Evidence-based Interpretation Research Articles

Evidence-based Interpretation of Amyloid-β PET Results: A Clinician's Tool.

Amyloid-β positron emission tomography (PET) allows for in vivo detection of fibrillar amyloid plaques, a pathologic hallmark of Alzheimer's disease (AD). However, amyloid-β PET interpretation is limited by the imperfect correlation between PET and autopsy, and the fact that it is positive in about 20% to 30% of cognitively normal individuals and non-AD dementias, especially when older or carrying the ε4 allele of apolipoprotein E (ApoE4). When facing a positive amyloid PET, clinicians have to evaluate the probability of a pathologic false positive as well as the probability of amyloid positivity being age-related, comorbid to a primary non-AD dementia (clinicopathologic false positive). These probabilities can be calculated to reach an evidence-based interpretation of amyloid-β. As literature review and calculations cannot be easily performed in the day-to-day clinic, we propose a clinician friendly, evidence-based Bayesian approach to the interpretation of amyloid-β PET results in the differential diagnosis of patients with cognitive impairment. We defined AD as a clinicopathologic entity in which amyloid-β is the primary cause of cognitive impairment. We systematically reviewed the literature to estimate the sensitivity and specificity of amyloid-β PET against neuropathologic examination. We inferred rates of clinicopathologic false positivity (non-AD dementia with comorbid amyloid) based on age-dependent and ApoE-dependent prevalence of amyloid positivity in normal individuals and AD patients provided in large meta-analyses published by the Amyloid Biomarker Study Group. We calculated positive predictive value (PPV) and negative predictive value (NPV) of amyloid-β PET, which are presented in a clinician-friendly table. PPV of PET is highest in young ApoE4- patients with high pre-PET probability of AD. In older ApoE4+ patients with low pre-PET probability of AD, positive amyloid-β PET scans must be interpreted with caution. A negative amyloid-β PET makes a diagnosis of AD unlikely except in old patients with high pre-PET probability of AD. This evidence-based approach might provide guidance to clinicians and nuclear medicine physicians to interpret amyloid-β PET results for early and differential diagnosis of patients with progressive cognitive impairment.

Memantine as an Augmentation Treatment for Schizophrenia: Limitations of Meta-Analysis for Evidence-Based Evaluation of Research.

The action of memantine on N-methyl-D-aspartate (NMDA) glutamatergic receptors and the other pharmacodynamic actions of this drug suggest that it may benefit patients with schizophrenia. Many randomized controlled trials (RCTs) have examined this possibility. These RCTs have been meta-analyzed by at least 2 groups of authors. In one meta-analysis (8 RCTs, pooled N = 448), memantine (20 mg/d for 6-12 weeks) augmentation of antipsychotic drug therapy was found to attenuate the severity of negative symptoms and improve cognitive functioning; in both regards, the effect was large. Memantine was also associated with a small but statistically significant reduction in general psychopathology. Whereas memantine did not significantly attenuate positive symptom, depression, total psychopathology, and global illness ratings, it was also not associated with an increased risk of individual adverse events, discontinuation due to adverse events, or all-cause discontinuation. The findings of the other meta-analysis, which examined much the same body of literature, were largely similar. On the surface, these results suggest that memantine may be considered for the reduction of negative symptoms and cognitive impairment in schizophrenia. However, an examination of the individual RCTs and a careful look at the findings of the meta-analyses identify so many important concerns that it is probably premature to draw conclusions about the usefulness of memantine as an augmentation strategy in schizophrenia. At best, it may be stated that there is a signal that supports the study of memantine in schizophrenia patients who are specifically impaired by negative symptoms and cognitive complaints. This is a good example of a situation in which meta-analysis did not provide a trustable evidence-based interpretation of literature.

Avoidable drug-gene conflicts and polypharmacy interactions in patients participating in a personalized medicine program.

