetitive key-pressing motions during keyboard playing by exercising the intrinsic and extrinsic flexor muscles primarily involved in the key-pressing motion. Overall, this study supports keyboard playing as a promising therapeutic intervention in subacute stroke rehabilitation.

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Obtaining Competencies with Self-Determination Theory: The Music Therapy Internship

Abstract

The purpose of this paper is to provide a conceptual framework that creates an environment of optimal learning for music therapy interns by supporting the psychological needs that facilitate intrinsic motivation, learning, and well-being. To accomplish this, supervisors will use self-determination theory (SDT) as a lens to view the training experience. The linear model presented matches (a) time, (b) emotional needs, (c) SDT psychological needs, (d) music therapy professional competencies, and (e) transitional roles. Employing the proposed model will permit supervisors to be proactive in addressing intern areas of need and growth. What follows is a review of literature on music therapy internship and SDT, rational for model development, and strategies for practice implementation.

http://ift.tt/2yZIAxO

Assessment-Based Small-Group Music Therapy Programming for Individuals with Dementia and Alzheimer’s Disease: A Multi-Year Clinical Project

Abstract

Research examining the use of music and music therapy to treat individuals with Alzheimer's and dementia indicates that active music-making and personalized therapeutic interactions can have a positive effect on reducing symptoms, maintaining function, and improving overall well-being. Many music therapists, however, report working in the role of a recreation therapist, with little opportunity to treat in individualized, assessment-based small-group settings. This article describes a clinical project in which a small-group model of therapy for individuals with dementia and Alzheimer's disease was developed in an academic setting and then piloted in eldercare community settings. The model utilizes gradual scaffolding of skills over time, rather than the more common theme-based approach. Participants demonstrated not only improvement in social, emotional, language, and musical functioning, but also new learning. The challenges of application when working as a solitary therapist in a facility are discussed, and a model for facilities is offered.

http://ift.tt/2mrH6qu

A Conceptual Framework for Group Processing of Lyric Analysis Interventions in Music Therapy Mental Health Practice

Abstract

Although lyric analysis is a common music therapy intervention in mental health, limited clinical information is available that specifically focuses on the processing questions used during implementation. Based on Kees and Jacobs's (1990) group exercise processing model, and contextualized within a cognitive-behavioral orientation, this lyric analysis framework provides structure and assists music therapy students and young clinicians in the beginning stages of planning, implementing, and evaluating lyric analysis interventions. This conceptual framework includes five levels of goal-directed questions: foundation (i.e., process the music itself), reflection (i.e., reflect on participant responses), group process (i.e., discuss the effect on group process), personal insights (i.e., reflect on participants' personal insights), and transfer (i.e., transfer new insights to their lives). Music therapy students and beginning clinicians may create a priori questions based on needs, goals, and characteristics of the clients, group, music, and therapist, and move through the five levels based on client responses and clinical decisions.

http://ift.tt/2yZatGi

When Home Feels Familiar But Yet So Foreign—The Professional Readjustment Experiences of Returning Internationally-Trained Singaporean Music Therapists

Abstract

There is no formal music therapy training available in Singapore. All Singaporean music therapists are trained in a socio-cultural context different from their home country, resulting in readjustment issues when they return. This phenomenological study, comprising interviews with four Singaporean music therapists, found that the music therapists' readjustment back to Singapore was marked by transition blues as they took on responsibilities of a professional with added reverse culture shock. The different socio-cultural contexts between their country of training and Singapore also meant that clients sometimes responded in an unexpected manner, finding some music therapy approaches less effective in Singapore. Participants also struggled to fit their professional aspirations with the local environment, yet felt at home as they understood the social context upon return as music therapists. Embracing advocacy, finding supportive networks, and being adaptable while finding ways to stay true to one's professional beliefs helped overcome challenges of readjustment.

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Study-Abroad in Music Therapy: Cultural Immersion as a Form of Self-Experience

Abstract

Music therapists are expected to attain and maintain a broad range of multicultural competencies. In order to do so, a group of students participated in a study-abroad program in music therapy, involving classroom learning, community building, a clinical placement, and attendance at an international conference. A sample of these students participated in a qualitative interview study to explore what they learned. Results suggest that the program led to changes in students' views of music therapy practice, the music therapy profession, and their definition of music therapy. The profession of music therapy is thus viewed as culturally situated, underscoring the importance of cultural self-awareness. The discussion contextualizes the results of these learning experiences using a Piagetian framework. Recommendations for music therapy faculty and organizations are drawn from the study findings.

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Investigating the Effectiveness of a Developmental, Individual Difference, Relationship-Based (DIR) Improvisational Music Therapy Program on Social Communication for Children with Autism Spectrum Disorder

Abstract

The purpose of this study was to examine the effectiveness of improvisational music therapy carried out within a DIRFloortime framework in addressing the individual social communication needs of children with Autism Spectrum Disorder (ASD). Participants included four children enrolled in a therapeutic day school, 4–8 years of age, and diagnosed with ASD. Each child participated in twenty-four 30-minute individual DIR-based improvisational music therapy sessions over the course of 13 weeks. The Functional Emotional Assessment Scale (FEAS) was used to evaluate changes in social communication skills. Results indicated improvements in areas of self-regulation, engagement, behavioral organization, and two-way purposeful communication.

http://ift.tt/2yYEDJU

Connecting to Self and Other through Electroacoustic Composition and Performance: A Case Study

Abstract

This case study explored music therapy sessions with Ben, a frail, emotionally guarded, but intellectually curious adult male in his mid-fifties, diagnosed with PTSD. Sessions concentrated on helping Ben improve expressive communication through the study, exploration, creation, and performance of avant-garde electroacoustic music. Integrative music therapy sessions took place at a psychosocial club in New York City and were aimed at helping Ben improve awareness of feeling-states and expressivity, and to begin to develop deeper relationships within his therapeutic community. A discovery-oriented approach (Mahrer, 1988) was used as the method of both data-gathering and textual analysis. The author used the data to explore his own subjective understanding of (a) Ben's verbal expressivity while surveying avant-garde electroacoustic music, (b) the nonverbal aspects of Ben's experimental timbre-centered music-making experience, (c) Ben's original electroacoustic composition via musical analysis, and (d) audience reactions to Ben's timbre-centered electroacoustic composition. These data suggest that Ben was able to express feeling-states, mostly nonverbal, and experience a positive client-therapist relationship within the therapeutic process, as well as receive support and encouragement from the therapeutic community at the psychosocial club.

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Neurokinin 1 receptor antagonists in the prevention of chemotherapy-induced nausea and vomiting: focus on fosaprepitant

Future Oncology, Ahead of Print.


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Nivolumab in recurrent/metastatic head and neck cancers

Future Oncology, Ahead of Print.


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Image-guided surgery and therapy for lung cancer: a critical review

Future Oncology, Ahead of Print.


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Current Role for Biomarkers in Clinical Diagnosis of Alzheimer Disease and Frontotemporal Dementia

Abstract

Purpose of review Alzheimer's disease (AD) and frontotemporal dementia can often be diagnosed accurately with careful clinical history, cognitive testing, neurological examination, and structural brain MRI. However, there are certain circumstances wherein detection of specific biomarkers of neurodegeneration or underlying AD pathology will impact the clinical diagnosis or treatment plan. We will review the currently available biomarkers for AD and frontotemporal dementia (FTD) and discuss their clinical importance.

Recent findings With the advent of ¹⁸F-labeled tracers that bind amyloid plaques, amyloid PET is now clinically available for the detection of amyloid pathology and to aid in a biomarker-supported diagnosis of AD or mild cognitive impairment (MCI) due to AD. It is not yet possible to test for the specific FTD pathologies (tau or TDP-43); however, a diagnosis of FTD may be "imaging supported" based upon specific MRI or FDG-PET findings. Cerebrospinal fluid measures of amyloid-beta, total-tau, and phospho-tau are clinically available and allow detection of both of the cardinal pathologies of AD: amyloid and tau pathology.

Summary It is appropriate to pursue biomarker testing in cases of MCI and dementia when there remains diagnostic uncertainty and the result will impact diagnosis or treatment. Practically speaking, due to the rising prevalence of amyloid positivity with advancing age, measurement of biomarkers in cases of MCI and dementia is most helpful in early-onset patients, patients with atypical clinical presentations, or when considering referral for AD clinical trials.

