Medicine and Health Sciences Commons^™

Evidence-Based Toxicology For The 21st Century: Opportunities And Challenges, Martin L. Stephens, Melvin E. Andersen, Richard A. Becker, Kellyn Betts, Kim Boekelheide, Ed Carney, Robert Chapin, Dennis Devlin, Suzanne C. Fitzpatrick, John R. Fowle Iii, Patricia Harlow, Thomas Hartung, Sebastian Hoffman, Michael P. Holsapple, Abigail Jacobs, Richard Judson, Olga Naidenko, Tim Pastoor, Grace Patlewicz, Andrew Rowan, Roberta Scherer, Rashid Shaikh, Ted Simon, Douglas Wolf, Joanne Zurlo

Martin Stephens, PhD

The Evidence-based Toxicology Collaboration (EBTC) was established recently to translate evidence-based approaches from medicine and health care to toxicology in an organized and sustained effort. The EBTC held a workshop on “Evidence-based Toxicology for the 21st Century: Opportunities and Challenges” in Research Triangle Park, North Carolina, USA on January 24-25, 2012. The presentations largely reflected two EBTC priorities: to apply evidence-based methods to assessing the performance of emerging pathwaybased testing methods consistent with the 2007 National Research Council report on “Toxicity Testing in the 21st Century” as well as to adopt a governance structure and work processes to move that …

Adaptation Of The Systematic Review Framework To The Assessment Of Toxicological Test Methods: Challenges And Lessons Learned With The Zebrafish Embryotoxicity Test, Martin L. Stephens, Sevcan Gül Akgün-Ölmez, Sebastian Hoffman, Rob De Vries, Burkhard Flick, Thomas Hartung, Manoj Lalu, Alexandra Maertens, Hilda Witters, Robert Wright, Katya Tsaioun

Martin Stephens, PhD

Systematic review methodology is a means of addressing specific questions through structured, consistent, and transparent examinations of the relevant scientific evidence. This methodology has been used to advantage in clinical medicine, and is being adapted for use in other disciplines. Although some applications to toxicology have been explored, especially for hazard identification, the present preparatory study is, to our knowledge, the first attempt to adapt it to the assessment of toxicological test methods. As our test case, we chose the zebrafish embryotoxicity test (ZET) for developmental toxicity and its mammalian counterpart, the standard mammalian prenatal development toxicity study, focusing the …

Bias During The Evaluation Of Animal Studies, Andrew Knight

Andrew Knight, Ph.D.

My recent book entitled The Costs and Benefits of Animal Experiments seeks to answer a key question within animal ethics, namely: is animal experimentation ethically justifiable? Or, more precisely, is it justifiable within the utilitarian cost:benefit framework that fundamentally underpins most regulations governing animal experimentation? To answer this question I reviewed more than 500 scientific publications describing animal studies, animal welfare impacts, and alternative research, toxicity testing and educational methodologies. To minimise bias I focused primarily on large-scale systematic reviews that had examined the human clinical and toxicological utility of animal studies. Despite this, Dr. Susanne Prankel recently reviewed my …

Lactulose_Management_Of_Minimal_Hepatic.13.Pdf, Donna M. Zucker Rn, Phd, Faan, Rhoda Redulla Dnp

Donna M. Zucker

Rita Dolan - Msc Healthcare Ethics & Law Rcsi 2016-18 - Dissertation (Final).Pdf, Rita Dolan

Rita Dolan

Genomic Variants Associated With Cancer-Related Fatigue: A Systematic Review, Joseph D. Tariman Phd, Sadaf Dhorajiwala Msn

Joseph D Tariman PhD, RN, ANP-BC, FAAN

The Usefulness Of Systematic Reviews Of Animal Experiments For The Design Of Preclinical And Clinical Studies, Rob B.M. De Vries, Kimberley E. Weaver, Marc T. Avey, Martin Stephens, Emily S. Sena, Marlies Leenaars

Martin Stephens, PhD

The question of how animal studies should be designed, conducted, and analyzed remains underexposed in societal debates on animal experimentation. This is not only a scientific but also amoral question. After all, if animal experiments are not appropriately designed, conducted, and analyzed, the results produced are unlikely to be reliable and the animals have in effect been wasted. In this article, we focus on one particular method to address this moral question, namely systematic reviews of previously performed animal experiments. We discuss how the design, conduct, and analysis of future (animal and human) experiments may be optimized through such systematic …

Reviewing Existing Knowledge Prior To Conducting Animal Studies, Andrew Knight

Andrew Knight, Ph.D.