Determine the ability of a pharmacogenetic service, PRIMER, to identify drug-gene (DGI) and drug-drug interactions (DDI) in patients across multiple conditions. PRIMER consists of patient selection criteria, a gene panel and actionable guidance for DGIs and DDIs. The average patient was prescribed 12 medications. PRIMER identified significant DGIs in 73% of patients tested, with 43% having more than one DGI. DDIs were found in 87% of patients. The most common actionable DGIs were for opioid, psychotropic and cardiovascular medications. The pairing of patient selection criteria, a multigene panel with evidence-based interpretation and review of DDIs maximizes the patients tested who have actionable benefit and alerts physicians to potentially critical adjustments needed for the patient's medication regimen.

Операционализация контекста в дискурсивном анализе

The author puts the notion of context under the analytical spotlight. The context is discussed as a sociocultural dimension of a text structure. It is presumed that context is one of the most elusive notions in social sciences resisting formalization. The question of how to indicate and define extralinguistic aspects relevant in explanation of text meanings is a key issue both in modern text linguistics and discourse linguistics. In a broader dimension, it might contribute to evidence-based interpretation of linguistic facts.This paper will follow the idea that operationalization of a context is not to be reduced to a communicative situation, some kind of social environment of a text, but is to be explained as a discursive competence of language speakers sharing social practice and cognitive framework. It is the social practice that causes and effects operationalization of relevant context aspects and thus the adequate understanding of text meanings. It is presumed that a cognitive representation of context in the mind of those involved in communication is analytically relevant. To perform an adequate analysis of discourse, we need to include a cognitive dimension. To operationalize context means to take into consideration features of actual practice in specific cultural, historical etc. conditions. The discursive competence controls all the relevant aspects of the production and comprehension of discourse that vary with the social situation. In this aspect, the author critically discusses the main thesis of T. van Dijk’s conception that interpretation by the participants of the relevant dimensions of the social environment is represented in so-called “context models” in episodic memory.The article discusses the extent to which different extralinguistic factors can be effectively used in noncritical discourse analysis and in critical discourse analysis / CDA, it discusses the merits and explana­tory potential of CDA.

Textural features of 18F-fluorodeoxyglucose positron emission tomography scanning in diagnosing aortic prosthetic graft infection

BackgroundThe clinical problem in suspected aortoiliac graft infection (AGI) is to obtain proof of infection. Although 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography scanning (PET) has been suggested to play a pivotal role, an evidence-based interpretation is lacking. The objective of this retrospective study was to examine the feasibility and utility of 18F-FDG uptake heterogeneity characterized by textural features to diagnose AGI.MethodsThirty patients with a history of aortic graft reconstruction who underwent 18F-FDG PET/CT scanning were included. Sixteen patients were suspected to have an AGI (group I). AGI was considered proven only in the case of a positive bacterial culture. Positive cultures were found in 10 of the 16 patients (group Ia), and in the other six patients, cultures remained negative (group Ib). A control group was formed of 14 patients undergoing 18F-FDG PET for other reasons (group II). PET images were assessed using conventional maximal standardized uptake value (SUVmax), tissue-to-background ratio (TBR), and visual grading scale (VGS). Additionally, 64 different 18F-FDG PET based textural features were applied to characterize 18F-FDG uptake heterogeneity. To select candidate predictors, univariable logistic regression analysis was performed (α = 0.16). The accuracy was satisfactory in case of an AUC > 0.8.ResultsThe feature selection process yielded the textural features named variance (AUC = 0.88), high grey level zone emphasis (AUC = 0.87), small zone low grey level emphasis (AUC = 0.80), and small zone high grey level emphasis (AUC = 0.81) most optimal for distinguishing between groups I and II. SUVmax, TBR, and VGS were also able to distinguish between these groups with AUCs of 0.87, 0.78, and 0.90, respectively. The textural feature named short run high grey level emphasis was able to distinguish group Ia from Ib (AUC = 0.83), while for the same task the TBR and VGS were not found to be predictive. SUVmax was found predictive in distinguishing these groups, but showed an unsatisfactory accuracy (AUC = 0.75).ConclusionTextural analysis to characterize 18F-FDG uptake heterogeneity is feasible and shows promising results in diagnosing AGI, but requires additional external validation and refinement before it can be implemented in the clinical decision-making process.