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Which Individuals To Choose To Update the Reference Population? Minimizing the Loss of Genetic Diversity in Animal Genomic Selection Programs

Genomic selection is commonly used in livestock and increasingly in plant breeding. Relying on phenotypes and genotypes of a reference population, genomic selection allows performance prediction for young individuals having only genotypes. This is expected to achieve fast high genetic gain but with a potential loss of genetic diversity. Existing methods to conserve genetic diversity depend mostly on the choice of the breeding individuals. In this study we propose a modification of the reference population composition to mitigate diversity loss. Since the high cost of phenotyping is the limiting factor for genomic selection our findings are of major economic interest. This study aims to answer the following questions: How would decisions on the reference population affect the breeding population? How to best select individuals to update the reference population and balance maximizing genetic gain and minimizing loss of genetic diversity? We investigated three updating strategies for the reference population: random, truncation and optimal contribution strategies. Optimal contribution maximizes genetic merit for a fixed loss of genetic diversity. A French Montbéliarde dairy cattle population with 50K SNP chip genotypes and simulations over ten generations were used to compare these different strategies using milk production as the trait of interest. Candidates were selected to update the reference population. Prediction bias and both genetic merit and diversity were measured. Changes in the reference population composition slightly affected the breeding population. Optimal contribution strategy appeared to be an acceptable compromise to maintain both genetic gain and diversity in the reference and the breeding populations.

http://ift.tt/2hvRz2l

Correction to: Abstracts

Abstract

In Oral Free Paper Sessions, the first-author name was missing from the authorship group originally listed for Abstract OFP-04-012 (page S14), entitled "Differentiating primary pulmonary squamous cell carcinoma from squamous cell carcinoma of the cervix metastatic to the lung: Histological and immunohistochemistry study".

http://ift.tt/2joQqdm

Pharmacokinetics and drug-drug interactions of lopinavir/ritonavir administered with first and second-line antituberculosis drugs in HIV-infected children treated for multidrug-resistant tuberculosis [PublishAheadOfPrint]

Background Lopinavir/ritonavir forms the backbone of current first-line antiretroviral regimens in young HIV-infected children. As multidrug-resistant (MDR) tuberculosis (TB) frequently occurs in young children in high-burden TB settings, it is important to identify potential interactions between MDR-TB treatment and lopinavir/ritonavir. We describe the pharmacokinetics of and potential drug-drug interactions between lopinavir/ritonavir and routine drugs used for MDR-TB treatment in HIV-infected children.

Methods A combined population pharmacokinetic model was developed to jointly describe the pharmacokinetics of lopinavir and ritonavir in 32 HIV-infected children (16 on MDR-TB treatment with combinations of high-dose isoniazid, pyrazinamide, ethambutol, ethionamide, terizidone, a fluoroquinolone, and amikacin: and 16 without TB), who were established on a lopinavir/ritonavir-containing antiretroviral regimen.

Results One-compartment models with first-order absorption and elimination for both lopinavir and ritonavir were combined into an integrated model. The dynamic inhibitory effect of ritonavir concentration on lopinavir clearance was described using an Imax model. Even after adjusting for the effect of body weight with allometric scaling, large variability in lopinavir and ritonavir exposure was detected, together with strong correlations between the pharmacokinetic parameters of lopinavir and ritonavir. MDR-TB treatment did not have a significant effect on the bioavailability, clearance, or absorption rate constants of lopinavir or ritonavir. Most children (81% of MDR-TB; 88% of controls) achieved therapeutic lopinavir trough concentrations (>1 mg/L).

Conclusions No significant effect was found on key pharmacokinetic parameters of lopinavir or ritonavir when co-administered with routine drugs used for MDR-TB. These findings should be considered in the context of large inter-patient variability and the modest sample size.

http://ift.tt/2hrGGuM

Ritonavir-boosted protease inhibitors but not cobicistat appear safe in HIV-positive patients ingesting dabigatran [PublishAheadOfPrint]

Patients with human immunodeficiency virus (HIV) have a near normal life expectancy and as a result are experiencing common age-related medical conditions (e.g., atrial fibrillation) and polypharmacy.1,2 ...

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Fungal prophylaxis with a gastro-resistant posaconazole tablet for patients with hematological malignancies: final result of the POSANANTES study. [PublishAheadOfPrint]

Posaconazole is an antifungal drug used in both prophylaxis and treatment of invasive fungal infections. Its oral formulation requires therapeutic drug monitoring. To overcome gastric acidity, a gastro-resistant posaconazole tablet has recently been developed. POSANANTES was a prospective non interventional study that aimed to monitor plasma concentration trough level (Cmin) of posaconazole tablets used prophylactically in patients with hematological malignancies. Fifty patients were included. Group A (n= 31) included patients receiving induction chemotherapy for myeloid malignancies and group B (n=19) included patients treated for graft versus host disease after allogeneic hematopoietic stem cells transplantation. In multivariate analysis, female sex, group B and evaluation of Cmin at D8 (versus any other day planned by the analysis) were associated with a higher Cmin, while diarrhea was associated with a lower Cmin (p<0.05). Thirty-four percent (n=17) of all included patients had to prematurely stop treatment, mainly in group A. In conclusion, this real-life prospective study showed good absorption of posaconazole tablets prophylaxis in patients with hematological malignancies even though this strategy was somewhat limited due to the high number of patients in group A who had to stop their treatment in an untimely fashion.

http://ift.tt/2hrGFqI

Emergence of chromosome borne colistin resistance gene mcr-1 in clinical isolates of Klebsiella pneumoniae from India [PublishAheadOfPrint]

Transmissible colistin resistance gene, mcr-1 has breached the one of the last line of defense for treatment of infections caused by carbapenem-resistant Enterobacteriaceae....

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A promising anti-prion trimethoxychalcone binds to the globular domain of PrPC and changes its cellular location [PublishAheadOfPrint]

The search for anti-prion compounds has been encouraged by the fact that transmissible spongiform encephalopathies (TSEs) share molecular mechanisms with more prevalent neurodegenerative pathologies, such as Parkinson's and Alzheimer's diseases. Cellular prion protein conversion into protease-resistant forms (PrP^Res or PrP^Sc) is a critical step in the development of TSEs, thus being one of the main targets in the screening for anti-prion compounds. In this work, three trimethoxychalcones (J1, J8, J20) and one oxadiazole (Y17), previously identified in vitro as potential anti-prion compounds, were evaluated through different approaches in order to gain inferences about their mechanism of action. None of them changed PrP^C mRNA levels in N2a cells as shown by RT-qPCR. Among them, J8 and Y17 were effective in RT-QuIC reactions using rodent rPrP^23--231 as substrate and PrP^Sc seeds from hamster and human brain. However, when rPrP^90--231, which lacks the N-terminal domain, was used as substrate, only J8 remained effective, indicating that this region is important for Y17 activity, while J8 seems to interact with PrP^C globular domain. J8 also reduced the fibrillation of mouse rPrP^23--231 seeded with in vitro-produced fibrils. Furthermore, most of the compounds decreased the amount of PrP^C on N2a cell surface by trapping this protein in the endoplasmic reticulum. Based on these results, we hypothesize that J8, a non-toxic promising anti-prion compound as previously shown, may act by different mechanisms, since its efficacy is attributable not only to the PrP conversion inhibition, but also to reduction of PrP^C content on the cell surface.

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Outcomes of vancomycin plus a {beta}-lactam versus vancomycin only for the treatment of methicillin-resistant Staphylococcus aureus bacteremia [PublishAheadOfPrint]

The objective of this retrospective study was to compare the rates of treatment failure, which was a composite of clinical and microbiologic failure, of patients receiving vancomycin and a β-lactam to those receiving vancomycin only for MRSA bacteremia. Patients 16 to 89 years of age with MRSA bacteremia admitted to a university-affiliated hospital from January 1^st, 2014 to December 31^st, 2016 were screened for study inclusion. Patients were eligible if they received >48 hours of vancomycin and a β-lactam (combination group) or vancomycin only (standard group) within 48 hours following bacteremia onset. 182 patients were screened: 47 were included in the standard group and 63 in the combination group. The combination group had a higher baseline body mass index (29.2 ± 8.0 kg/m² vs 25.8 ± 7.1 kg/m², p=0.022), acute physiologic assessment and chronic health evaluation-II (APACHE-II) score (median [interquartile range], 21 (15-26) vs 16 (10-22), p=0.003), and incidence of septic shock (31.8% vs 14.9%, p=0.047). Using multivariate analysis, combination therapy was the only variable that decreased treatment failures (odds ratio [95% confidence interval], 0.337 [0.142 to 0.997]), while vancomycin MIC >1 mg/L and male gender increased treatment failures (4.018 [1.297 to 12.444] and 2.971 [1.040 to 8.488], respectively). 30-day mortality rates (15.0% vs 14.9%, p=1.000) and incidence of adverse drug events (19.1% vs 23.4%, p=0.816) were not statistically different between the combination and standard groups. Combination therapy of vancomycin with a β-lactam led to significantly fewer treatment failures than vancomycin monotherapy for MRSA bacteremia.

