Evaluation of the Olweus Bullying Prevention Program in US Urban Middle Schools Using a Multiple Baseline Experimental Design.

We evaluated the impact of the Olweus Bullying Prevention Program (OBPP) in an 8-year study in urban middle schools that served primarily African American students living in low-income areas. Participants included 2755 students and 242 teachers. We evaluated the OBPP with a multiple-baseline experimental design where the order and intervention start time was randomly assigned for each school. We assessed the frequency of bullying behaviors and experiences including physical, relational, and verbal aggression and victimization using teacher ratings of student behavior and student-reported data, as well as cyber aggression and victimization and school climate measures using student-reported data. For teacher ratings of student behavior, we found significant main effects across all subtypes of aggression and victimization, with some variability in the timing of effects. The pattern of findings showed delayed intervention effects for boys and a weaker impact of the OBPP on 6th graders. We found main effects for student-reported cyber aggression and victimization, relational aggression, and a composite of physical, verbal, and relational victimization. Decreases in victimization emerged in the 1st or 2nd year of intervention, and reductions in aggression emerged during the 3rd year. Across all findings, once intervention effects emerged, they remained significant in subsequent intervention years. The OBPP resulted in significant decreases in student- and teacher-reported aggression and victimization. However, this intervention had limited impact on general areas of school climate including teacher support, positive peer interactions, and school safety. Overall, the findings offer important prevention and research implications.

A school-based expressive writing intervention for at-risk urban adolescents' aggressive behavior and emotional lability.

This school-based randomized controlled trial tested the efficacy of 2 expressive writing interventions among youth living in high-violence urban neighborhoods. Seventeen classrooms (n = 258 seventh graders; 55% female; 91% African American/Black) from 3 public schools were randomized to 3 conditions in which they wrote 8 times about a nonemotional topic (control condition) or about experiencing and witnessing violence following either a standard or an enhanced expressive writing protocol. Outcomes were assessed 1 month prior and 2 and 6 months postintervention and included teacher-rated emotional lability and aggressive behavior and child-rated physical aggression. Intent-to-treat, mixed-model analyses controlled for preintervention measures of outcomes, sex, race, and family structure. At 2 months postintervention, relative to controls, students in the standard expressive writing condition had lower levels of teacher-rated aggression and lability (d = -.48). The beneficial effects of the writing interventions on aggression and lability were stronger at higher levels of community violence exposure.

Knowledge Management as a Pharmaceutical Quality System Enabler: How Enhanced Knowledge Transfer Can Help Close the ICH Q10 to ICH Q12 Gap.

Knowledge management (KM) is identified in ICH Q10 (Pharmaceutical Quality System), as a key enabler to the pharmaceutical quality system (PQS). ICH Q8 (Pharmaceutical Development), ICH Q11 (Development and Manufacture of Drug Substances), and ICH Q12 (Technical and Regulatory Considerations for Pharmaceutical Product Lifecycle Management) each build on the expectation that knowledge will be managed effectively in order to support and improve the product and process across the pharmaceutical product life cycle. However, in spite of the fact that KM was introduced in ICH Q10 over 10 years ago, there is ample evidence that it is not yet a mature discipline within the biopharmaceutical sector, and the authors suggest that this could hinder full realization of the potential benefits of ICH Q8, ICH Q11, and ICH Q12. The Pharmaceutical Regulatory Science Team (PRST), a research team based at the Dublin Technological University (TU Dublin) in Ireland, has been conducting research on KM for several years, and this paper presents the next phase in this research. Specifically, the focus of this current research was to explore ways to offer practical solutions to improve the management of knowledge across the pharmaceutical product life cycle, starting with a focus on enhancing knowledge transfer during technology transfer projects. The typical challenges associated with ineffective knowledge transfer were presented and the high-level requirements needed to address these were identified through the research. From these requirements, a four-step framework was developed as a systematic means to enhance knowledge transfer. Accompanying the framework was a KM toolkit consisting of a range of KM practices (tools, processes, and behaviors) to facilitate more effective knowledge flow during technology transfer. It was then illustrated how such a framework can be extended across the entire pharmaceutical product life cycle, supporting the advancement of KM from an enabler in ICH Q10 to a key consideration (both technical and regulatory) in ICH Q12.

