Rituximab in B-Cell Hematologic Malignancies: A Review of 20 Years of Clinical Experience

Rituximab is a human/murine, chimeric anti-CD20 monoclonal antibody with established efficacy, and a favorable and well-defined safety profile in patients with various CD20-expressing lymphoid malignancies, including indolent and aggressive forms of B-cell non-Hodgkin lymphoma. Since its first approval 20 years ago, intravenously administered rituximab has revolutionized the treatment of B-cell malignancies and has become a standard component of care for follicular lymphoma, diffuse large B-cell lymphoma, chronic lymphocytic leukemia, and mantle cell lymphoma. For all of these diseases, clinical trials have demonstrated that rituximab not only prolongs the time to disease progression but also extends overall survival. Efficacy benefits have also been shown in patients with marginal zone lymphoma and in more aggressive diseases such as Burkitt lymphoma. Although the proven clinical efficacy and success of rituximab has led to the development of other anti-CD20 monoclonal antibodies in recent years (e.g., obinutuzumab, ofatumumab, veltuzumab, and ocrelizumab), rituximab is likely to maintain a position within the therapeutic armamentarium because it is well established with a long history of successful clinical use. Furthermore, a subcutaneous formulation of the drug has been approved both in the EU and in the USA for the treatment of B-cell malignancies. Using the wealth of data published on rituximab during the last two decades, we review the preclinical development of rituximab and the clinical experience gained in the treatment of hematologic B-cell malignancies, with a focus on the well-established intravenous route of administration. This article is a companion paper to A. Davies, et al., which is also published in this issue

Uncovering Tacit Knowledge: A Pilot Study to Broaden the Concept of Knowledge in Knowledge Translation

BACKGROUND: All sectors in health care are being asked to focus on the knowledge-to-practice gap, or knowledge translation, to increase service effectiveness. A social interaction approach to knowledge translation assumes that research evidence becomes integrated with previously held knowledge, and practitioners build on and co-create knowledge through mutual interactions. Knowledge translation strategies for public health have not provided anticipated positive changes in evidence-based practice, possibly due in part to a narrow conceptualization of knowledge. More work is needed to understand the role of tacit knowledge in decision-making and practice. This pilot study examined how health practitioners applied tacit knowledge in public health program planning and implementation. METHODS: This study used a narrative approach, where teams from two public health units in Ontario, Canada were conveniently selected. Respondents participated in individual interviews and focus groups at each site. Questions were designed to understand the role of tacit knowledge as it related to the program planning process. Data were analyzed through a combination of content analysis and thematic comparison. RESULTS: The findings highlighted two major aspects of knowledge that arose: the use of tacit knowledge and the integration of tacit and explicit knowledge. Tacit knowledge included: past experiences, organization-specific knowledge, community contextual knowledge, and the recognition of the tacit knowledge of others. Explicit knowledge included: research literature, the Internet, popular magazines, formal assessments (surveys and interviews), legislation and regulations. Participants sometimes deliberately combined tacit and explicit knowledge sources in planning. CONCLUSIONS: This pilot demonstrated that front-line public health workers draw upon both tacit knowledge and explicit knowledge in their everyday lived reality. Further, tacit knowledge plays an important role in practitioners\u27 interpretation and implementation of explicit research findings. This indicates a need to broaden the scope of knowledge translation to include other forms of knowledge beyond explicit knowledge acquired through research. Strategies that recognize and support the use of tacit knowledge, such as communities of practice or networks, may be important components of a comprehensive approach to knowledge translation. This study provides support for further investigation of the role of tacit knowledge in the planning and delivery of effective public health services