Highly polarised viewpoints about animal experimentation have often prevented agreement. However, important common ground between advocates and opponents was demonstrated within a discussion forum hosted at www.research-methodology.org.uk in July–August 2008, by the independent charity, SABRE Research UK. Agreement existed that many animal studies have methodological flaws — such as inappropriate sample sizes, lack of randomised treatments, and unblinded outcome assessments — that may introduce bias and limit statistical validity. There was also agreement that systematic reviews of the human utility of animal models yield the highest quality of evidence, as their reliance on methodical and impartial methods to select significant …

Telemonitoring Can Assist In Managing Cardiovascular Disease In Primary Care: A Systematic Review Of Systematic Reviews, Renee Purcell, Susan Mcinnes, Elizabeth J. Halcomb

Susan McInnes

Background There has been growing interest regarding the impact of telemonitoring and its ability to reduce the increasing burden of chronic diseases, including chronic cardiovascular disease (CVD), on healthcare systems. A number of randomised trials have been undertaken internationally and synthesised into various systematic reviews to establish an evidence base for this model of care. This study sought to synthesise and critically evaluate this large body of evidence to inform clinicians, researchers and policy makers. Methods A systematic review of systematic reviews investigating the impact of telemonitoring interventions in the primary care management of CVD was conducted. Reviews were included …

Hostile Clinician Behaviours In The Nursing Work Environment And Implications For Patient Care: A Mixed-Methods Systematic Review, Marie Hutchinson, Debra Jackson

Associate Professor Marie Hutchinson

Background: Although there is a sizeable body of evidence regarding the nature of hostile behaviours among clinicians in the nursing workplace, what is less clear is the nature of the relationship between these behaviours and patient care. To inform the development of appropriate intervention strategies we examine the level of evidence detailing the relationships between hostile clinician behaviours and patient care. Methods: Published qualitative and quantitative studies that examined hostile clinician behaviours and patient care were included. Quality assessment, data extraction and analysis were undertaken on all included studies. The search strategy was undertaken in July and August 2011 and …

The Effect Of Season And Weather On Physical Activity: A Systematic Review, Patricia Tucker, Jason Gilliland

Trish Tucker

Objectives: This study reviewed previous studies to explore the effect of season, and consequently weather, on levels of physical activity. Study design and methods: Thirty-seven primary studies (published 1980–2006) representing a total of 291 883 participants (140 482 male and 152 085 female) from eight different countries are described, and the effect of season on moderate levels of physical activity is considered. Results: Upon review of the evidence, it appears that levels of physical activity vary with seasonality, and the ensuing effect of poor or extreme weather has been identified as a barrier to participation in physical activity among various …

Incubation Periods Of Viral Gastroenteritis: A Systematic Review, Rachel M. Lee, Justin Lessler, Rose A. Lee, Kara E. Rudolph, Nicholas G. Reich, Trish M. Perl, Derek A. T. Cummings

Nicholas G Reich

Background: Accurate knowledge of incubation period is important to investigate and to control infectious diseases and their transmission, however statements of incubation period in the literature are often uncited, inconsistent, and/or not evidence based. Methods: In a systematic review of the literature on five enteric viruses of public health importance, we found 256 articles with incubation period estimates, including 33 with data for pooled analysis. Results: We fit a log-normal distribution to pooled data and found the median incubation period to be 4.5 days (95% CI 3.9-5.2 days) for astrovirus, 1.2 days (95% CI 1.1-1.2 days) for norovirus genogroups I …

Predictors Of Potentially Avoidable Emergency Department Visits: A Systematic Review, Lisa M. Lines, Arlene S. Ash

Lisa M. Lines

Potentially avoidable, or primary care sensitive, emergency department (PCS ED) visits include non-emergencies and problems that potentially could have been prevented with better primary care. Our goal was to summarize the literature on the predictors of PCS ED visits. A total of 16 articles met all inclusion criteria. Characteristics found to predict PCS ED use included being female, African American, and/or covered by Medicaid. Studies defined a PCS ED visit in various ways, complicating the question of how best to prevent such visits. We identified several gaps in the literature, including lack of recent, nationally representative data; little clarity on …