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Use of Pharmacokinetic and Pharmacodynamic Analyses to Determine the Optimal Fixed Dosing Regimen of Iclaprim for Treatment of Serious Gram-Positive Infections [PublishAheadOfPrint]

Iclaprim is a bacterial dihydrofolate reductase inhibitor that is currently being evaluated in two Phase 3 trials for the treatment of patients with acute bacterial skin and skin structure infections (ABSSSI). Prior animal infection models studies suggest that the pharmacokinetic and pharmacodynamics (PK/PD) drivers for efficacy are area under the curve from 0-24 hours at steady state (AUC_0-24hss), AUC/minimum inhibitory concentration (MIC), and time above the MIC during the dosing interval (T > MIC) while QTc prolongation was associated to maximal concentration at steady state (C_maxss) in a thorough QTc Phase 1 study. Using PK data collected from 470 patients from the previously conducted Phase 3 complicated skin and skin infection (cSSSI) trials, population PK modeling and Monte Carlo simulation were used to identify a fixed iclaprim dosage regimen for its ongoing Phase 3 ABSSSI studies that maximized AUC_0-24hss, AUC/MIC, and T > MIC while minimizing probability of a C_maxss ≥ 800 ng/mL relative to the cSSSI regimen of 0.8 mg/kg intravenously infused over 0.5 hours, every 12 hours. The MCS analyses indicated that administration of 80 mg as a two hour infusion every 12 hours provides a 28%, 28%, and 32% increase in AUC_0-24hss, AUC,/MIC, & T > MIC, respectively, compared to the 0.8 mg/kg cSSSI regimen, while decreasing the probability of C_maxss ≥ 800 ng/mL by 9%. Based on PK/PD analyses, iclaprim 80 mg administered over two hours every 12 hours was selected as the dosing scheme for its subsequent Phase 3 clinical trials.

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Synthesis of Methyl 4-(7-hydroxy-4,4,8-trimethyl-3-oxabicyclo[3.3.1]nonan-2-yl)benzoate and their evaluation as anti-leishmanial: Synergistic effect with Miltefosine [PublishAheadOfPrint]

In perpetuation of our interest in oxabicyclic compounds as potent anti-leishmanial, the present work deals with the chemical synthesis of new oxabicyclic derivative Methyl 4-(7-hydroxy-4,4,8-trimethyl-3-oxabicyclo[3.3.1]nonan-2-yl)benzoate (PS-207). This oxabicyclic derivative showed good anti-leishmanial effect on the parasite, both on promastigote and amastigote stages. The mode of parasitic death after PS-207 seems to be apoptotic. Interestingly, the combination of PS-207 with low dose of miltefosine showed synergistic effect against the parasite.

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Development of protective immunity in New Zealand White rabbits challenged with Bacillus anthracis spores and treated with antibiotics and obiltoxaximab, a monoclonal antibody against protective antigen [PublishAheadOfPrint]

Recommended management of inhalational anthrax, a high-priority bioterrorist threat, includes antibiotics and antitoxins. Obiltoxaximab, a chimeric monoclonal antibody against anthrax Protective Antigen (PA) is licensed under the U.S. Food and Drug Administration's (FDA's) Animal Rule for treatment of inhalational anthrax. Because of spore latency, disease re-emergence after treatment cessation is a concern and there is a need to understand development of endogenous protective immune responses following antitoxin-containing anthrax treatment regimens. Here, acquired protective immunity was examined in NZW rabbits challenged with a targeted lethal dose of B. anthracis spores and treated with antibiotics, obiltoxaximab or a combination of both. Survivors of the primary challenge were re-challenged 9 month later, and monitored for survival. Survival rates after primary and re-challenge, for controls and animals treated with obiltoxaximab, levofloxacin or a combination of both were 0, 65, 100, 95% and 0, 100, 95, 89%, respectively. All surviving immune animals had circulating antibodies to PA and serum toxin neutralizing titers prior to re-challenge. Following re-challenge, systemic bacteremia and toxemia were not detected in most animals and levels of circulating anti-PA IgG titers increased starting 5 days post re-challenge. We conclude that treatment with obiltoxaximab, alone or combined with antibiotics, significantly improves survival of rabbits that received a lethal inhalation B. anthracis spore challenge and does not interfere with development of immunity. Survivors of primary challenge are protected against re-exposure, have rare incidents of systemic bacteremia and toxemia, and have evidence of an anamnestic response.

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Activity of Simulated Human Dosage Regimens of Meropenem and Vaborbactam against Carbapenem-resistant Enterobacteriaceae in an In Vitro Hollow Fiber Model [PublishAheadOfPrint]

The objective of these studies was to evaluate the exposures of meropenem and vaborbactam that would produce antibacterial activity and prevent resistance development in carbapenem-resistant, Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacteriaceae strains when tested at an inocula of 10⁸ CFU/mL. Thirteen K. pneumoniae isolates, three Enterobacter cloacae isolates, and one Escherichia coli isolate were examined in an in vitro hollow fiber model over 32 hours. Simulated dosage regimens of meropenem 1-2 g with vaborbactam 1-2 g, meropenem administered every 8 hours by 3 hour infusion based on Phase 1 or Phase 3 patient pharmacokinetic data were studied in the model. Meropenem 2 g in combination with vaborbactam 2 g was bactericidal against K. pneumoniae, E. cloacae, and E. coli strains with meropenem-vaborbactam MICs of up to 8 mg/L. When the vaborbactam exposure was adjusted to the levels observed in patients enrolled in Phase 3 trials (24 h free AUC ~ 550 vs 320 mg*h/L in the Phase 1 studies), meropenem 2 g with vaborbactam 2 g was also bactericidal against strains with meropenem-vaborbactam MICs of 16 mg/L. In addition, this level of vaborbactam, also suppressed the development of resistance observed using Phase 1 exposures. In this pharmacodynamic model, exposures similar to meropenem 2 g in combination with vaborbactam 2 g administered every 8 hours by 3 hour infusion in Phase 3 trials produced antibacterial activity and suppressed the development of resistance against carbapenem resistant, KPC producing strains of Enterobacteriaceae.

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The frequency and mechanism of spontaneous resistance to sulbactam combined with the novel {beta}-lactamase inhibitor ETX2514 in clinical isolates of Acinetobacter baumannii [PublishAheadOfPrint]

The novel diazabicyclooctenone ETX2514 is a potent, broad spectrum serine β-lactamase inhibitor that restores sulbactam activity against resistant Acinetobacter baumannii. The frequency of spontaneous resistance to sulbactam-ETX2514 in clinical isolates was found to be 7.6x10^-10 to <9.0x10^-10 at 4x MIC and mapped to residues near the active site of PBP3. Purified mutant PBP3 proteins demonstrated reduced affinity for sulbactam. In a sulbactam-sensitive isolate, resistance also mapped to stringent response genes associated with resistance to PBP2 inhibitors, suggesting that, in addition to β-lactamase inhibition, ETX2514 may also enhance sulbactam activity in A. baumannii via inhibition of PBP2.

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Copper ions and coordination complexes as novel carbapenem adjuvants [PublishAheadOfPrint]

Carbapenem-resistant Enterobacteriaceae are an urgent threat to global human health. These organisms produce β-lactamases with carbapenemase activity, such as the metallo-β-lactamase NDM-1, which is notable due to its association with mobile genetic elements and the lack of a clinically useful inhibitor. Here we examined the ability of copper to inhibit the activity of NDM-1 and explored the potential of a copper coordination complex as a mechanism to efficiently deliver copper as an adjuvant in clinical therapeutics. An NDM-positive Escherichia coli isolate, MS6192, was cultured from the urine of a patient with urinary tract infection. MS6192 was resistant to antibiotics from multiple classes, including diverse β-lactams (penicillins, cephalosporins, and carbapenems), aminoglycosides and fluoroquinolones. However, in the presence of copper (range 0-2 mM), the susceptibility of MS6192 to the carbapenems ertapenem and meropenem increased significantly. In standard checkerboard assays, copper decreased the MIC of ertapenem and meropenem against MS6192 in a dose-dependent manner, suggesting a synergistic mode of action. To examine the inhibitory effect of copper in the absence of other β-lactamases, the bla_NDM-1 gene from MS6192 was cloned and expressed in a recombinant E. coli K-12 strain. Analysis of cell-free extracts prepared from this strain revealed copper directly inhibits NDM-1 activity, and this was further confirmed using purified recombinant NDM-1. Finally, delivery of copper at a low concentration of 10 μM using the FDA-approved coordination complex copper-pyrithione sensitised MS6192 to ertapenem and meropenem in a synergistic manner. Overall, this work demonstrates the potential use of copper-coordination complexes as novel carbapenemase adjuvants.

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What is resistance? Impact of phenotypic versus molecular drug resistance testing on multi- and extensively drug-resistant tuberculosis therapy [PublishAheadOfPrint]

Rapid and accurate drug-susceptibility testing (DST) is essential for the treatment of multi- and extensively drug-resistant tuberculosis (M/XDR-TB). We compared the utility of genotypic DST assays with phenotypic DST (pDST) using BACTEC 960 MGIT or Löwenstein-Jensen to construct M/XDR-TB treatment regimens for a cohort of 25 consecutive M/XDR-TB patients and 15 possible anti-TB drugs.

