Massage for Children Undergoing Hematopoietic Cell Transplantation: A Qualitative Report

Background. No in-depth qualitative research exists about the effects of therapeutic massage with children hospitalized to undergo hematopoietic cell transplantation (HCT). The objective of this study is to describe parent caregivers' experience of the effects of massage/acupressure for their children undergoing HCT. Methods. We conducted a qualitative analysis of open-ended interviews with 15 parents of children in the intervention arm of a massage/acupressure trial. Children received both practitioner and parent-provided massage/acupressure. Results. Parents reported that their child experienced relief from pain and nausea, relaxation, and greater ease falling asleep. They also reported increased caregiver competence and closeness with their child as a result of learning and performing massage/acupressure. Parents supported a semistandardized massage protocol. Conclusion. Massage/acupressure may support symptom relief and promote relaxation and sleep among pediatric HCT patients if administered with attention to individual patients' needs and hospital routines and may relieve stress among parents, improve caregiver competence, and enhance the sense of connection between parent and child

Study protocol: a cluster randomized trial to evaluate the effectiveness and implementation of onsite GeneXpert testing at community health centers in Uganda (XPEL-TB).

BACKGROUND: Delays in diagnosis and treatment of tuberculosis (TB) remain common in high-burden countries. To improve case detection, substantial investments have been made to scale-up Xpert MTB/RIF (Xpert), a cartridge-based nucleic acid amplification test that can detect TB within 2 hours, as a replacement for sputum smear microscopy. However, the optimal strategy for implementation of Xpert testing remains unclear. METHODS: The Xpert Performance Evaluation for Linkage to Tuberculosis Care (XPEL-TB) trial uses an ultra-pragmatic, hybrid type II effectiveness-implementation design to assess the effectiveness and implementation of a streamlined strategy for delivery of Xpert testing in real-world settings. Twenty health centers with TB microscopy units were selected to participate in the trial, with ten health centers randomized to the intervention strategy (onsite molecular testing using GeneXpert Edge, process redesign to facilitate same-day TB diagnosis and treatment, and performance feedback) or routine care (onsite sputum smear microscopy plus referral of sputum samples to Xpert testing sites). The primary outcome is the number of patients with microbiologically confirmed TB who were initiated on treatment within 14 days of presentation to the health center, which reflects successful completion of the TB diagnostic evaluation process. Secondary outcomes include health outcomes (6-month vital status), as well as measures of the reach, adoption, and implementation of the intervention strategy. DISCUSSION: The design elements and implementation approach for the XPEL-TB trial were intentionally selected to minimize disruptions to routine care procedures, with the goal of limiting their influence on key primary and secondary outcomes. Trial findings may result in increased support and funding for rapid, onsite molecular testing as the standard-of-care for all patients being evaluated for TB. TRIAL REGISTRATION: US National Institutes of Health's ClinicalTrials.gov, NCT03044158. Registered 06 February 2017. Pan African Clinical Trials Registry, PACTR201610001763265. Registered 03 September 2016

Age and gender differences in narcissism: A comprehensive study across eight measures and over 250,000 participants

Age and gender differences in narcissism have been studied often. However, considering the rich history of narcissism research accompanied by its diverging conceptualizations, little is known about age and gender differences across various narcissism measures. The present study investigated age and gender differences and their interactions across eight widely used narcissism instruments (i.e., Narcissistic Personality Inventory, Hypersensitive Narcissism Scale, Dirty Dozen, Psychological Entitlement Scale, Narcissistic Personality Disorder Symptoms from the Diagnostic and Statistical Manual of Mental Disorders, Version IV, Narcissistic Admiration and Rivalry Questionnaire-Short Form, Single-Item Narcissism Scale, and brief version of the Pathological Narcissism Inventory). The findings of Study 1 (N = 5,736) revealed heterogeneity in how strongly the measures are correlated. Some instruments loaded clearly on one of the three factors proposed by previous research (i.e., Neuroticism, Extraversion, Antagonism), while others cross-loaded across factors and in distinct ways. Cross-sectional analyses using each measure and meta-analytic results across all measures (Study 2) with a total sample of 270,029 participants suggest consistent linear age effects (random effects meta-analytic effect of r = -.104), with narcissism being highest in young adulthood. Consistent gender differences also emerged (random effects meta-analytic effect was -.079), such that men scored higher in narcissism than women. Quadratic age effects and Age × Gender effects were generally very small and inconsistent. We conclude that despite the various conceptualizations of narcissism, age and gender differences are generalizable across the eight measures used in the present study. However, their size varied based on the instrument used. We discuss the sources of this heterogeneity and the potential mechanisms for age and gender differences

The state of the Martian climate

60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes

Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization.