Reading Objects

AbstractObject-based, experiential learning/evidence-based inquiry engages young minds and models how research is conducted. It is clear that this kind of authentic experience stays with students long afterward. Our research investigated 74 fifth-grade public school students’ conceptions of evidence, of the provisional nature of archaeological and historical interpretations, and of the purposes for using archaeology to study the past. Three and four years later, we conducted follow-up interviews with 29 of the students to investigate what they remembered about their archaeological experience, including classroom instruction, excavation/labwork, and concepts related to archaeological processes and historical information. Our study shows that in-depth archaeological study has considerable sticking power. It also provides important insights into how students think about archaeology, history, and the past, and how they relate “things” to the past and to past cultures. In particular, it shows that the materiality of archaeology offers students opportunities to create multiple, evidence-based interpretations when they are taught to understand culture in material ways. Our study also offers concrete suggestions for anyone considering using objects to teach about the past: use an inquiry-based approach, take students’ prior knowledge into account, use metaphors carefully with younger children, and make the human-object connection explicit for all.

Mathematical Analysis of Historical Income Per Capita Distributions

Abstract. Data describing historical growth of income per capita [Gross Domestic Product per capita (GDP/cap)] for the world economic growth and for the growth in Western Europe, Eastern Europe, Asia, former USSR, Africa and Latin America are analysed. They follow closely the linearly-modulated hyperbolic distributions represented by the ratios of hyperbolic distributions obtained by fitting the GDP and population data. Results of this analysis demonstrate that income per capita was increasing monotonically . There was no stagnation and there were no transitions from stagnation to growth. The usually postulated dramatic escapes from the Malthusian trap never happened because there was no trap in the economic growth. Unified Growth Theory is fundamentally incorrect because its central postulates are contradicted repeatedly by data, which were used but never analysed during the formulation of this theory. The large body of readily-available data opens new avenues for the economic and demographic research. They show that certain fundamental postulates revolving around the concept of Malthusian stagnation need to be replaced by the evidence-based interpretations. Within the range of analysable data, which for the growth of population extends down to 10,000 BC, growth of human population and economic growth were hyperbolic. There was no Malthusian stagnation and there were no transitions to distinctly faster trajectories. Industrial Revolution had no impact on changing growth trajectories. Keywords. Economic growth, Income per capita, Unified Growth Theory, Hyperbolic growth, Industrial Revolution, Takeoffs, Malthusian stagnation JEL. A10 , C12, C20, C50, F00.

Longitudinal qualitative exploration of cancer information-seeking experiences across the disease trajectory: the INFO-SEEK protocol

IntroductionΑ substantial corpus of literature has sought to describe the information-seeking behaviour of patients with cancer. Yet, available evidence comes mainly from cross-sectional studies, which provide ‘snapshots’ of patients’ information...

Inventing the Neolithic? Putting evidence-based interpretation back into the study of faunal remains from causewayed enclosures

The paper argues that our current understanding of the animal bones from causewayed enclosure sites in Britain is flawed. During the 1980–90s, a number of key interpretations, still frequently espoused, were based more upon anecdote and theory-driven assertion than on empirical evidence. An example is that evidence of bone processing (butchery and bone fracture) does not feature heavily in the faunal record from causewayed enclosures. Using data from the sites of Etton and Staines, this view must now be questioned. Both butchery and peri-mortem bone fracture are present in these assemblages in substantial quantities. These sites are compared with Ludwinowo 7, a Linearbandkeramik settlement site in Poland and there are considerable similarities between the three different sites. This suggests possibility that the broader economic utility of animal bone assemblages at causewayed enclosures has been underestimated, having been, up to now, regarded as ‘not indicative of domestic settlement’.

Semantic interoperability in healthcare.

The improved understanding of the whole healthcare and wellbeing pathway for individuals depends on the power of healthcare information, being made readily available and easily interpretable by both humans and machines. In the centre of this challenge lies the concept of interoperability, as a way to provide fundamental linkage, integration and meaningful use of healthcare data between systems, organisations and users. In particular, semantic interoperability can offer a way of enriching healthcare data with context and meaning, in order to achieve enhanced understanding and better evidence-based interpretation of disease and wellbeing for an individual, within the context of healthcare provision and clinical research. In this keynote paper, the concept of semantic interoperability, for healthcare data linkage and exchange, is critically discussed. An emphasis is given on the importance of clinical terminologies and associated services, as means for adding meaning to routinely collected clinical data.