Genotypic DST results from Cepheid GeneXpert MTB/RIF (Xpert) and line probe assays (LPAs: Hain GenoType MTBDRplus 2.0 and MTBDRsl 2.0)] and whole genome sequencing (WGS) were translated into individual algorithm-derived treatment regimens for each patient. We further analysed if discrepancies between the various methods were due to flaws in the genotypic or phenotypic test using MIC results.

Compared with pDST, the average agreement in the number of drugs prescribed in 'genotypic' regimens ranged from just 49% (95% CI 39-59%) for Xpert and 63% (95% CI 56-70%) for LPAs to 93% (95% CI 88-98%) for WGS. Only the WGS regimens did not comprise any drugs to which pDST showed resistance. Importantly, MIC testing revealed that pDST likely underestimated the true rate of resistance for key drugs (rifampicin, levofloxacin, moxifloxacin, and kanamycin) because critical concentrations (CCs) were too high.

WGS can be used to rule-in resistance even in M/XDR strains with complex resistance patterns, but pDST for some drugs is still needed to confirm susceptibility and construct the final regimens. Some CCs for pDST need to be re-examined to avoid systematic false-susceptible results in low-level resistant isolates.

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Interspecies transmission of the blaOXA-48 gene from Klebsiella pneumoniae high-risk clone ST147 to different Escherichia coli clones in the gut microbiota [PublishAheadOfPrint]

OXA-48—producing K. pneumoniae (OXA-Kpn) have quickly spread in Spain and other European countries (1)....

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Efficacy of Tilorone Dihydrochloride against Ebola Virus Infection [PublishAheadOfPrint]

Tilorone dihydrochloride (tilorone) is a small-molecule, orally bioavailable drug that is used clinically as an antiviral outside of the US. A machine learning model trained on anti-Ebola virus (EBOV) screening data previously identified tilorone as a potent in vitro EBOV inhibitor, making it a candidate for the treatment of Ebola virus disease (EVD). In the present study, a series of in vitro ADMET (absorption, distribution, metabolism, excretion, toxicity) assays demonstrated the drug has excellent solubility, high Caco-2 permeability, was not a P-glycoprotein substrate and had no inhibitory activity against five human CYP450 enzymes (3A4, 2D6, 2C19, 2C9 and 1A2). Tilorone was shown to have 52% human plasma protein binding with excellent plasma stability and a mouse liver microsome half-life of 48 minutes. Dose range-finding studies in mice demonstrated a maximum tolerated single dose of 100 mg/kg. A pharmacokinetics study in mice at 2 and 10 mg/kg dose levels showed that the drug is rapidly absorbed, has dose-dependent increases in C_max and AUC values with a half-life of approximately 18 hours in both males and females, although the exposure was ~2.5-fold higher in male mice. Tilorone doses of 25 and 50 mg/kg proved efficacious in protecting 90% of mice from a lethal challenge with mouse-adapted EBOV (maEBOV) with once daily intraperitoneal (ip) dosing for 8 days. A subsequent study showed that 30 mg/kg/day of tilorone given ip starting 2 or 24 hours post-challenge and continuing through Day 7 post infection was fully protective, indicating promising activity for the treatment of EVD.

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Discovery of new inhibitors of Toxoplasma gondii thanks to the Pathogen Box [PublishAheadOfPrint]

Toxoplasma gondii is a cosmopolitan protozoan parasite which affects approximately 30% of the population worldwide. The drugs currently used against toxoplasmosis are few in number and show several limitations, such as a drug intolerance, poor bioavailability or drug resistance mechanism developed by the parasite. Thus it is important to find new compounds able to inhibit parasite invasion or proliferation. In this study, the 400 compounds of the open access Pathogen Box provided by the Medicines for Malaria Venture (MMV) foundation were screened for their anti-Toxoplasma gondii activity. A preliminary in vitro screening performed over 72 hours by an enzyme-linked immunosorbent assay (ELISA) revealed fifteen interesting compounds that were effective against T. gondii at 1 μM. Their cytotoxicity was estimated on Vero cells and their 50% inhibitory concentration (IC₅₀) values were further calculated. As a result, eight anti-Toxoplasma gondii compounds with an IC₅₀ value lesser than 2 μM and a selectivity index (SI) value greater than 4 were identified. The most active was MMV675968, showing an IC₅₀ of 0.02 μM and a selectivity index value equal to 275. Two other compounds, MMV689480 and MMV687807, also showed a good activity against T. gondii with IC₅₀ values of 0.10 μM (SI = 86.6) and 0.15 μM (SI = 11.3), respectively. Structure-activity relationships for the eight selected compounds were also discussed on the basis of fingerprinting similarity measurements using the Tanimoto method. The anti-Toxoplasma gondii compounds highlighted here represent potential candidates for the development of new drugs that could be used against toxoplasmosis.

http://ift.tt/2zFZPDk

How to suction pancreatic juice from the duodenum: Endoscope, catheter, or cap-assisted?

Pancreatic cancer is associated with a very poor prognosis. The American Cancer Society estimates that in 2017, about 53,670 people will receive a diagnosis of pancreatic cancer and about 43,090 people will die of the disease. It is predicted that pancreatic cancer will be the second leading cause of cancer death in the United States by 2030.1 Although the 5-year relative survival is as low as 8% for all stages, the 5-year relative survival for localized tumor is 29%.2 Therefore, surgical resection of the tumor at an early stage is the only cure.

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ERCP: Time to take the lead off?

Multiple studies have shown ERCP to generate significant doses of ionizing radiation. Yet, with the exception of the pregnant patient, most endoscopists performing ERCP are not precisely aware of, much less concerned about, the ionizing radiation generated. It's just another day in the ERCP suite, and what counts is the procedural outcome: Was cannulation of the targeted duct accomplished, and was the therapeutic intervention successfully executed? Historically, the radiation exposure from ERCP to the patient has been perceived as trivial and—even when longer fluoroscopy times are needed—as a necessary tradeoff to reap the advantages of ERCP over more invasive and risky radiologic and surgical alternatives.

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Response:

We thank Dr Cotton1 for his insightful comments on the recent American Society for Gastrointestinal Endoscopy (ASGE) guideline document on privileging and credentialing in GI endoscopy as it pertains to competence in ERCP.2 The first issue raised in this letter relates to the number of the ERCPs that a trainee must complete before competency can be assessed and the lack of data on this subject in the published literature. We would like to clarify that the intent of this statement was to ensure that trainees complete at least 200 supervised independent ERCP procedures.

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Response:

We appreciate the thoughtful comments of Dr Agrawal1 regarding the Multi-Society Task Force (MSTF) recommendations on colorectal cancer screening.2 Dr Agrawal suggests that the MSTF should advise patients to ask prospective colonoscopists for their rate of adequate preparations. Dr Agrawal cites the ≥85% target for adequate preparations, which he attributes to the American College of Gastroenterology (ACG). This target, although endorsed by the ACG, was first presented by the MSTF.3 Thus, we strongly agree that colonoscopists should measure rates of adequate bowel preparation (defined by the use of bowel preparation descriptors or scores consistent with adequacy plus adherence to screening or surveillance recommendations appropriate to the examination findings) and make changes when needed to exceed this target.

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Zeroing in on endoscopic and histologic mucosal healing to reduce the risk of colorectal neoplasia in inflammatory bowel disease

The past 2 decades have witnessed unprecedented advances in our understanding of the causes and pathogenesis of inflammatory bowel disease (IBD). Taken together with an expanding therapeutic armamentarium, this has emboldened the definitions of disease control, placing greater emphasis on achieving mucosal healing than on clinical remission alone. What can now be achieved through abrogation of immunoinflammatory events such as reduction in disease relapse, hospitalization, surgery, and colorectal neoplasia (CRN) has redefined our perceptions of meaningful disease control.

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Information for readers

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Editors

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Continuing Medical Education Exam: December 2017

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Contents

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Choledocholithiasis: Should EUS replace MRCP in patients at intermediate risk?

Choledocholithiasis is a common adverse event of gallstones, occurring in 10% to 20% of patients undergoing cholecystectomy.1 Although ERCP is considered the criterion standard for diagnosis and management of choledocholithiasis, the diagnostic role of this modality is limited by its invasive nature and risk for adverse events such as post-ERCP pancreatitis (PEP).2 Pancreatitis is the most common adverse event of ERCP and is estimated to be responsible for 150 million dollars of health care expenditures annually in the United States.

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ASGE update

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Pancreatic function testing for the early diagnosis of chronic pancreatitis

Chronic pancreatitis is a syndrome.1 Not all disease syndromes have a single specific diagnostic test that corroborates the diagnosis but instead rely on a combination of clinical, laboratory, imaging, and pathologic characteristics in various combinations to define the disease (eg, systemic lupus erythematosus). Chronic pancreatitis occurs in patients with genetic, environmental, and other risk factors; has a diversity of mechanisms; and is associated with a wide variety of clinical features. In the past, chronic pancreatitis was defined only by the presence of specific morphologic changes (imaging features such as pancreatic calcification, or histologic characteristics demonstrating fibrosis) or by functional changes (gland failure with pancreatic exocrine or endocrine insufficiency).