Clinical trial of a probiotic and herbal supplement for lung health

IntroductionDysbiosis of the gut microbiome may augment lung disease via the gut-lung axis. Proteobacteria may contribute to tissue proteolysis followed by neutrophil recruitment, lung tissue injury, and perpetuation of chronic inflammation. To study the effects of probiotics across the gut-lung axis, we sought to determine if a Lactobacillus probiotic and herbal blend was safe and well-tolerated in healthy volunteers and asthmatic patients.MethodsWe conducted a 1-month randomized, open-label clinical trial in Cork, Ireland with healthy and asthmatic patients who took the blend twice a day. The primary endpoint was safety with exploratory endpoints including quality of life, lung function, gut microbiome ecology, and inflammatory biomarkers.ResultsAll subjects tolerated the blend without adverse events. Asthmatic subjects who took the blend showed significant improvements in lung function as measured by forced expiratory volume and serum short chain fatty acid levels from baseline to Week 4. The gut microbiome of asthmatic subjects differed significantly from controls, with the most prominent difference in the relative abundance of the proteobacteria Escherichia coli. Administration of the probiotic maintained overall microbial community architecture with the only significant difference being an increase in absolute abundance of the probiotic strains measured by strain-specific PCR.ConclusionThis study supports the safety and efficacy potential of a Lactobacillus probiotic plus herbal blend to act on the gut-lung axis. However, due to the lack of a control group, a longer blinded, placebo-controlled study will be warranted to confirm the efficacy improvements observed in this trial.Clinical trial registrationhttps://clinicaltrials.gov/, identifier NCT05173168

The correlates of HIV testing and impacts on sexual behavior: evidence from a life history study of young people in Kisumu, Kenya

<p>Abstract</p> <p>Background</p> <p>HIV counseling and testing is considered an important component of HIV prevention and treatment. This paper examines the characteristics of young males and females at the time of first reported HIV test, including the influence of recent sexual partnerships, and investigates how HIV testing and the cumulative number of tests are associated with sexual behaviors within six months of testing.</p> <p>Methods</p> <p>The study uses data from a random sample of youth aged 18-24 years living in Kisumu, Kenya, who were interviewed using a 10-year retrospective life history calendar. Cox regression models were used to examine the correlates of the timing of first HIV test. Variance-correction models for unordered repeated events were employed to examine whether having an HIV test in the previous six months and the cumulative number of tests predict unsafe sexual practices in a given month.</p> <p>Results</p> <p>Sixty-four percent of females and 55% of males reported at least one HIV test in the last 10 years and 40% of females were pregnant the month of first test. Significant correlates of first HIV test included marital aspirations among non-pregnant females, unprotected sex in the previous six months among pregnant females, and concurrency in the previous six months among males. Having a recent HIV test was associated with a decreased likelihood of unprotected sex among ever-pregnant females, an increased likelihood of unprotected sex and "risky" sexual partnerships among never-pregnant females, and an increased likelihood of concurrency among males. Repeated HIV testing was associated with a lower likelihood of concurrency among males and involvement in "risky" sexual partnerships among males and never-pregnant females.</p> <p>Conclusions</p> <p>The high rate of pregnancy at first test suggests that promotion of HIV testing as part of prevention of mother-to-child transmission is gaining success. Further research is warranted to examine how and why behavior change is influenced by client- versus provider-initiated testing. The influence of different sexual partnership variables for males and females suggests that interventions to assess risk and promote testing should be gender- and relationship-specific. The findings also suggest that encouraging repeat or routine testing could potentially increase the uptake of safer sexual behaviors.</p

Effectiveness-based guidelines for the prevention of cardiovascular disease in women-2011 update: A Guideline from the American Heart Association