The first step in Data Analysis: Transcribing and managing qualitative research data

AbstractResearchers need to take data from the spoken text (structured, unstructured, or narrative interviews) to written form for analysis. Typically this is handled through deidentifying the participants and transcribing the data, and is considered the first step in analysis. The accuracy of the transcription plays a role in determining the accuracy of the data that are analyzed and with what degree of dependability. Analysis begins after reviewing the first interview to examine whether participants are responding to the research question related to your area of interest in diabetes, or whether your interview guide needs refining. As each interview is completed, the researcher examines its content to determine what has been learned and what still needs to be discovered or needs elaboration. Moving from raw interviews to evidence-based interpretations requires preparing transcripts so they will be ready to code. Before moving directing to analysis (or coding), it is important to recognize the task of handling the qualitative research data during and after the interview. This paper describes the process of transcription and handling the qualitative data related to diabetes research.

Postanalytical tools improve performance of newborn screening by tandem mass spectrometry.

Purpose:The purpose of this study was to compare performance metrics of postanalytical interpretive tools of the Region 4 Stork collaborative project to the actual outcome based on cutoff values for amino acids and acylcarnitines selected by the California newborn screening program.Methods:This study was a retrospective review of the outcome of 176,186 subjects born in California between 1 January and 30 June 2012. Raw data were uploaded to the Region 4 Stork Web portal as .csv files to calculate tool scores for 48 conditions simultaneously using a previously unpublished functionality, the tool runner. Scores for individual target conditions were deemed informative when equal or greater to the value representing the first percentile rank of known true-positive cases (17,099 cases in total).Results:In the study period, the actual false-positive rate and positive predictive value were 0.26 and 10%, respectively. Utilization of the Region 4 Stork tools, simple interpretation rules, and second-tier tests could have achieved a false-positive rate as low as 0.02% and a positive predictive value >50% by replacing the cutoff system with Region 4 Stork tools as the primary method for postanalytical interpretation.Conclusion:Region 4 Stork interpretive tools, second-tier tests, and other evidence-based interpretation rules could have reduced false-positive cases by up to 90% in California.

The Beauty of Other Lives: Material Culture as Evidence of Human Ingenuity and Agency

Elementary students are often hampered by a tendency to ascribe innovation to increasing human intelligence or individual agency rather than increased information, better access to information, or collective and institutional agency. As a result, they struggle to build evidence-based interpretations of the distant past. A fifth-grade “experimental archaeology” approach to studying ancient Eastern Woodlands Indians served as an intellectual tipping point in students' interpreting ancient people's intellect, ingenuity, and agency. As fifth-graders participated in a field-based experience with chaîne opératoire (the sequence of operations) for tools and technologies, classroom-based opportunities to consider material objects as primary sources, and opportunities for reflection, they confirmed the power of “engaged understanding” in supporting the humanistic and civic goals of social studies.

Lower urinary tract development and disease.

Congenital anomalies of the lower urinary tract (CALUT) are a family of birth defects of the ureter, the bladder, and the urethra. CALUT includes ureteral anomaliesc such as congenital abnormalities of the ureteropelvic junction (UPJ) and ureterovesical junction (UVJ), and birth defects of the bladder and the urethra such as bladder-exstrophy-epispadias complex (BEEC), prune belly syndrome (PBS), and posterior urethral valves (PUVs). CALUT is one of the most common birth defects and is often associated with antenatal hydronephrosis, vesicoureteral reflux (VUR), urinary tract obstruction, urinary tract infections (UTI), chronic kidney disease, and renal failure in children. Here, we discuss the current genetic and molecular knowledge about lower urinary tract development and genetic basis of CALUT in both human and mouse models. We provide an overview of the developmental processes leading to the formation of the ureter, the bladder, and the urethra, and different genes and signaling pathways controlling these developmental processes. Human genetic disorders that affect the ureter, the bladder and the urethra and associated gene mutations are also presented. As we are entering the postgenomic era of personalized medicine, information in this article may provide useful interpretation for the genetic and genomic test results collected from patients with lower urinary tract birth defects. With evidence-based interpretations, clinicians may provide more effective personalized therapies to patients and genetic counseling for their families.