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In upcoming issues...

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Covered bridge over troubled strictures

In this current issue of Gastrointestinal Endoscopy, Tal et al1 compare 2 different approaches for the treatment of anastomotic biliary strictures (ABSs) after orthotopic liver transplantation (OLT). The authors report the results of their prospective open-label 2-arm study comparing multiple plastic stents (MPSs) with covered self-expandable metal stents (cSEMSs). On the basis of these results, patients who undergo cSEMS placement for ABSs require fewer ERCP interventions (median ERCP sessions, 2; range, 2-12) than do patients undergoing MPS placement (median ERCP sessions, 4; range, 3-12; P < .001).

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Covered self-expanding metal stents: a promising therapy for difficult stone disease

We read with great interest the article by Hartery et al1 entitled "Covered self-expanding metal stents for the management of common bile duct stones." This retrospective study evaluated the safety and efficacy of inserting covered self-expanding metal stents (CSEMSs) alongside "difficult" stones in 44 patients at 2 tertiary referral centers. After the work by Cerefice et al2 in 2011, this is the second case series in the literature that has evaluated this modality in treating difficult stones after failed endoscopic extraction.

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Inadequate bowel preparation rates should be considered before screening colonoscopy is recommended

Rex et al1 provided a comprehensive update of the U.S. Multi-Society Task Force of Colorectal Cancer recommendations on colon cancer screening. They cite good evidence in support of a sequential approach based on colonoscopy, first based on sensitivity and cost effectiveness. The authors also discuss tools for patients (and primary care physicians) to judge whether colonoscopy is performed at a high level. These include asking about adenoma detection rate, cecal intubation rate, and use of split-dosing bowel preparation.

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ASGE guidelines for ERCP competence

I applaud the continuing efforts of the American Society for Gastrointestinal Endoscopy (ASGE) to improve the quality of endoscopy in the United States, and thus I read the latest comprehensive guidelines with interest.1 The section on ERCP has 2 surprising conclusions.

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Basket Study Yields Approval for Rare Blood Cancer [News in Brief]

Histology-independent trial leads to label expansion for vemurafenib.

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Beneficial Effects of Two Types of Personal Health Record Services Connected With Electronic Medical Records Within the Hospital Setting

Healthcare consumers must be able to make decisions based on accurate health information. To assist with this, we designed and developed an integrated system connected with electronic medical records in hospitals to ensure delivery of accurate health information. The system—called the Consumer-centered Open Personal Health Record platform—is composed of two services: a portal for users with any disease and a mobile application for users with cleft lip/palate. To assess the benefits of these services, we used a quasi-experimental, pretest-posttest design, assigning participants to the portal (n = 50) and application (n = 52) groups. Both groups showed significantly increased knowledge, both objective (actual knowledge of health information) and subjective (perceived knowledge of health information), after the intervention. Furthermore, while both groups showed higher information needs satisfaction after the intervention, the application group was significantly more satisfied. Knowledge changes were more affected by participant characteristics in the application group. Our results may be due to the application's provision of specific disease information and a personalized treatment plan based on the participant and other users' data. We recommend that services connected with electronic medical records target specific diseases to provide personalized health management to patients in a hospital setting.

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Patient-Perceived Facilitators of and Barriers to Electronic Portal Use: A Systematic Review

This systematic review describes characteristics of portal users and their perceptions of this emerging technology. Recent empirical evidence (2010-2016) was reviewed to answer three questions: (1) What are the characteristics of electronic patient portal users? (2) What are patient-perceived facilitators of electronic patient portal use? (3) What are patient-perceived barriers to electronic patient portal use? Characteristics of portal users are described according to three broad categories: demographic characteristics, patterns of use, and complexity and duration of disease. Three themes were found related to patient-perceived facilitators of use: provider encouragement, access/control over health information, and enhanced communication; two themes were found related to patient-perceived barriers to use: lack of awareness/training and privacy and security concerns. Understanding a patient's perception of technology is paramount in optimizing use. These insights will allow for development of better products and clinical processes that facilitate broad goals of improved use of information technology. Policy and practice implications are discussed, as well as suggestions for future research.

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Nurses’ Perception of Challenges in the Use of an Electronic Nursing Documentation System

This qualitative study was based on the Technology Acceptance Model and conducted through directed content analysis to explore perceptions of nurses in Iran of the challenges of using an electronic documentation system. Participants were selected through purposive sampling via interview from a teaching hospital in western Iran. Data were analyzed using MAXQDA 10. Data consistency was ensured through validation methods and by the researcher's prolonged engagement in the subject. Twelve codes, four subcategories, and two main categories ("perceived usefulness" and "perceived difficulty") emerged from the analysis of the data based on the Technology Acceptance Model. "Perceived usefulness" consisted of the subcategories "subjective norms" and "experienced benefits"; and "perceived difficulty" contained the subcategories "rationalization" as well as "challenges in accepting change." According to the Technology Acceptance Model, to promote acceptance of this system, the benefits of usage should be highlighted. The biggest hurdle to acceptance is familiarity and comfort with previous methods.

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Infusion Pump Interoperability: High Reliability and Safety Concerns Lead to Unintended Consequences

No abstract available

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Design and Implementation of the Intensive Care Unit Quality Management Registry: Monitoring Quality and Cost of an Adult Intensive Care Unit in a Greek State Hospital

Intensive care electronic registries have been instrumental in quality measurement, improvement, and assurance of intensive care. In this article, the development and pilot implementation of the Intensive Care Unit Quality Management Registry are described, with a particular focus on monitoring the quality and operational cost in an adult ICU at a northern Greek state hospital. A relational database was developed for a hospital ICU so that qualitative and financial data are recorded for further analysis needed for planning quality care improvement and enhanced efficiency. Key features of this database registry were low development cost, user friendliness, maximum data security, and interoperability in existing hospital information systems. The database included patient demographics, nursing and medical parameters, and quality and performance indicators as established in many national registries worldwide. Cost recording was based on a mixed approach: at patient level ("bottom-up" method) and at department level ("top-down" method). During the pilot phase of the database operation, regular monitoring of quality and cost data revealed several fields of quality excellence, while indicating room for improvement for others. Parallel recording and trending of multiple parameters showed that the database can be utilized for optimum ICU quality and cost management and also for further research purposes by nurses, physicians, and administrators.

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User-Centered Design, Experience, and Usability of an Electronic Consent User Interface to Facilitate Informed Decision-Making in an HIV Clinic

Health information exchange is the electronic accessibility and transferability of patient medical records across various healthcare settings and providers. In some states, patients have to formally give consent to allow their medical records to be electronically shared. The purpose of this study was to apply a novel user-centered, multistep, multiframework approach to design and test an electronic consent user interface, so patients with HIV can make more informed decisions about electronically sharing their health information. This study consisted of two steps. Step 1 was a cross-sectional, descriptive, qualitative study that used user-centric design interviews to create the user interface. This informed Step 2. Step 2 consisted of a one group posttest to examine perceptions of usefulness, ease of use, preference, and comprehension of a health information exchange electronic consent user interface. More than half of the study population had college experience, but challenges remained with overall comprehension regarding consent. The user interface was not independently successful, suggesting that in addition to an electronic consent user interface, human interaction may also be necessary to address the complexities associated with consenting to electronically share health information. Comprehension is key factor in the ability to make informed decisions.

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Text Messaging and Teen Sexual Health Behavior: Long-term Follow-up of a Cluster Randomized Trial

No abstract available

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Development of a Smartphone Application to Monitor Pediatric Patient-Reported Outcomes

Patient-reported outcomes are increasingly emphasized in clinical trials and population health studies. Our research team developed a smartphone app to track patient-reported outcomes of children with chronic diseases. The purpose of this study is to develop a patient-reported outcome reporting app and evaluate its usability. A multidisciplinary research team including health services researchers, pediatric nurses, and software engineers worked collaboratively in developing the patient-reported outcome app and administration portal. Group discussions and several rounds of feedback and modification were used. Ten pediatric patients with cancer, five parents, and two nurses participated in the usability study. We conducted content analyses in app development and usability evaluation. The app collected demographic information and patient-reported outcomes. Patient-reported outcomes were collected by Chinese versions of pediatric Patient-Reported Outcomes Measurement Information System Short Forms and Patient-Reported Outcomes Measurement Information System Parent Proxy Report Scales for Children. Pediatric patients aged 8 to 17 years and parents with a 5- to 7-year-old pediatric child used different age-appropriate questionnaires. The Web-based administration portal helped to manage demographic information, questionnaires, administrators, and survey-conducting organizations. The users liked the app. All participants felt that this app was easy to use and the interfaces were friendly to children. Nurses thought the administration portal interfaces were simple and the data were convenient to download for further analysis. We conclude that the app and its administration portal meet researchers and clinical nurses' demand and have potential to promote patient-reported outcomes in assessing quality of life and symptoms of pediatric patients.