"Substantial progress has been made in the awareness, treatment, and prevention of cardiovascular disease (CVD) in women since the first women-specific clinical recommendations for the prevention of CVD were published by the American Heart Association (AHA) in 1999.1 The myth that heart disease is a “man's disease” has been debunked; the rate of public awareness of CVD as the leading cause of death among US women has increased from 30% in 1997 to 54% in 2009.2 The age-adjusted death rate resulting from coronary heart disease (CHD) in females, which accounts for about half of all CVD deaths in women, was 95.7 per 100 000 females in 2007, a third of what it was in 1980.3,4 Approximately 50% of this decline in CHD deaths has been attributed to reducing major risk factors and the other half to treatment of CHD including secondary preventive therapies.4 Major randomized controlled clinical trials such as the Women's Health Initiative have changed the practice of CVD prevention in women over the past decade.5 The investment in combating this major public health issue for women has been significant, as have the scientific and medical achievements. Despite the gains that have been made, considerable challenges remain. In 2007, CVD still caused ≈1 death per minute among women in the United States.6 These represent 421 918 deaths, more women's lives than were claimed by cancer, chronic lower respiratory disease, Alzheimer disease, and accidents combined.6 Reversing a trend of the past 4 decades, CHD death rates in US women 35 to 54 years of age now actually appear to be increasing, likely because of the effects of the obesity epidemic.4 CVD rates in the United States are significantly higher for black females compared with their white counterparts (286.1/100 000 versus 205.7/100 000). This disparity parallels the substantially lower rate of awareness of heart disease and stroke that has been documented among black versus white women.2,6–8 Of concern is that in a recent AHA national survey, only 53% of women said the first thing they would do if they thought they were having a heart attack was to call 9-1-1. This distressing lack of appreciation by many women for the need for emergency care for acute cardiovascular events is a barrier to optimal survival among women and underscores the need for educational campaigns targeted to women.2

Cognitive aids for people with early stage dementia versus treatment as usual (Dementia Early Stage Cognitive Aids New Trial (DESCANT)): study protocol for a randomised controlled trial

Background: There is a growing need for an evidence-based approach to home support for people with dementia and their carers following diagnosis but research on the effectiveness and cost-effectiveness of different approaches is sparse. The Dementia Early Stage Cognitive Aids New Trial (DESCANT) will evaluate the clinical and costeffectiveness of a range of memory aids, training and support to people with mild to moderate dementia and their carers at home and compares that intervention with treatment as usual.Methods/design: This is a multi-site, pragmatic randomised trial preceded by a feasibility study and internal pilot. We aim to allocate at random 360 pairs comprising a person with mild to moderate dementia and an identified carer between the DESCANT intervention and treatment as usual. We assess participants at baseline, 13 and 26 weeks. The primary outcome measure is the Bristol Activities of Daily Living Scale; other participant outcomes include cognition, quality of life, activities of daily living and social networking; carer outcomes include quality of life, sense of competence and mental health. To enhance this quantitative evaluation we are conducting a qualitative component and a process evaluation to assess the implementation process and identify contextual factors associated with variation.Discussion: The DESCANT intervention reflects current policy to enhance the capabilities of people with dementia after diagnosis and their carers. If it is clinically and cost-effective, its modest nature and cost will enhance the likelihood of it being incorporated into mainstream practice.Trial registration: Current Controlled Trials, ISRCTN12591717. Registered on 29 July 2016.Protocol number: 31288: North West - Haydock Research Ethics Committee, 20/06/2016, ref.: 16/NW/0389

Discutindo a educação ambiental no cotidiano escolar: desenvolvimento de projetos na escola formação inicial e continuada de professores

A presente pesquisa buscou discutir como a Educação Ambiental (EA) vem sendo trabalhada, no Ensino Fundamental e como os docentes desta escola compreendem e vem inserindo a EA no cotidiano escolar., em uma escola estadual do município de Tangará da Serra/MT, Brasil. Para tanto, realizou-se entrevistas com os professores que fazem parte de um projeto interdisciplinar de EA na escola pesquisada. Verificou-se que o projeto da escola não vem conseguindo alcançar os objetivos propostos por: desconhecimento do mesmo, pelos professores; formação deficiente dos professores, não entendimento da EA como processo de ensino-aprendizagem, falta de recursos didáticos, planejamento inadequado das atividades. A partir dessa constatação, procurou-se debater a impossibilidade de tratar do tema fora do trabalho interdisciplinar, bem como, e principalmente, a importância de um estudo mais aprofundado de EA, vinculando teoria e prática, tanto na formação docente, como em projetos escolares, a fim de fugir do tradicional vínculo “EA e ecologia, lixo e horta”.Facultad de Humanidades y Ciencias de la Educació