Integration of Genomic Medicine into Pathology Residency Training: The Stanford Open Curriculum

Next-generation sequencing methods provide an opportunity for molecular pathology laboratories to perform genomic testing that is far more comprehensive than single-gene analyses. Genome-based test results are expected to develop into an integral component of diagnostic clinical medicine and to provide the basis for individually tailored health care. To achieve these goals, rigorous interpretation of high-quality data must be informed by the medical history and the phenotype of the patient. The discipline of pathology is well positioned to implement genome-based testing and to interpret its results, but new knowledge and skills must be included in the training of pathologists to develop expertise in this area. Pathology residents should be trained in emerging technologies to integrate genomic test results appropriately with more traditional testing, to accelerate clinical studies using genomic data, and to help develop appropriate standards of data quality and evidence-based interpretation of these test results. We have created a genomic pathology curriculum as a first step in helping pathology residents build a foundation for the understanding of genomic medicine and its implications for clinical practice. This curriculum is freely accessible online.

Abstract No. 311: Evidence-based medicine research and interpretation: avoiding the pitfalls

Abstract No. 311: Evidence-based medicine research and interpretation: avoiding the pitfalls

Sexual Abuse

Child sexual abuse is a common pediatric problem that concerns all pediatric health care providers. Management of child sexual abuse is multifaceted and multidisciplinary. Specialized health providers can provide consultation, but this availability does not minimize the role of the referring physician who often has ongoing contact with the family. Physicians are mandated to report cases of suspected or confirmed sexual abuse. In the majority of cases, a child’s statement about sexual abuse is the strongest evidence that abuse has occurred. Physical examination is normal in the majority of sexual abuse victims. Accurate, evidence-based interpretation of physical and laboratory findings is essential. Normal examinations, normal variants, and findings indicative of sexual contact must be differentiated. Forensic evidence collection and prophylactic treatments may be indicated when patients present within 72 hours of an abusive episode, and patients should be triaged accordingly. Potentially negative psychosocial outcomes should be addressed for patients and their families on initial evaluation and follow-up.

The Dilated Distal Esophagus

Present management algorithms for patients with gastroesophageal reflux disease (GERD) limit endoscopy to patients with advanced disease. When endoscopy is performed, biopsy is limited to patients who have a visible columnar-lined esophagus. Biopsy is not recommended for patients whose endoscopy is normal. This algorithm results in the failure to evaluate patients with early stages of GERD at a pathologic level. We report 714 patients with normal endoscopic findings irrespective of symptoms who had adequate biopsies taken from the squamocolumnar junction and the area 1-cm distal to this from mucosa that had rugal folds. Concurrent biopsies were also taken from the gastric body and/or antrum. All patients had a gap between their esophageal squamous epithelium and gastric oxyntic mucosa in the junctional region composed of oxyntocardiac ± cardiac ± intestinal epithelia. A total of 643 (90.1%) patients had no significant pathology in the gastric antrum and/or body, indicating that the squamooxyntic gap was an isolated abnormality in this region in all but 71 (9.9%) patients. The gap contained only oxyntocardiac epithelium in 71 (9.9%) patients, cardiac mucosa without intestinal metaplasia in 482 (67.5%) patients, and intestinal metaplasia in 161 (22.6%) patients. The pathologic interpretation of biopsies taken from the gastroesophageal junction is confusing and has significant interobserver variation. This results from lack of agreement as to whether these biopsies originate in the proximal stomach ("gastric cardia") or in the esophagus. We provide evidence that the presence of oxyntocardiac ± cardiac ± intestinal epithelia in biopsies from patients who are endoscopically normal is diagnostic of a dilated GERD-damaged distal esophagus. The dilated distal esophagus is the pathologic manifestation of destruction of the abdominal segment of the lower esophageal sphincter. Its presence is the pathologic basis of early GERD, which is missed if patients who are endoscopically normal are not biopsied, as is the present recommendation. Its recognition allows for accurate and evidence-based interpretation of biopsies from this region and removes the present confusion and permits the development of a reproducible pathologic diagnostic method.