Body Composition, Physical Fitness, Functional Performance, Quality Of Life, And Fatigue Benefits Of Exercise For Prostate Cancer Patients: A Systematic Review, Justin W. L. Keogh, Roderick D. Macleod

Justin Keogh

Context: Prostate cancer patients, especially those on androgen deprivation therapy (ADT), experience many symptoms that make it difficult to maintain their independence and quality of life. Because ADT acts by means of reducing testosterone production, exercise may offset many of the ADT side effects and those of the cancer itself.Objectives: This systematic review of the literature evaluates whether exercise could reduce symptoms and improve quality of life for prostate cancer patients.Methods: Using relevant databases and key words, 12 training studies were found meeting the inclusion and exclusion criteria.Results: Grade A level evidence was observed for the benefits of exercise in …

The Effect Of St John’S Wort Extracts On Cyp3a: A Systematic Review Of Prospective Clinical Trials, Hans Wohlmuth, Jason Hawrelak, Dawn Whitten, Stephen Myers

Dr Hans Wohlmuth

Aim The aim of this systematic review was to assess the quality and outcomes of clinical trials investigating the effect of St John’s wort extracts on the metabolism of drugs by CYP3A. Methods Prospective clinical trials assessing the effect of St John’s wort (SJW) extracts on metabolism by CYP3A were identified through computer-based searches (from their inception to May 2005) of Medline, Cinahl, PsycINFO, AMED, Current Contents and Embase, hand-searches of bibliographies of relevant papers and consultation with manufacturers and researchers in the field. Two reviewers selected trials for inclusion, independently extracted data and recorded details on study design. Results …

The Alvarado Score For Predicting Acute Appendicitis: A Systematic Review., Robert Ohle, Fran O'Reilly, Kirsty O'Brien, Tom Fahey, Borislav Dimitrov

Borislav D Dimitrov

BACKGROUND:

The Alvarado score can be used to stratify patients with symptoms of suspected appendicitis; the validity of the score in certain patient groups and at different cut points is still unclear. The aim of this study was to assess the discrimination (diagnostic accuracy) and calibration performance of the Alvarado score.

METHODS:

A systematic search of validation studies in Medline, Embase, DARE and The Cochrane library was performed up to April 2011. We assessed the diagnostic accuracy of the score at the two cut-off points: score of 5 (1 to 4 vs. 5 to 10) and score of 7 (1 …

The Effectiveness Of Post-Operative Rehabiliation Following Partial Meniscectomy Of The Knee, Duncan Reid, Jana Rydwanski, Wayne Hing, Steve White

Wayne Hing

Background: Injuries to the menisci of the knee are a common cause of impairment and functional disability. The prevalence of meniscal injury ranges from 19 to 56% depending on the population studied. Arthroscopic surgery to the meniscus may be required if conservative care has failed. There is still controversy as to the need for routine post-operative rehabilitation to improve function and reduce impairments.

Objectives: The purpose of this paper was to systematically review the literature that evaluated the effectiveness of post-operative exercise programmes to improve function and reduce impairments following partial meniscectomy of the knee.

Methods: A computerized electronic search …

Patterns Of 'Leakage' In The Utilisation Of Clinical Guidelines: A Systematic Review, Sharon Mickan, Amanda Burls, Paul Glasziou

Paul Glasziou

Background Research: Evidence is insufficient to change physicians’ behaviour. In 1996, Pathman developed a four step model: that physicians need to be aware of, agree with, adopt, and adhere to guidelines. Objective: To review evidence in different settings on the patterns of ‘leakage’ in the utilisation of clinical guidelines using Pathman’s awareness-to-adherence model.Methods: A systematic review was conducted in June 2010. Primary studies were included if they reported on rates of awareness and agreement and adoption and/or adherence.Results: 11 primary studies were identified, reporting on 29 recommendations. Descriptive analyses of patterns and causes of leakage were tabulated and graphed. Leakage …

Does Inorganic Mercury Play A Role In Alzheimer's Disease? A Systematic Review And An Integrated Molecular Mechanism, Joachim Mutter, Annika Curth, Johannes Naumann, Richard Deth, Harald Walach