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Patient-Perceived Facilitators of and Barriers to Electronic Portal Use: A Systematic Review

No abstract available

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Protective effect of garlic ( Allium sativum ) against zinc poisoning in the testicular tissue of goldfish ( Carassius auratus )

Abstract

Zinc is essential to the body; however, in high concentrations, it can be toxic. In this study, the protective effect of garlic (Allium sativum) against the toxic effect of zinc on the testicular tissues of goldfish (Carassius auratus) was assessed. Seventy-five healthy fish were allocated into 5 equal groups: control group, untreated; group 1, exposed to zinc sulfate (Merck, Germany) at dose of 3 mg/L; groups 2, 3, and 4 were also exposed to zinc sulfate in the same concentration as group 1 but their diet was supplemented with garlic (A. sativum) at 0.5, 1, and 2.5% of daily diet, respectively. After 45 days, 8 fish from each group were randomly selected, testicular tissue taken, and assessed histologically. Severe histopathologic lesions were seen in groups 1 and 2 and to lesser extents in groups 3 and 4 as garlic concentration increased. This showed that goldfish testicular tissue is sensitive to zinc toxicity and that garlic can reduce zinc accumulation in tissues, indicating that antioxidant compounds from garlic might act as chelators for zinc, allowing its excretion from the body.

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Virulent gene profile and antimicrobial susceptibility pattern of Shiga toxin-producing Escherichia coli (STEC) from humans in Maiduguri, Borno State, North-Eastern Nigeria

Abstract

Prevalence and distribution of Shiga toxin-producing Escherichia coli (STEC) serogroups majorly linked with public health hazards in Maiduguri and the antimicrobial resistance pattern profile of the isolates were determined. Our results show that the prevalence of STEC isolated from human patients with gastroenteritis attending hospitals in Maiduguri was 1.2% of the 600 stool specimens examined. Two patients out of the seven STEC positive isolates had diarrhoea, and no significant statistical association (P < 0.05) was found between STEC positive samples and diarrheal disease. There was significant (P < 0.05) variation in the prevalence of STEC among the age groups. However, there were statistical differences (P < 0.05) between the detection rates of the four serogroups encountered. Five (71.4%) of the E. coli O157 strain showed resistance to at least one of the antimicrobials tested. The only STEC O157 isolate from humans showed resistance to gentamycin, ampicillin, streptomycin and cefotaxime. The results of the antimicrobial susceptibility study showed high resistance (71%) profile to the agents tested. However, all the seven isolates from humans were sensitive to ceftazidime, ceftriaxone and chloramphenicol. In conclusion, the study did not demonstrate significant influence of sex but it did document the presence of stx2 genes in 14.2% and stx1 in 85.7% of the isolates and other genes detected in this study were eae and ehlyA among the isolates. Therefore, ceftazidime, ceftriaxone and chloramphenicol may be drugs of choice for treating infections caused by STEC in Maiduguri.

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Author's Response

We thank Dr. Morgan and her colleagues for their comments; however, we believe that they have misinterpreted our manuscript at several key points. Firstly, our manuscript did not address whether "people with gastrointestinal cancer did not benefit from the admission to sub-acute rehabilitation," nor did we draw conclusions in relation to all patients with gastrointestinal (GI) cancer. Rather, we focused on progressive metastatic GI cancer patients who were discharged to subacute rehabilitation (SAR) following inpatient admission.

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The Landscape of Glucose-Lowering Therapy and Cardiovascular Outcomes: From Barren Land to Metropolis

The choice of glucose-lowering therapy (GLT) has expanded to include 11 different classes in addition to insulin. Since the 2008 Food and Drug Administration guidance for industry and mandate of demonstrating cardiovascular (CV) safety prior to any new drug approval, there were several trials primarily conducted to establish that goal. Some had neutral effects, while there were positively beneficial outcomes with more recent studies. Hospitalization for congestive heart failure has also been a heterogeneous finding among the different classes of GLT, with drug outcomes ranging from risky to beneficial. The current review selectively focuses on the evidence for CV outcomes for each class of GLT and summarizes the existing guidelines with regard to these drugs in heart disease. Moreover, it illustrates the dynamic status in the development of evidence. Finally, the review enables healthcare providers to formulate a plan for hypoglycemic therapy which will optimize CV health, in a patient-centered manner.

http://ift.tt/2jmWzqr

HMMBinder: DNA-Binding Protein Prediction Using HMM Profile Based Features

DNA-binding proteins often play important role in various processes within the cell. Over the last decade, a wide range of classification algorithms and feature extraction techniques have been used to solve this problem. In this paper, we propose a novel DNA-binding protein prediction method called HMMBinder. HMMBinder uses monogram and bigram features extracted from the HMM profiles of the protein sequences. To the best of our knowledge, this is the first application of HMM profile based features for the DNA-binding protein prediction problem. We applied Support Vector Machines (SVM) as a classification technique in HMMBinder. Our method was tested on standard benchmark datasets. We experimentally show that our method outperforms the state-of-the-art methods found in the literature.

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Development of a surgical trainer assessment questionnaire

Background

The assessment of surgical trainees has become well-established in practice; however, this is not yet the case for surgical trainers. The aim of this study was to develop a trainer assessment questionnaire (OxTrAQ) based on the 12 key trainer attributes identified by a previous systematic review, to then explore this questionnaire's potential domains and test its reliability.

Methods

The OxTrAQ was piloted at two surgical training centres in two surgical sub-specialities. At each centre, every trainee assessed every trainer while under their clinical supervision.

Results

Internal consistency (Cronbach's alpha) was calculated for this 12-item questionnaire as 0.958. Factor analysis revealed two domains which accounted for 77.997% of the variance; these were the general domain (nine items) and the independence domain (three items). Inter-observer reliability was shown by the intraclass correlation coefficients (ICCs) (average measures) for the overall OxTrAQ score, general domain score and independence domain score which were 0.951, 0.945 and 0.955 for centre 1 and 0.857, 0.819 and 0.883 for centre 2, respectively. Intra-observer reliability was shown by the ICCs (average measures) for the overall OxTrAQ score, general domain score and independence domain score which were 0.925, 0.913 and 0.940, respectively. Construct validity was demonstrated by a high correlation (Spearman rho = 0.886, P = 0.019) between trainer scores and the scores predicted by the trainers themselves.

Conclusions

The OxTrAQ is a simple trainer assessment questionnaire which has demonstrated both high inter- and intra-observer reliability.

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Current evidence for the use of N-acetylcysteine following liver resection

Background

N-acetylcysteine (NAC) has many uses in medicine; notable in the management of paracetamol toxicity, acute liver failure and liver surgery. The aim of this review was to critically appraise the published literature for the routine use of NAC in liver resection surgery.

Methods

An electronic search was performed of EBSCOhost (Medline and CINAHL database), PubMed and the Cochrane Library for the period 1990–2016. MeSH headings: 'acetyl-cysteine', 'liver resection' and 'hepatectomy' were used to identify all relevant articles published in English.

Results

Following the search criteria used, three articles were included. Two of these studies were randomized controlled trials. All the studies collated data on morbidity and mortality. All three studies did not show a significant difference in overall complications rates in patients that underwent hepatic resection that had NAC infusion compared with patients that did not. In one study, NAC administration was associated with a higher frequency of grade A post-hepatectomy liver failure. In another study, a significantly higher incidence of delirium was observed in the NAC group, which led to the trial to be terminated early.

Conclusion

The current published data do not support the routine use of NAC following liver resection.

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Carotid endarterectomy: the change in practice over 11 years in a stroke centre

Background

Recent research evidence has impacted the practice of carotid endarterectomy (CEA). We aim to characterize changes in the practice and outcome of CEA over time in a single large-volume stroke centre.

Methods

All patients who underwent CEA from 2004 to 2014 and carotid angioplasty and stenting (CAS) from 2003 to 2008 at an Australian metropolitan tertiary stroke centre hospital were included. Clinical data were analysed to identify time trends in choice of intervention, patient selection, preoperative imaging utilization, surgical timing and outcome.

Results

There were 510 CEAs performed during 2004–2014 and 95 CASs during 2003–2008. The proportion of patients undergoing CEA compared to CAS increased from 60% to 90% from 2004 to 2008 (P < 0.001). CAS patients were more likely to have cardiac co-morbidities. From 2004 to 2014, the proportion of CEA patients aged ≥80 years increased (P = 0.001) and the proportion of asymptomatic patients decreased (P = 0.003) over time. Median time from symptom onset to surgery decreased from 52 days (Q1: 25, Q3: 74) in 2004 to 8 days (Q1: 5, Q3: 37) in 2014 (P < 0.001). Use of preoperative ultrasonography decreased whilst CT angiography and the number of imaging modalities applied to each patient increased over time (P < 0.001). Overall, 5.9% of CEAs were complicated by death, stroke or acute myocardial infarction with no significant change over time.