On the possibility of a disabled life in capitalist ruins: Black workers with sickle cell disorder in England.

The link between workers with sickle cell disorder (SCD) and employment has until now been seen through the lens of the person's disease, not their relationship to work (paid and unpaid). Using SCD as a case study, we foreground relations of employment, setting sickle cell and work into ecological context. In 2018, two focus group discussions and 47 depth-interviews were conducted with black disabled workers living with SCD across England. The relational concepts of Anna Tsing (2015) - salvage accumulation, entanglement and precarity - were used as an analytical framework to assess the reported experiences. To understand the experiences of those with SCD and employment, it is necessary to apprehend the whole ecology of their bonds to their bodies; their social relationships of kin and family; and their wider social relations to communities. Paid employment breaks bonds crucial to those living with SCD. First, employers can only extract sufficient productive value from workers if they disregard the necessary self-care of a precarious body. Secondly, reproducing labour though child-care, housework and care work is a taken-for-granted salvage central to capitalism. Thirdly, voluntary and community work are salvaged for free by employers towards their accumulation of profits. People with SCD find bond-making activities that create the commons life-affirming, thereby reconfiguring our understanding of connections between disability and work. Tsing, AL (2015) The Mushroom at the End of the World: On the Possibility of Life in Capitalist Ruins Princeton, NJ: Princeton University Press.

Quality Risk Management-A Role-Based Competency Model.

In collaboration with the Pharmaceutical Regulatory Science Team (PRST), a research team based at the Technological University Dublin (TU Dublin) in Ireland, a research study exploring the need for developing quality risk management (QRM) role-based competencies as fundamental elements to realizing QRM's benefits was conducted. The research study followed a hybrid Delphi research methodology of which elements are presented in the paper titled "Quality Risk Management Competency Model-Case for the need for QRM Competencies." This paper presents the second part of the Delphi research methodology, focusing on the results of a detailed technical and behavioral competencies questionnaire and a proposed QRM role-based competency model.

Quality Risk Management Competency Model-Case for the Need for QRM Competencies.

The Pharmaceutical Regulatory Science Team (PRST), a research team based at the Dublin Technological University (TU Dublin) in Ireland, recently conducted a Quality Risk Management (QRM) survey and a face-to-face focus group workshop to assess the level of formality of QRM roles in the biopharmaceutical sector. This was carried out as part of a research study, which identified the need for the development of QRM role-based competencies as fundamental to realizing QRM's benefits. The research study followed a hybrid Delphi research methodology composed of: (1) Survey 1, (2) focus group workshop, (3) Survey 2, and (4) competency model development. This paper presents the results of Survey 1 and the focus group workshop. Survey 1 explored the need for QRM role-based competencies and the subsequent face-to-face focus group workshop built on this to propose initial standard QRM roles, with a view to confirming these and developing associated competencies. This paper presents the findings from Survey 1 and the focus group workshop. The results of the follow-up research activities will be presented in a subsequent paper.LAY ABSTRACT: The publication of the ICH Q9 Quality Risk Management (QRM) guideline in 2005 has greatly impacted the biopharmaceutical sector. Fourteen years after Q9, the benefits of QRM are yet to be realized. The biopharmaceutical sector still struggles with the implementation of Q9 principles to effectively assess and manage product quality risks as a surrogate for patient safety.This paper looks at the need for standard QRM roles and the associated competencies for those roles.

Quality Risk Management - A Role-Based Competency Model.