Meta-analysis provides evidence-based interpretation guidelines for the clinical significance of mean differences for the FACT-G, a cancer-specific quality of life questionnaire

Our aim was to develop evidence-based interpretation guidelines for the Functional Assessment of Cancer Therapy-General (FACT-G), a cancer-specific health-related quality of life (HRQOL) instrument, from a range of clinically relevant anchors, incorporating expert judgment about clinical significance. Three clinicians with many years’ experience managing cancer patients and using HRQOL outcomes in clinical research reviewed 71 papers. Blinded to the FACT-G results, they considered the clinical anchors associated with each FACT-G mean difference, predicted which dimensions of HRQOL would be affected, and whether the effects would be trivial, small, moderate, or large. These size classes were defined in terms of clinical relevance. The experts’ judgments were then linked with FACT-G mean differences, and inverse-variance weighted mean differences were calculated for each size class. Small, medium, and large differences (95% confidence interval) from 1,118 cross-sectional comparisons were as follows: physical well-being 1.9 (0.6–3.2), 4.1 (2.7–5.5), 8.7 (5.2–12); functional well-being 2.0 (0.5–3.5), 3.8 (2.0–5.5), 8.8 (4.3–13); emotional well-being 1.0 (0.1–2.6), 1.9 (0.3–3.5), no large differences; social well-being 0.7 (−0.7 to 2.1), 0.8 (−2.9 to 4.5), no large differences. Results from 436 longitudinal comparisons tended to be smaller than the corresponding cross-sectional results. These results augment other interpretation guidelines for FACT-G with information on sample size, power calculations, and interpretation of cancer clinical trials that use FACT-G.

Compliance assessment of ambulatory Alzheimer patients to aid therapeutic decisions by healthcare professionals

BackgroundCompliance represents a major determinant for the effectiveness of pharmacotherapy. Compliance reports summarising electronically compiled compliance data qualify healthcare needs and can be utilised as part of a compliance enhancing intervention. Nevertheless, evidence-based information on a sufficient level of compliance is scarce complicating the interpretation of compliance reports. The purpose of our pilot study was to determine the compliance of ambulatory Alzheimer patients to antidementia drugs under routine therapeutic use using electronic monitoring. In addition, the forgiveness of donepezil (i.e. its ability to sustain adequate pharmacological response despite suboptimal compliance) was characterised and evidence-based guidance for the interpretation of compliance reports was intended to be developed.MethodsWe determined the compliance of four different antidementia drugs by electronic monitoring in 31 patients over six months. All patients were recruited from the gerontopsychiatric clinic of a university hospital as part of a pilot study. The so called medication event monitoring system (MEMS) was employed, consisting of a vial with a microprocessor in the lid which records the time (date, hour, minute) of every opening. Daily compliance served as primary outcome measure, defined as percentage of days with correctly administered doses of medication. In addition, pharmacokinetics and pharmacodynamics of donepezil were simulated to systematically assess therapeutic undersupply also incorporating study compliance patterns. Statistical analyses were performed with SPSS and Microsoft Excel.ResultsMedian daily compliance was 94% (range 48%-99%). Ten patients (32%) were non-compliant at least for one month. One-sixth of patients taking donepezil displayed periods of therapeutic undersupply. For 10 mg and 5 mg donepezil once-daily dosing, the estimated forgiveness of donepezil was 80% and 90% daily compliance or two and one dosage omissions at steady state, respectively. Based on the simulation findings we developed rules for the evidence-based interpretation of donepezil compliance reports.ConclusionsCompliance in ambulatory Alzheimer patients was for the first time assessed under routine conditions using electronic monitoring: On average compliance was relatively high but variable between patients. The approach of pharmacokinetic/pharmacodynamic in silico simulations was suitable to characterise the forgiveness of donepezil suggesting evidence-based recommendations for the interpretation of compliance reports.