Conclusion

The trends in CEA practice at our centre align with international trends and guidelines. This study provides a representative indicator of Australian hospital practice, and illustrates how evidence from research is translated into clinical care.

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Papillary Thyroid Cancer and Coexisting Autoimmune Thyroiditis

Horm Metab Res 2017; 49: 869-872
DOI: 10.1055/s-0043-120922

Histological findings often display an association between papillary thyroid carcinomas (PTC) and autoimmune thyroiditis (AIT) and so differ significantly from follicular thyroid carcinomas (FTC). The aim of this interdisciplinary, retrospective study was to evaluate the association of AIT in patients with PTC and FTC and a control group of benign nodular goiters. One hundred thyroidectomies with histologically confirmed differentiated thyroid carcinomas, 67 with PTC and 33 with FTC, were submitted for examination. The two control groups consisted of 60 patients with euthyroid nodular goiter, displaying no signs for malignancy (no surgery) and 100 patients (second control group) with surgery of a benign nodular goiter. Controls were collected to obtain data about the incidence of significantly increased TPOAbs in the first group and of lymphocytic infiltrates (LI) in the second group. High TPOAbs were found in 35% (23/67) of patients with PTC. LI were detected by histology in 48% (32/67) of PTC. Ten patients (10/32) of this group showed the clinical and histological manifestation of a classic AIT with diffuse dense LI as well as diffuse hypoechogeneity in ultrasonography. In 7/32 cases, the histological report described focal dense LI (fAIT) and in 15/32 cases scant scattered LI. AIT and fAIT, together 25% of all PTC (17/67), showed germinal centers and can therefore be characterized as chronic autoimmune thyroiditis. In this group, high TPOAb could be detected in 94% (16/17). Scan scattered LI without germinal centers (15/32) do not represent a fAIT, although TPOAb are high in 47% (7/15). The younger age group (<45 years) showed significantly more often high TPOAbs (p<0.023) in comparison with the age-group older than 60 years. In contrast to PTC, only 4/33 (12%) patients with FTC had high TPOAb levels. We conclude that in contrast to benign euthyroid goiters and to FTC, different degrees of LI are often associated with high TPOAb levels and seem to be significantly increased in PTC, particularly prominent in younger age. There is a high coincidence between LI and high TPOAb levels. In the presence of hypoechoic thyroid nodule, signs of thyroid autoimmunity such as the presence of high TPOAbs, lymphocytic infiltration in cytology, and/or characteristic ultrasonic features, are arguments that might favor the decision for surgery if a cytologically indeterminate thyroid nodule is found and focal autonomy is excluded by szintiscan.
[...]

© Georg Thieme Verlag KG Stuttgart · New York

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Thymus Growth and Fetal Immune Responses in Diabetic Pregnancies

Horm Metab Res 2017; 49: 892-898
DOI: 10.1055/s-0043-120671

Type 1 diabetes (T1D) during pregnancy possibly affects the development of the thymus and the maturation of the immune system in the offspring. The aim of the ImmunDiabRisk study was to investigate thymus growth and maternal and fetal immune responses in pregnancies with and without T1D. The thymus circumferences of the fetuses of pregnant women with T1D (n=49) and without diabetes (n=59) were measured using ultrasound around the 29th gestational week and standardized for gestational age. Simultaneously, the frequencies and total numbers of cell markers were analyzed by flow cytometry in maternal peripheral blood, and at birth in umbilical cord blood. The standardized circumference of the thymus was similar in fetuses of mothers with and without T1D (p=0.26). We observed higher numbers of FOXP3 Tregs, memory Tregs, erythrocytes, and lymphocytes in the cord blood from T1D pregnancies (p=0.01, p=0.002, p=0.002 and p=0.02, respectively). The frequencies of CD4+/CD8+ T cells correlated positively in maternal blood and umbilical cord blood of mother-child pairs, as did the levels of neutrophils (Spearman's correlation coefficient r=0.43, p=0.02 for CD4+/CD8+ cells; r=0.46, p=0.03 for neutrophils), while no significant correlations were observed between thymus circumference and any cell markers in the child. Parts of the prenatal immune system seem to develop differently in the offspring of mothers with and without T1D. The correlation of Tregs between maternal blood and cord blood may indicate a significant cross-talk between the maternal and fetal immune system.
[...]

© Georg Thieme Verlag KG Stuttgart · New York

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Professor Sotorios Raptis

Horm Metab Res 2017; 49: 899-899
DOI: 10.1055/s-0043-121469

© Georg Thieme Verlag KG Stuttgart · New York

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Familial Hyperparathyroidism – Disorders of Growth and Secretion in Hormone-Secretory Tissue

Horm Metab Res 2017; 49: 805-815
DOI: 10.1055/s-0043-120670

Six syndromes of familial hyperparathyroidism are compared: 1) Familial hypocalciuric hypercalcemia (FHH) expresses primary hyperparathyroidism (PHPT) beginning at birth with lifelong hypercalcemia. There is nonsuppressed PTH secretion from outwardly normal parathyroid glands. It reflects germline heterozygous mutation in CASR, GNA11, or AP2S1. 2) Neonatal severe primary hyperparathyroidism is severest of the six syndromes. It requires urgent total parathyroidectomy in infancy. It usually reflects biallelic inactivation of the CASR. 3) Multiple endocrine neoplasia type 1 (MEN1) is most frequently expressed as PHPT with asymmetric enlargement of 3–4 parathyroids. Benign or malignant tumors may occur among 30 other tissues. It is predisposed by germline inactivation of MEN1 or rarely by inactivation of a cyclin dependent kinase inhibitor, and then termed MEN4. 4) Multiple endocrine neoplasia type 2A from RET activating mutation rarely presents as familial hyperparathyroidism, because medullary thyroid cancer and pheochromocytoma are more prominent. 5) Hyperparathyroidism-jaw tumor syndrome (HPT-JT) has frequent PHPT and benign jaw tumors. Twenty percent develop parathyroid cancer. It is predisposed by inactivating mutation in CDC73. 6) Familial isolated hyperparathyroidism causes multiple parathyroid tumors. It can be an incomplete expression of FHH, MEN1, HPT-JT or even of relatives without a shared driver mutation. However, in 20% of families it reflects GCM2 activating mutation. Five of the PHPT syndromes reflect overgrowth of parathyroid tissue; in contrast, familial hypocalciuric hypercalcemia reflects dysregulation of PTH secretion with little or no parathyroid overgrowth. These differences underlie major differences in clinical expression.
[...]

© Georg Thieme Verlag KG Stuttgart · New York

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Can Screening and Confirmatory Testing in the Management of Patients with Primary Aldosteronism be Improved?

Horm Metab Res
DOI: 10.1055/s-0043-121468

Widespread application of the plasma aldosterone/renin ratio (ARR) as a screening test has led to the recognition that primary aldosteronism (PA) is the most common specifically treatable and potentially curable form of hypertension, accounting for 5–10% of patients. Maximal detection requires accurate diagnostic approaches and awareness and control of factors that confound results, including most antihypertensives, posture, time of day, dietary salt, and plasma potassium. Recent studies have revealed potential for false positives in patients on beta-adrenoceptor blockers, and, when direct renin concentration (but not plasma renin activity) is used to measure renin, in women during the luteal phase of the menstrual cycle or receiving estrogen-containing contraceptives or hormonal replacement therapy. In addition to verapamil slow release, hydralazine and prazosin, moxonidine has minimal effects on the ARR and can be used to control hypertension during work-up. Fludrocortisone suppression testing, while probably the most reliable means of definitively confirming or excluding PA, is time consuming and expensive, requiring a five day inpatient stay. A novel approach, upright (seated) saline infusion suppression testing (SST), has shown excellent reliability with much greater sensitivity than conventional recumbent SST in a recent pilot study, and requires only a day visit. Accurate measurement of aldosterone is essential for each step of PA workup: introduction of new, highly reliable high-throughput mass spectrometric methods into clinical practice has represented a major advance. In response to concerns raised about accuracy of renin assays, new mass spectrometric methods for measuring angiotensin II are currently being assessed in the clinical setting.
[...]