In collaboration with the Pharmaceutical Regulatory Science Team (PRST), a research team based at the Technological University Dublin (TU Dublin) in Ireland, a research study exploring the need for developing QRM role-based competencies, as fundamental elements to realizing Quality Risk Management 's benefits was conducted. The research study followed a hybrid Delphi research methodology of which elements are presented in paper titled ″Quality Risk Management Competency Model- Case for the need for QRM Competencies.″ This paper presents the second part of the Delphi research methodology, focusing on the results of a detailed technical and behavioral competencies questionnaire and a proposed QRM role-based competency model.

Familial hypertrophic cardiomyopathy-linked mutant troponin T causes stress-induced ventricular tachycardia and Ca2+-dependent action potential remodeling.

The cardiac troponin T (TnT) I79N mutation has been linked to familial hypertrophic cardiomyopathy and high incidence of sudden death, despite causing little or no cardiac hypertrophy in patients. Transgenic mice expressing mutant human TnT (I79N-Tg) have increased cardiac contractility, but no ventricular hypertrophy or fibrosis. Enhanced cardiac function has been associated with myofilament Ca2+ sensitization, suggesting altered cellular Ca2+ handling. In the present study, we compare cellular Ca2+ transients and electrophysiological parameters of 64 I79N-Tg and 106 control mice in isolated myocytes, isolated perfused hearts, and whole animals. Ventricular action potentials (APs) measured in isolated I79N-Tg hearts and myocytes were significantly shortened only at 70% repolarization. No significant differences were found either in L-type Ca2+ or transient outward K+ currents, but inward rectifier K+ current (IK1) was significantly decreased. More critically, Ca2+ transients of field-stimulated ventricular I79N-Tg myocytes were reduced and had slow decay kinetics, consistent with increased Ca2+ sensitivity of I79N mutant fibers. AP differences were abolished when myocytes were dialyzed with Ca2+ buffers or after the Na+-Ca2+ exchanger was blocked by Li+. At higher pacing rates or in presence of isoproterenol, diastolic Ca2+ became significantly elevated in I79N-Tg compared with control myocytes. Ventricular ectopy could be induced by isoproterenol-challenge in isolated I79N-Tg hearts and anesthetized I79N-Tg mice. Freely moving I79N-Tg mice had a higher incidence of nonsustained ventricular tachycardia (VT) during mental stress (warm air jets). We conclude that the TnT-I79N mutation causes stress-induced VT even in absence of hypertrophy and/or fibrosis, arising possibly from the combination of AP remodeling related to altered Ca2+ transients and suppression of IK1.

Dealing with aggressive behavior within the health care team: a leadership challenge.

During an interdisciplinary Canadian leadership forum [ (click on the Conferences icon)], participants were challenged to develop an approach to a difficult leadership/management situation. In a scenario involving aggressive behavior among health care providers, participants identified that, before responding, an appropriate leader should collect additional information to identify the core problem(s) causing such behavior. Possibilities include stress; lack of clear roles, responsibilities, and standard operating procedures; and, finally, lack of training on important leadership/management skills. As a result of these core problems, several potential solutions are possible, all with potential obstacles to implementation. Additional education around communication and team interaction was felt to be a priority. In summary, clinical leaders probably have a great deal to gain from augmenting their leadership/management skills.

Massive pulmonary embolus without hypoxemia.

OBJECTIVE: To describe a patient who had been taking ibuprofen for 3 days before the diagnosis of a massive pulmonary embolus without hypoxemia. DESIGN: Institutional review board-approved case report. SETTING: Pediatric intensive care unit. PATIENT: A 16-yr-old male with a history of supraventricular tachycardia. RESULTS: The patient underwent an electrophysiology study and developed mild shortness of breath and then chest pain 2 and 4 days later, respectively. He took ibuprofen for 3 days. Evaluation 1 wk following the procedure revealed dyspnea and tachycardia. Arterial blood gas in room air was significant for hypocarbia without hypoxemia (Pao2, 108 mm Hg; Paco2, 28 mm Hg). Ventilation perfusion scan and computed axial tomography with intravenous contrast were consistent with a massive pulmonary embolus and left external iliac vein thrombus. He received anticoagulation, thrombolysis, a stent in the left iliac vein, and a filter in the inferior vena cava. Perfusion gradually improved and he was discharged home on oral anticoagulation. CONCLUSIONS: The absence of hypoxemia (including a normal alveolar-arterial oxygen difference) in our patient with a massive pulmonary embolus may have been related to cyclooxygenase inhibition due to ibuprofen, with improvement in ventilation-perfusion mismatch.