Richard Deth

Mercury is one of the most toxic substances known to humans. It has been introduced into the human environment and has also been widely used in medicine. Since circumstantial evidence exists that the pathology of Alzheimer’s disease (AD) might be in part caused or exacerbated by inorganic mercury, we conducted a systematic review using a comprehensive search strategy. Studies were screened according to a predefined protocol. Two reviewers extracted relevant data independent of each other. One thousand and forty one references were scrutinized, and 106 studies fulfilled the inclusion criteria. Most studies were case control or comparative cohort studies. Thirty-two …

Letter: "Drink Plenty Of Fluids" Authors' Reply, Michelle P. B. Guppy, Sharon M. Mickan, Chris Del Mar

Christopher Del Mar

"Drink plenty of fluids" - Recommendations are not supported by data - [Authors' reply]. Let us look deeper at the indirect evidence. Two case reports describe children with only infections of the upper respiratory tract with hyponatraemia and seizures. In infections of the lower respiratory tract, observational studies show that increased secretion of antidiuretic hormone occurs in bronchiolitis, where it is the norm. It is becoming standard management to advise careful monitoring and restriction of fluid intake with bronchiolitis.

"Drink Plenty Of Fluids": A Systematic Review Of Evidence For This Recommendation In Acute Respiratory Infections, Michelle P. B. Guppy, Sharon M. Mickan, Chris Del Mar

Christopher Del Mar

Doctors often recommend drinking extra fluids to patients with respiratory infections. Theoretical benefits for this advice are replacing insensible fluid losses from fever and respiratory tract evaporation, correcting dehydration from reduced intake, and reducing the viscosity of mucus. However there are theoretical reasons for increased fluid intake to cause harm. Giving extra fluids while antidiuretic hormone secretion is increased (reported in some lower respiratory tract infections) may theoretically lead to hyponatraemia and fluid overload. Despite a systematic review to determine whether recommending increased fluids was beneficial or harmful no randomised controlled trials comparing increased and restricted fluid regimens in patients …

Systematic Review And Individual Patient Data Meta-Analysis Of Diagnosis Of Heart Failure, With Modelling Of Implications Of Different Diagnostic Strategies In Primary Care, J. Mant, J. Doust, A. Roalfe, P. Barton, M. Cowie, P. Glasziou, D. Mant, R. Mcmanus, R. Holder, J. Deeks, K. Fletcher, M. Qume, S. Sohanpal, S. Sanders, F. Hobbs

Jenny Doust

Objectives: To assess the accuracy in diagnosing heart failure of clinical features and potential primary care investigations, and to perform a decision analysis to test the impact of plausible diagnostic strategies on costs and diagnostic yield in the UK health-care setting. Data sources: MEDLINE and CINAHL were searched from inception to 7 July 2006. ‘Grey literature’ databases and conference proceedings were searched and authors of relevant studies contacted for data that could not be extracted from the published papers. Review methods: A systematic review of the clinical evidence was carried out according to standard methods. Individual patient data (IPD) analysis …

Worldwide Variation In The Doubling Time Of Alzheimer's Disease Incidence Rates, Kathryn Ziegler-Graham, Ron Brookmeyer, Elizabeth Johnson, H. Michael Arrighi

Ron Brookmeyer

Background The doubling time is the number of chronological years for the age-specific incidence rate to double in magnitude. Doubling times describe the rate of increase of the risk of Alzheimer's disease (AD) with advancing age. Estimates of doubling times of AD assist in understanding disease etiology and forecasting future disease prevalence. The objective of this study was to investigate regional and gender differences in the doubling of AD age-specific incidence rates.

Methods We identified all studies in the peer review literature that reported age-specific incidence rates for AD. We modeled the logarithm of the incidence rate as a linear …

Doctors As Patients: A Systematic Review Of Doctors' Health Access And The Barriers They Experience, Margaret Kay, Geoffrey Mitchell, Alexandra Clavarino, Jenny Doust

Jenny Doust

Background The need to improve doctors' access to health care by reducing the barriers they experience has been regularly described in the literature, yet the barriers experienced are not well defined, despite the volume of expert opinion in this area. Aim To define what is known about doctors' access to health care from the data within the current literature.Design of study A systematic review of studies of doctors' health access.Method A systematic search of MEDLINE® and CINAHL, supplemented by citation searches and searches of the grey literature, identified both quantitative and qualitative studies. Two reviewers used specific criteria for inclusion …