The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD

Design and execution of a public randomization ceremony to enhance stakeholder engagement within a cluster randomized trial to improve tuberculosis diagnosis in Uganda.

Public randomization ceremonies have been proposed as a strategy to strengthen stakeholder engagement and address concerns and misconceptions associated with trial randomization. However, there are few published examples that describe how to conduct a public randomization ceremony with meaningful stakeholder engagement or how such ceremonies impact stakeholder perceptions about randomization and the randomization process. Cluster randomization for the GeneXpert Performance Evaluation for Linkage to Tuberculosis Care (XPEL-TB) trial was conducted at a public randomization ceremony attended by 70 stakeholders in Kampala, Uganda. Presentations given by the Acting Assistant Commissioner from the Uganda National Tuberculosis and Leprosy Programme and trial investigators emphasized how the trial aimed to further national TB goals, as well as how stakeholders contributed to the intervention design. The purpose and process of randomization were described using simple text and visuals. Randomization was an interactive activity that required participation of stakeholders from each trial site. A survey administered to stakeholders at the end of the ceremony suggested high comprehension of randomization (98%), trust in the randomization process (96%), and satisfaction with randomization outcomes (96%). Public randomization ceremonies should be considered more routinely to engage stakeholders in and address potential concerns about the fairness and impartiality of the randomization process for community-based trials

Future perspectives in melanoma research: meeting report from the "Melanoma Bridge";: Napoli, December 3rd-6th 2014.

The fourth "Melanoma Bridge Meeting" took place in Naples, December 3-6th, 2014. The four topics discussed at this meeting were: Molecular and Immunological Advances, Combination Therapies, News in Immunotherapy, and Tumor Microenvironment and Biomarkers. Until recently systemic therapy for metastatic melanoma patients was ineffective, but recent advances in tumor biology and immunology have led to the development of new targeted and immunotherapeutic agents that prolong progression-free survival (PFS) and overall survival (OS). New therapies, such as mitogen-activated protein kinase (MAPK) pathway inhibitors as well as other signaling pathway inhibitors, are being tested in patients with metastatic melanoma either as monotherapy or in combination, and all have yielded promising results. These include inhibitors of receptor tyrosine kinases (BRAF, MEK, and VEGFR), the phosphatidylinositol 3 kinase (PI3K) pathway [PI3K, AKT, mammalian target of rapamycin (mTOR)], activators of apoptotic pathway, and the cell cycle inhibitors (CDK4/6). Various locoregional interventions including radiotherapy and surgery are still valid approaches in treatment of advanced melanoma that can be integrated with novel therapies. Intrinsic, adaptive and acquired resistance occur with targeted therapy such as BRAF inhibitors, where most responses are short-lived. Given that the reactivation of the MAPK pathway through several distinct mechanisms is responsible for the majority of acquired resistance, it is logical to combine BRAF inhibitors with inhibitors of targets downstream in the MAPK pathway. For example, combination of BRAF/MEK inhibitors (e.g., dabrafenib/trametinib) have been demonstrated to improve survival compared to monotherapy. Application of novel technologies such sequencing have proven useful as a tool for identification of MAPK pathway-alternative resistance mechanism and designing other combinatorial therapies such as those between BRAF and AKT inhibitors. Improved survival rates have also been observed with immune-targeted therapy for patients with metastatic melanoma. Immune-modulating antibodies came to the forefront with anti-CTLA-4, programmed cell death-1 (PD-1) and PD-1 ligand 1 (PD-L1) pathway blocking antibodies that result in durable responses in a subset of melanoma patients. Agents targeting other immune inhibitory (e.g., Tim-3) or immune stimulating (e.g., CD137) receptors and other approaches such as adoptive cell transfer demonstrate clinical benefit in patients with melanoma as well. These agents are being studied in combination with targeted therapies in attempt to produce longer-term responses than those more typically seen with targeted therapy. Other combinations with cytotoxic chemotherapy and inhibitors of angiogenesis are changing the evolving landscape of therapeutic options and are being evaluated to prevent or delay resistance and to further improve survival rates for this patient population. This meeting's specific focus was on advances in combination of targeted therapy and immunotherapy. Both combination targeted therapy approaches and different immunotherapies were discussed. Similarly to the previous meetings, the importance of biomarkers for clinical application as markers for diagnosis, prognosis and prediction of treatment response was an integral part of the meeting. The overall emphasis on biomarkers supports novel concepts toward integrating biomarkers into contemporary clinical management of patients with melanoma across the entire spectrum of disease stage. Translation of the knowledge gained from the biology of tumor microenvironment across different tumors represents a bridge to impact on prognosis and response to therapy in melanoma