Enabling ICH Q10 Implementation--Part 1. Striving for Excellence by Embracing ICH Q8 and ICH Q9.

This article is the first in a series of articles that will focus on understanding the implementation essentials necessary to deliver operational excellence through a International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) Q10-based pharmaceutical quality system (PQS). The authors examine why, despite the fact that the ICH Q10 guideline has been with us since 2008, the transformation of the traditional Quality Management Systems QMS in use within the pharmaceutical industry is a work in progress for only a few forward-thinking organisations. Unfortunately, this transformation remains a mere aspiration for the majority of organisations. We explore the apparent lack of progress by the pharmaceutical sector in adopting six sigma and related quality management techniques to ensure the availability of high-quality medicines worldwide. The authors propose that the desired progress can be delivered through two key shifts in our current practices; by embodying the principles of operational excellence in every aspect of our business and by learning how to unlock the scientific and tacit knowledge within our organisations. LAY ABSTRACT: It has been ten years since The Wall Street Journal revealed the pharmaceutical industry's "little secret" comparing the perceived level of manufacturing expertise in the industry as lagging far behind those of potato-chip and laundry-soap makers. Would you consider the quality and manufacturing strategies in place today in your organisation to be more efficient and scientifically based than those of 2003? If so, what evidence exists for you to draw any conclusion regarding enhanced performance? Do your current practices drive innovation and facilitate continual improvement and if so, how? Ultimately, can you confidently affirm that patient-related risks associated with the product(s) manufactured by your organisation have been reduced due to the quality assurance program now applied within your organisation? This article asks you to question if you have truly embraced Q8(R2), Q9, and Q10, and in doing so can you demonstrate that you have made the necessary changes that would warrant reduced regulatory oversight?

Quality Risk Management: Putting GMP Controls First.

This paper presents a practical way in which current approaches to quality risk management (QRM) may be improved, such that they better support qualification, validation programs, and change control proposals at manufacturing sites. The paper is focused on the treatment of good manufacturing practice (GMP) controls during QRM exercises. It specifically addresses why it is important to evaluate and classify such controls in terms of how they affect the severity, probability of occurrence, and detection ratings that may be assigned to potential failure modes or negative events. It also presents a QRM process that is designed to directly link the outputs of risk assessments and risk control activities with qualification and validation protocols in the GMP environment. LAY ABSTRACT: This paper concerns the need for improvement in the use of risk-based principles and tools when working to ensure that the manufacturing processes used to produce medicines, and their related equipment, are appropriate. Manufacturing processes need to be validated (or proven) to demonstrate that they can produce a medicine of the required quality. The items of equipment used in such processes need to be qualified, in order to prove that they are fit for their intended use. Quality risk management (QRM) tools can be used to support such qualification and validation activities, but their use should be science-based and subject to as little subjectivity and uncertainty as possible. When changes are proposed to manufacturing processes, equipment, or related activities, they also need careful evaluation to ensure that any risks present are managed effectively. This paper presents a practical approach to how QRM may be improved so that it better supports qualification, validation programs, and change control proposals in a more scientific way. This improved approach is based on the treatment of what are called good manufacturing process (GMP) controls during those QRM exercises. A GMP control can be considered to be any control that is put in place to assure product quality and regulatory compliance. This improved approach is also based on how the detectability of risks is assessed. This is important because when producing medicines, it is not always good practice to place a high reliance upon detection-type controls in the absence of an adequate level of assurance in the manufacturing process that leads to the finished medicine.