© Georg Thieme Verlag KG Stuttgart · New York

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Thyroid Dysfunction States and Incident Cardiovascular Events: The Tehran Thyroid Study

Horm Metab Res
DOI: 10.1055/s-0043-121031

The objective of the study was to investigate the relation of different thyroid function states with the incidence of cardiovascular disease (CVD)/coronary heart disease (CHD) among a Middle-Eastern population with a high incidence of CVD/CHD. A total of 3975 participants entered the study (43.6% men). According to their thyroid stimulating hormone (TSH) and free thyroxin (FT4) levels, the participants were categorized into 5 groups: euthyroid, subclinical hypothyroidism, overt hypothyroidism, subclinical hyperthyroidism, and overt hyperthyroidism. Multivariable Cox proportional hazard models were used to assess the relation of different thyroid function states with incident CVD/CHD, with euthyroid state as reference. The mean age (SD) of the participants was 46.5 (12.0) years. At baseline, no significant difference was observed in the frequency of prevalent CVD cases (n=201) between all groups. No significant interaction was found between prevalent CVD and different thyroid function states with outcomes, hence, we did not exclude participants with prevalent CVD from data analysis. A total of 400 CVD events (358 CHD cases) during a median follow-up of 11.2 years (inter-quartile range: 1.96) occurred. During the follow-up, even in the age and sex adjusted model, no association was observed between different states of thyroid dysfunction and incidence of CVD/CHD. The multivariable hazard ratios (95% CI) of subclinical hypothyroidism, hypothyroidism, subclinical hyperthyroidism, and hyperthyroidism for CVD events were 1.21 (0.77–1.88), 0.76 (0.33–1.69), 0.81 (0.46–1.41) and 1.48 (0.70–3.16), respectively. Both at baseline and during follow-up, no relation was observed between different states of thyroid function with prevalence and incidence of CVD/CHD.
[...]

© Georg Thieme Verlag KG Stuttgart · New York

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Metabolic Endotoxemia-Activated Macrophages Promote Pancreatic β Cell Death via IFNβ-Xaf1 Pathway

Horm Metab Res
DOI: 10.1055/s-0043-121467

Metabolic endotoxemia has been implicated in the pathogenesis of type 2 diabetes. In addition to adipose tissue inflammation, inflammatory cell infiltration is also observed in islets, although its effect on islets is largely unknown. We hypothesized that macrophage infiltration into islets leads to impairment of α or β cell function, which ultimately act to exacerbate the pathophysiology of diabetes. Gene expression in a murine α cell line, αTC1, and β cell line, βTC6, was investigated by DNA microarray after co-culturing the cells with a murine macrophage cell line, RAW 264.7, in the presence or absence of bacterial endotoxin. Among the genes showing highly upregulated expression, genes specifically upregulated only in β cells were evaluated to determine the roles of the gene products on the cellular function of β cells. In both α and β cells, expression of type I interferon-responsive genes was highly upregulated upon endotoxin stimulation. Among these genes, expression of the X-linked inhibitor of apoptosis (Xiap)-associated factor 1 (Xaf1) gene, which is associated with the induction of apoptosis, was specifically enhanced in β cells by endotoxin stimulation. This upregulation appeared to be mediated by macrophage-derived interferon β (IFNβ), as endotoxin-stimulated macrophages produced higher amounts of IFNβ, and exogenous addition of IFNβ into βTC6 cultures resulted in increased Xaf1 protein production and cleaved caspase 3, which accelerated β-cell apoptosis. Macrophages activated by metabolic endotoxemia infiltrated into islets and produced IFNβ, which induced β-cell apoptosis by increasing the expression of Xaf1.
[...]

© Georg Thieme Verlag KG Stuttgart · New York

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Roles of Fibroblast Activation Protein and Hepatocyte Growth Factor Expressions in Angiogenesis and Metastasis of Gastric Cancer

Abstract

This study aims to explore the roles of fibroblast activation protein (FAP) and hepatocyte growth factor (HGF) expressions in the angiogenesis and metastasis of gastric cancer (GC). From May 2012 to December 2015, 110 GC patients who received surgical treatment in the First Hospital of Qinhuangdao were selected. The HGF and FAP expressions in 110 cases of GC, 130 cases of normal gastric mucosa and 115 cases of gastric ulcer were detected by streptavidin-perosidase (SP) method. Venous blood HGF level of GC patients was tested by enzyme-linked immunosorbent assay (ELISA). The micro-vessel number of the patients in the three groups were calculated and analyzed. In GC group, positive expression rates of FAP and HGF protein were 61.8% and 67.3% respectively, which were both higher than those in normal gastric mucosa and gastric ulcer groups. The micro-vessel numbers in patients of the normal gastric mucosa and gastric ulcer groups are far less than that in GC group. FAP, HGF and micro-vessel density (MVD) were significantly correlated with infiltration depth, tumor-node-metastasis (TNM) staging, lymph node metastasis (LNM) and distant metastasis. The results of ELISA showed that serum HGF level was related to tumor size, infiltration degree, TNM staging, LNM and distant metastasis. FAP and HGF expressions in GC were positively correlated with MVD, and the expressions of FAP and HGF in GC were in positive correlation. Our study provided evidence that high FAP and HGF expressions may be positively correlated with the angiogenesis and metastasis of GC.

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Automated quantification of steatosis: agreement with stereological point counting

Steatosis is routinely assessed histologically in clinical practice and research. Automated image analysis can reduce the effort of quantifying steatosis. Since reproducibility is essential for practical use, ...

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The effect of reducing EEG electrode number on the visual interpretation of the human expert for neonatal seizure detection

Optimising neuro-critical care in the newborn has become a high priority issue in paediatrics (Abend et al. 2011; Bonifacio et al. 2011; Glass et al. 2016). One of the key challenges in neuro-critical care is to provide brain monitoring that is continuous and uninterrupted in settings where personnel are changing constantly, neurophysiological support is limited, and an array of other medical devices are competing for cotside attention and placements. These practical considerations have led neonatologists to use a biparietal (P3-P4), or more recently, a two-channel (centro/fronto-parietal) derivation, to provide a measurement of neurological function (van Rooij et al.

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Be ready to respond with new certified safety kits, available from theEMSstore

COATESVILLE, Pa. — theEMSstore, a trusted, top supplier of critical supplies geared toward EMS professionals, is excited to now offer multi-purpose, easy-to-maintain and refill Certified Safety First Aid Kits. Accidents and injuries can happen at any moment, in any setting. For over 50 years, Certified Safety Mfg. has cultivated an uninterrupted record of excellence in bringing innovative first ...

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Intensive care antibiotic consumption and resistance patterns: a cross-correlation analysis

Over recent decades, a dramatic increase in infections caused by multidrug-resistant pathogens has been observed worldwide. The aim of the present study was to investigate the relationship between local resist...

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NeoAnalysis: a Python-based toolbox for quick electrophysiological data processing and analysis

In a typical electrophysiological experiment, especially one that includes studying animal behavior, the data collected normally contain spikes, local field potentials, behavioral responses and other associate...

http://ift.tt/2AGcdS1

Portable wireless neurofeedback system of EEG alpha rhythm enhances memory

Effect of neurofeedback training (NFT) on enhancement of cognitive function or amelioration of clinical symptoms is inconclusive. The trainability of brain rhythm using a neurofeedback system is uncertainty be...

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Outcomes of Dabigatran and Warfarin for Atrial Fibrillation in Contemporary Practice A Retrospective Cohort Study

Background:

Dabigatran (150 mg twice daily) has been associated with lower rates of stroke than warfarin in trials of atrial fibrillation, but large-scale evaluations in clinical practice are limited.

Objective:

To compare incidence of stroke, bleeding, and myocardial infarction in patients receiving dabigatran versus warfarin in practice.

Design:

Retrospective cohort.

Setting:

National U.S. Food and Drug Administration Sentinel network.

Patients:

Adults with atrial fibrillation initiating dabigatran or warfarin therapy between November 2010 and May 2014.

Measurements:

Ischemic stroke, intracranial hemorrhage, extracranial bleeding, and myocardial infarction identified from hospital claims among propensity score–matched patients starting treatment with dabigatran or warfarin.

Results:

Among 25 289 patients starting dabigatran therapy and 25 289 propensity score–matched patients starting warfarin therapy, those receiving dabigatran did not have significantly different rates of ischemic stroke (0.80 vs. 0.94 events per 100 person-years; hazard ratio [HR], 0.92 [95% CI, 0.65 to 1.28]) or extracranial hemorrhage (2.12 vs. 2.63 events per 100 person-years; HR, 0.89 [CI, 0.72 to 1.09]) but were less likely to have intracranial bleeding (0.39 vs. 0.77 events per 100 person-years; HR, 0.51 [CI, 0.33 to 0.79]) and more likely to have myocardial infarction (0.77 vs. 0.43 events per 100 person-years; HR, 1.88 [CI, 1.22 to 2.90]). However, the strength and significance of the association between dabigatran use and myocardial infarction varied in sensitivity analyses and by exposure definition (HR range, 1.13 [CI, 0.78 to 1.64] to 1.43 [CI, 0.99 to 2.08]). Older patients and those with kidney disease had higher gastrointestinal bleeding rates with dabigatran.

Limitation:

Inability to examine outcomes by dabigatran dose (unacceptable covariate balance between matched patients) or quality of warfarin anticoagulation (few patients receiving warfarin had available international normalized ratio values).

Conclusion:

In matched adults with atrial fibrillation treated in practice, the incidences of stroke and bleeding with dabigatran versus warfarin were consistent with those seen in trials. The possible relationship between dabigatran and myocardial infarction warrants further investigation.

Primary Funding Source:

U.S. Food and Drug Administration.

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