Another form to fill in! Clients' reflections on the hospice use of questionnaires.

GOALS OF WORK: The use of validated tools is increasingly accepted as an unqualified good that is viewed as best practice in supportive care. This article begins to explore the impact of standardized questionnaire use in supportive care by presenting findings from recent qualitative research on clients' perceptions of the use of standardized assessment tools during their hospice experience. PATIENTS AND METHODS: There were two arms to this phenomenological descriptive study: A. Interviews with hospice patients and their carers; B. Interviews with hospice staff. The results from arm A are reported in this article. This involved interviews with ten families (available patient and carer) who had hospice experience with questionnaires and ten families who were cared for without questionnaires. The interviews were audiorecorded, transcribed verbatim, and thematically analysed. MAIN RESULTS: The research presented in this article is seminal work in the area which affirms significant concerns about the use of questionnaires in hospice practice. The evidence indicates the majority of clients dislike the use of questionnaires and points to questionnaire use being a practice built around staff, rather than client, needs. The findings also provide insight into the process of collusion by which hospice workers who are enthusiastic about the use of questionnaires can be led to believe, because of client gratitude, that the process is positive. CONCLUSIONS: Questionnaires should not be seen as an unqualified good, and thus should not be automatically accepted as best practice within hospice or palliative care service provision.

The electrophysiology of atrioventricular nodal reentry tachycardia following the Mustard or Senning procedure and its radiofrequency ablation.

We describe the electrophysiological studies undertaken in four patients with atrioventricular nodal reentry tachycardia in the setting of concordant atrioventricular and discordant ventriculo-arterial connections (transposition). Radiofrequency ablation was attempted in three, all with success. Clear evidence of dual antegrade pathways through the atrioventricular node was present in only one of the four, but other characteristics of discrete fast and slow pathways into the atrioventricular node were present in all. Atrioventricular nodal reentry tachycardia was inducible in all. In the three patients in whom ablation was attempted, the application of radiofrequency energy to the low medial regions of the systemic venous atrium (morphologically left) consistently caused junctional accelerated rhythm, but these lesions were not successful in eliminating the tachycardia. Successful radiofrequency ablation required a retrograde approach to the region of the slow pathway in the pulmonary venous atrium (morphologically right).

Transcutaneous implantation of an internal cardioverter defibrillator in a small infant with recurrent myocardial ischemia and cardiac arrest simulating sudden infant death syndrome.

This report describes the implantation of a transcutaneous ICD system using a small patch electrode in the subscapular position, and an active-can device in a 5.3-kg infant. The indication for ICD implantation was recurrent cardiac arrest in the presence of normal coronary anatomy. Metabolic evaluation suggested a defect in fatty acid oxidation.

Targeted point mutagenesis of mouse Kcnq1: phenotypic analysis of mice with point mutations that cause Romano-Ward syndrome in humans.

Inherited long QT syndrome is most frequently associated with mutations in KCNQ1, which encodes the primary subunit of a potassium channel. Patients with mutations in KCNQ1 may show only the cardiac defect (Romano-Ward syndrome or RWS) or may also have severe deafness (Jervell and Lange-Nielsen syndrome or JLNS). Targeted disruption of mouse Kcnq1 models JLNS in that mice are deaf and show abnormal ECGs. However, the phenotype is broader than that seen in patients. Most dramatically, the inner ear defects result in a severe hyperactivity/circling behavior, which may influence cardiac function. To understand the etiology of the cardiac phenotype in these mice and to generate a potentially more useful model system, we generated new mouse lines by introducing point mutations associated with RWS. The A340E line phenocopies RWS: the repolarization phenotype is inherited in a dominant manner and is observed independent of any inner ear defect. The T311I line phenocopies JLNS, with deafness associated with inner hair cell malfunction.